Endocrine System and Hormone Functions (Endocrinology)

Endocrine System:

Regulatory system which interacts with the nervous system to coordinate and integrate the
activity of body cells
Hypothalamus: helps tie the two systems together (has neuro function as well as endocrine
function- produce and release hormones) I.E. its a neuroendocrine gland
Endocrine system has a slower response system (from seconds to even days) as opposed to NS
which happens in milliseconds
Major processes controlled and integrated by these hormones are: reproduction; growth and
development; maintenance of electrolyte, water, and nutrient balance of the blood; regulation
of cellular metabolization of body defenses

Endocrine Glands (ductless glands):

Produce hormones and lack ducts

Secrete their hormones into the surrounding tissue fluid (extracellular space), and are then
picked up by the bloodstream and carried to almost every cell in the body (target cells)
Have rich vascular and lymphatic drainage that receives their hormones
Endocrine glands include: Pituitary, thyroid, parathyroid, adrenal, and pineal glands,
hypothalamus, thymus, pancreas, gonads (testes and ovaries)
Other endocrine structures: small intestines and stomach, kidneys, heart, skin, placenta
Hormones are 1) chemical (structure), 2) messengers (function) (chemical substances secreted
by cells which cause a variety of physiological effect)
Autocrines: chemicals that exert their effects on the same cells that secrete them
Paracrines: act locally but affect cell types other than those releasing the paracrine chemicals

Function:

Help regulate:
Internal environments by regulating their chemical composition and volumes
Metabolism and energy balance
Contraction and relaxation of smooth and cardiac muscle fibers
Glandular production and secretion
Response to stressors, effected by marked changes in the environment
Operations of reproductive system and process: gamete production -> fertilization ->
nourishes embryo/fetus -> delivery -> controls ongoing growth and developed (for
smooth progressive integration)
Maintenance of electrolyes
Helps establish circadian rhythm (sleep/wake cycle)

Hormones:
Chemistry of Hormones

Definition: Chemical substances, secreted by cells into the extracellular fluids that regulate the
metabolic function of other cells in the body. Nearly all of them can be classified chemically as
either amino acid based or steroids
Amino Acid based molecules (H2O soluble, most common type) vary in size
Proteins, glycoprotein, polypeptides
These hormones are released from the: pituitary, parathyroid, thyroid, pancreas, and
adrenal medulla
Steroids:
Lipid soluble, steroids cholesterol, and fatty acids
Synthesized from cholesterol
Released from adrenal cortex and gonads
Eicosanoids: (highly localized-paracrines and autocrines)
Include leukotrienes and prostaglandins
Produces and released by virtually every cells membrane in the body
Regulatory chemicals: (eicosapentaenoic acids [EPA])
Biologically active lipids made from arachidonic acid- 20 carbon fatty acid
Lipoxygenase converts eicosanoids to leukotrines
o Leukotrienes: signaling chemicals that mediate inflammation and some allergic
reactions (released by activated WBCs, as in positive chemotaxis)
Cocooxygenase converts eicosanoids to prostaglandins:
o Prostaglandins: have multiple targets and effects, ranging from raising blood
pressure and increasing the expulsive uterine contraction of birth to enhancing
blood clotting, pain, and inflammation
Prostaclyin:
o Released from blood vessel walls
o Inhibits vasoconstriction and clotting
Thromboxane:
o Released from platelets for clotting and is a potent vasoconstrictor
Highly localized, dont fit true definition of hormones; act as paracrines and autocrines
Monoamines (biogenic amines)
Catacholamines (norepinephrine and epinephrine), dopamine, melatonin, thyroid
hormone

Hormone Target Cell Specificity:

1. Hormone-Receptor Bindings:
Target cells: cells that respond to a specific hormone due to specific receptors (all cells are
target cells BUT only for specific hormones)

Receptors: proteins on target cells that have a unique capacity that allows it to bind with a
specific (shape and/or chemistry) hormone
Target cell activation: the interaction of a specific R/C and hormone, which will initiate the
specific intracellular
R/C are found within the cell (in the cytoplasm/nucleus) or on the cell membrane
Hormone-R/C binding-> target cell activation-> biochemical events

2. Factors in target cell activation: as a result of hormone-R/C binding

Three factors help to determine cell activation:
1. Blood level of the hormone
2. Number of receptors the cell contains
3. The affinity (strength of the binding) for the union between hormone and R/C
Any changes of variations of these conditions will change cell/tissue response
3. Receptors are dynamic: R/Cs are subject to physiological regulations.
Phenomena called down regulation and or up regulation (due to ongoing production and
degradation of hormones, need dependent.)
Down regulation: (M/C)
o A decrease in the number of receptor molecules of the target cell
o Seen with a chronically high concentration of a specific hormone,
o target cell R/C will decrease in number,
o decrease target cell response and not allowing that cell to overproduce
Up regulation:
o An increase in the number of receptor molecules of the target cell
o Increase in response to higher levels of specific hormones
o Also seen with very low concentration of hormones because they become
supersensitive (may also help to decrease affinity)
Mechanism of Hormone Action

Will produce one or more changes biochemical events (inc. or dec. cell function), such as:
Alters plasma membrane permeability or membrane potential, or both, by opening or
closing ion channels
Stimulates synthesis of proteins or regulatory molecules such as enzymes within the cell
Activates or deactivates enzymes
Induces secretory activity
Stimulates mitosis
Hormones exert their effects on target cells in two ways:
Second messenger system: (water soluble, amino acid based)
o Interacts with a extracellular membrane-bound R/C (plasma membrane outside
of cell)
Direct gene activation: (lipid soluble, fat based/ thyroid)

o Interacts with an intracellular R/C (cytoplasm inside the cell)

Second messenger system:
1. Hormone binds receptor:
Hormone (acting as 1st messenger), bind to its receptor on the plasma membrane
2. Receptor activates G protein:
Hormone binding to receptor cause the receptor to change shape, allowing it to
bind to a nearby active G protein
G protein is like a light switch, GDP (off) and GTP (on)
3. G protein activates adenylate cyclase:
Now activated G protein moves along the membrane to the effector enzyme
(adenylate cyclase) and binds to it.
Gs stimulate adenylate cyclase and Gi inhibits adenylate cyclase
GTP bound to G protein is hydrolyzed to GDP and the G protein becomes inactive
once again
4. Adenylate cyclase converts ATP to cyclic AMP:
As long as activated Gs is bound to it, adenylate cyclase generates the second
messenger cAMP (cyclic AMP) from ATP
5. Cyclic AMP activates protein kinases:
Cyclic AMP (second messenger) will diffuse (free to diffuse) through the cell and
triggers a cascade of chemical reactions by activating protein kinase
Protein kinase: enzymes that phosphorylate (add a phosphate group to) various
proteins, many of which are other enzymes
Since phosphorylation activates some of these proteins and inhibits others, a variety
of processes may be affected in the same target cell at the same time
6. Cyclic AMP is quickly degraded by phosphodiesterase (enzyme):
due to the cascade effect and amplification there will be millions of final product
molecules; therefore, most hormones need to be present only briefly to cause the
desired result.
Some cell reactions will use a 3rd messenger Ca++, causing direct activation or by binding to
calmodulin
The opposite occurs when a different type of receptor of the target cell is activated. Ex: if an
inhibitory G protein is stimulated, it shuts off the cell

Direct gene activation:

Hormone is delivered to cell by carrier protein

Steroid hormone diffuses (through plasma membrane) into the target cells
Inside the cell hormone binds to an intracellular receptor-chaperonin complex
Chaperones detach from the receptor, leaving the hormone-receptor complex
Activated hormone-receptor complex moves through the nucleus to the chromatin and binds to
a DNA associated receptor (hormone response element)

Binding causes transcription of the gene to mRNA, for the production of specific protein
molecules
The mRNA directs protein synthesis

Control of Hormone Release:

(Most endocrine glands use a negative feedback system to synthesize and release their hormones.
Different stimuli cause neuronal or hormonal responses that activate endocrine gland activity)

Endocrine gland stimuli: (3 major types of stimuli trigger endocrine glands to release their
hormones):
1. Humoral Stimuli:
Secrete their hormones in direct response to changing blood levels of certain
critical ions and nutrients
Humoral: (various body fluids e.g. blood, bile, lymph, saliva)
Simples endocrine controls
o Glucose levels (insulin and glucagon)
o Ca++ levels (Parathyroid hormone PTH and calcitonin)
o Na++ in interstitial fluid (aldosterone and ANP)
2. Neural Stimuli:
Nerve impulses stimulating release of hormones
Ex. Sympathetic fiber stimulate adrenal medulla causing epinephrine and
norepinephrine to be released
Ex. Oxytocin and antidiuretic hormones are released by the posterior pituitary
gland, due to nerve impulses send by the hypothalamus
3. Hormonal Stimuli:
A hormone released from endocrine glands stimulating the release of other
hormones
Hypothalamus produces releasing or inhibiting hormones, which cause:
o Anterior pituitary gland to release its hormones into the bloodstream,
which in turn will activate some endocrine glands to produce and/or
secrete other hormones

Endocrine Organs of the Body

Pituitary Gland (hypophysis)

Lies in the sella turcica of the sphenoid bone and is attached to the hypothalamus by a stalk-like
structure called the infundibulum

Divided functionally and structurally:

Posterior pituitary gland:
o releases neurohormones (secreted by neurons) (posterior lobe +
infundibulum=neurohypophysis)
o composed of pituicytes (glia-like supporting cells) and nerve fibers
o storage area and not a true endocrine gland
Anterior Pituitary gland:
o Composed of glandular tissue
o Releases a number of hormones
o Anterior pituitary lobe + infundibulum= adenohypophysis
Blood Supply:
Anterior pituitary and infundibulum: via superior hypophyseal branches of internal
carotid artery
Posterior pituitary: via inferior hypophyseal artery

Pituitary-Hypothalamic Relationships

Posterior pituitary (neurohypophysis [posterior lobe])

Derives from down growth of hypothalamic tissue and maintains its neural connection
with the hypothalamus via nerve bundle called the hypothalamic-hypophyseal tract,
which runs through the infundibulum
Hypothalamic-hypophyseal tract arises from neurons in the supraoptic (ADH) and
paraventricular nuclei (OT) of hypothalamus
Their axon terminals are located in the posterior pituitary gland, and are supported by
pituacytes (glial cells)
Oxytocin made primarily by paraventricular neurons
Antidiuretic hormone (ADH) primarily by supraoptic neurons
Anterior Pituitary (Adenohypophysis *anterior lobe+was called the master gland
originates from superior out-pocketing of the oral mucosa (Rathkes pouch) and is
formed from epithelial tissue
After touching the posterior lobe (during embryonic development), anterior lobe loses
its connection with oral mucosa and adheres to the neurohypophysis, and becomes a
composite organ (combination of nervous and glandular tissue)
No direct neural connection with hypothalamus, but there is a vascular connection
Connect with hypothalamus via hypothalamic hypophyseal portal system
Note: Hypothalamus secretes regulating hormones (inhibiting or releasing) into the
hypophyseal portal system which circulate directly to adenohypophysis where they
activate cell of anterior pituitary to either secrete their hormone or to stop secretion
Anterior Pituitary Hormones:
All hormones except growth hormone affect their target cells via a cyclic AMP secondmessenger system
Pro-opiomelanocortin (POMC):

Its a pre-hormone, that is, a large precursor molecule that can be split
enzymatically into one or more active hormones, such as:
1. Adrenocorticotropic hormone-stimulates adrenal cortex
2. Melanocyte-stimulating hormone (MSH)- stimulates melanocytes in the
skin to produce melanin
In humans: it is a CNS neurotransmitter involved in control of
appetite
3. Opiates- (enkaphalin and beta-endorphin)
4. Lipotropins- (fat breakdown)
4 of the 6 anterior pituitary hormones are tropic, they regulate the function of
another endocrine gland:
o All anterior pituitary hormones except for growth hormone affect their target
cells via a cyclic AMP 2nd messenger system
o Tropic hormones
Thyroid stimulating hormone (TSH)-thyrotropic
Adrenocorticotropic hormone (ACTH)- adrenal cortex
Follicle stimulating hormone (FSH)-gonadotropic (testes/ovaries)
Luteinizing hormone (LH)- gonadotropic (testes/ovaries)
o Non-tropic hormones, effect non-endocrine targets
Prolactin (PRL)- milk production/lactation
Growth Hormone (GH)
o Pars intermedia
Melanocyte stimulating hormone (MSH)

Human Growth Hormone (hGH): (somatotropin)

o Produced by cells called somatotrophs (most numerous cells in anterior
pituitary) of the anterior lobe and has both growth promoting and metabolic
actions
o Growth hormone-releasing hormone (GHRH)-stimulates GH release
o Growth hormone-inhibiting hormone (GHIH) (Somatostatin)-inhibits GH
release
o Anabolic tissue building hormone, GH promotes protein synthesis, and
encourages the use of fats for fuel, thus conserving glucose
o Low levels of GH, glucose, IGF, fatty acids, increase amino acids and exercisein
blood will trigger the hypothalamus, via hypothalamic-hypophyseal portal
system to the anterior pituitary.
o Its targets are widespread (cartilage, bone, muscle, fat, and glucose)
o

Indirectly: Growth promoting effects are mediated indirectly by insulin-like

growth factors (IGFs)

Directly: Growth promoting effects mediated directly:

Growth promoting proteins produced by liver, skeletal muscle, bone

and other tissues
IGF stimulates actions required for growth:
1. Uptake of nutrients from the blood and their incorporation into
proteins and DNA, allowing growth by cell division
2. Formation of collagen and deposition of bone matrix

Exerts metabolic effects

Mobilizes fat from fat depots for transport to cells, increasing blood
levels of fatty acids
Decreases the rate of glucose uptake and metabolism
In the liver, it encourages glycogen breakdown and release of glucose to
the blood
Somatomammotropin:
Released by the placenta (resembles somatotropin in structure and
function
Increases maternal blood glucose and fatty acid levels -> nutrients
Functions to:
turn on virtually all body cells for growth
Increase rate of growth, development, and maintain size
Increase protein anabolism by an increase amino acid uptake by
cells
Increase catabolism of lipids and release of fatty acids from cells
(for energy)
It stimulates uptake of sulfur (chondroitin sulfate synthesis
[cartilage formation]
Increase glycogen synthesis (in the liver) -> preserving glucose
Increase glycogenolysis -> increases glucose in blood causing a
diabetogenic effect, because there is a decrease glucose
catabolism (which leave glucose in the blood)
Abnormalities:
Hypersecretion of hGH
Giantism:
seen in children, before the epiphyseal plate is closed,
this will cause extreme elongation of long bone ( up to 8
ft. tall),
m/c: due to tumor
acromegaly:
seen in adults, after epiphyseal plate has closed
enlarged and thickened bones (hands, feet, face,
cranium, supraorbital ridge, nose, and lower jaw)

soft tissue can continue to grow-> tongue, liver and

kidenys
chronic hyperglycemia results in diabetes mellitus and
atherosclerosis
Hyposecretion of hGH:
Pituitary dwarfism: In children
Delayed growth of long bones; early closure of
epiphyseal plates
Body organs fail to develop and grow
Mild obesity
Retarded development of adult reproductive function;
child-like features
Progeria: In children
Apparent genetic trait; could look very old by the time
theyre 7 years old
Causes degenerative changes to occur shortly after the
first year of life

Thyroid Stimulating hormone (TSH): (thyrotropin)

tropic hormone that stimulates normal development and secretory activity of the thyroid gland
Released from anterior pituitary cells called thyrotrophs- trigged by hypothalamic peptide
thyrotropin-releasing hormone (TRH) from hypothalamus (low levels of T3 and T4, glucose,
pregnancy (in infants) cold in blood will trigger the hypothalamus ) via hypothalamichypophyseal portal system to the anterior pituitary
TSH target, the thyroid gland -> stimulates synthesis and secretion of thyroid hormones (TH),
thyroxin T4 and triiodothyronine T3
Regulated by negative feedback system:
High levels of T3 and T4, glucose in blood will trigger the hypothalamus to release
somatostatin (GHIH) (there is NO thyroid inhibiting hormone) to stop anterior pituitary
secretion of thyroid stimulating hormone (TSH)

Adrenocorticotropic Hormone (ACTH): (CORTICOTROPIN)

Secreted by the corticotrophs of the anterior pituitary

ACTH stimulates the adrenal cortex to release corticosteroid hormones, most importantly
glucocorticoids that help the body resist stressors
Elicited by hypothalamic corticotropin-releasing hormone (CRH)
peaks in the morning, shortly before awakening
CRH released due to fever, hypoglycemia and stressors of all types

Regulated by a negative feedback system:

High levels of cortisol (glucocorticoids), glucose and normal daily cycles (higher levels
of ACTH) will trigger the hypothalamus to release corticotropin inhibiting hormone
(CIH)

Gonadotropins: FSH and LH (both)

Regulate the function of the gonads (ovaries and testes)

Follicle stimulating hormone (FSH)
In both sexes, FSH stimulates gamete (sperm and egg production)
Released from gonadotrophic cells of anterior pituitary, in response to gonadotropin
releasing hormone (GnRH) from hypothalamus
o In females: decreased levels of estrogen, progesterone and inhibin will trigger
the hypothalamus to release GnRH
o In Males: decreased levels of testosterone and inhibin will trigger the
hypothalamus to release GnRH
o Via hypothalamic-hypophyseal portal system to the anterior pituitary
Negative Feedback system:
o Incr. levels of estrogen, progesterone and inhibin will trigger release of
gonadotropin inhibiting hormone (GnIH)
o Incr. levels of testosterone, and inhibin will trigger release of GnIH
Abnormalities: dec. levels will cause limited sexual maturity, for both FSH and LH
Luteinizing hormone (LH):
Promotes production of gonadal hormones
In females: works with FSH to cause an egg-containing ovarian follicle to mature
Independently triggers ovulation and promotes synthesis and release of ovarian
hormones (estrogen and progesterone)
In Males: LH stimulates interstitial cells of the testes to produce the male hormone
testosterone
o Only in Males: LH is called interstitial cell stimulating hormone (ICSH)
Prolactin (PRL):
Prolactin targets the: alveolar cells (breast epithelial cells) of breasts: triggers milk
production
Produced by lactrotrophs (cells) in response to prolactin releasing hormone (PRH) from
hypothalamus
(Incr. estrogen in blood and breastfeeding will trigger the hypothalamus), via
hypothalamic-hypophyseal portal system to the anterior pituitary
PRL release is primarily controlled by an inhibitory hormone: prolactin-inhibiting
hormone (PIH), now known to be dopamine, which prevents prolactin secretion
Regulated by negative feedback system:
o Decreased blood estrogen will trigger release of PIH aka dopamine
o Incr. estrogen -> Incr. PRH/Decr. PIH (hypothalamus) -> Incr. PRL (ant. Pituitary)

Decr. estrogen ->Incr. PIH/Decr. PRH (hypothalamus) -> Decr. PRL (ant.
Pituitary)
Abnormalities:
o Hyperprolactinemia: More common than hypoprolactinemia
Females:
Incr. due most commonly to Prolactinoma (tumors), but can
occur with an increase of thyroid releasing hormone (TRH)->
increase prolactin and TSH
Can lead to:
Galactorrhea (excess milk secretion)
Oligomenorrhea, amenorrhea, anovulation, and
infertility

Males:
Could see increase in headaches, sexual dysfunction, visual
problems, decreased testosterone and impotence
Gynomastia (breast development), galactoria (lactation) or
both

Posterior Pituitary and Hypothalamic Hormones:

Oxytocin (OT):
Produced by paraventricular nucleus of the hypothalamus and transported via
hypothalamic-hypophyseal tract (neural stimuli) to be stored in, and released by
posterior pituitary axon terminals
Regulated and released higher in late pregnancy and in nursing women by Positive
feedback system:
o In myometrial cells (muscles of uterus): Stretching of the uterus and cervix as
birth nears dispatches afferent impulses to paraventricular nucleus
(hypothalamus) to stimulate release of OT, allowing stronger contractions
o In myoepithelial cells (milk release) of the breasts: suckling of breasts (specific
pressure receptors in nipple areolar complex) will send impulses to
paraventricular nucleus to stimulate release OT
Antidiuretic Hormone (ADH):
Diuresis: is urine production
ADH: inhibits or prevents urine formation; prevents wide swings in water balance;
helping the body avoid dehydration and water overload
Osmoreceptors: continually monitor the solute concentration of and thus the water
concentration of the blood

when solute become too concentrated (inadequate fluid intake), osmoreceptors

transmit excitatory impulses to the hypothalamic neurons, which synthesize and
release ADH
o decr. Blood volume, decr. BP
Produced by supraoptic nucleus of the hypothalamus and transported via the
hypothalamic-hypophyseal tract (neural stimuli) to be stored in, and released by
posterior pituitary axon terminals
ADH target are:
o Kidney tubules and collecting ducts (via cAMP) to increase reabsorption of
water
o Prevents excessive urine production by removing water from urine and
returning it to the bloodstream
Using a negative feedback mechanism:
Decr. Solute concentration (decr. Osmolality), increase blood
volume, increase blood pressure, will inhibit the hypothalamus
(decr. Impulses)
Abnormalities:
o Diabetes insipudus:
Hyposecretion of ADH-> causes ongoing excretion of large amounts of
H20 in the urine (from 1-2 L/day up to 12L/day) and also causes
increased thirst
Due to dysfunction or trauma to supraoptic nuceli of the hypothalamus
or posterior pituitary
ADH Hypersecretion -> increased fluid retention -> (relative)
hyponatremia (decr. Blood Na+)

Thyroid Gland:
1. Location and structure:
Located in the anterior neck, on the trachea just inferior to the larynx
Has right and left lateral lobes connected by a mass tissue called isthumus just below cricoid
cartilage
Largest pure endocrine gland in the body
Has a very rich blood supply: superior and inferior thyroid arteries, which branches of common
carotid arteries bilaterally
Histologically:
Internally, composed of follicles (hollow, spherical)
Walls of each follicle are formed by (cuboidal or squamous) epithelial cells called follicle
cells-> produce glycoprotein thyroglobulin

 the lumen or central cavity of follicles stores colloid, an amber-colored, sticky material
consisting of thyroglobulin molecules with attached iodine atoms
Parafollicular cells:
o produce calcitonin (thyrocalcitonin-decrease blood Ca+)
o cells that dont reach the lumen, lie in the soft CT that separates and surrounds
the thyroid follicles
Thyroid hormone is derived from this iodinated thyroglobulin
2. Thyroid Hormones (iodinated thyroglobulin)
Composed of two iodine-containing amine hormones:
1. Thyroxine (T4)
Major hormone secreted by thyroid follicles but many molecules are converted into T3
(by enzyme deiodinase)
4 iodine atoms (90%)
Secreted in greater quantities (but most is converted to T3)
2. Triiodothyronine (T3)
Formed by conversion of T4 to T3
3 iodine atoms (10%)
Much more potent and 10x more active than T4 (bind more readily to receptors)
Thyroid hormone increases the rate of metabolism (approx. 60 to 100% above normal) in the
body, in most (not all) of the bodys cells, except brain, spleen, testes, uterus, lungs, and retina
3 principle effects:
Regulation of metabolism (anabolism and catabolism):
o Metabolism-> cellular activity:
Anabolism: building, binding (small structures into larger structures)
Catabolism: breaking down structures
o Inc. Protein synthesis (spares amino acids)
o Stimulates almost all aspects of carbohydrates and lipid catabolism in almost
every cell of the body
o Overall it increases rate of catabolism of glucose and oxygen consumption
(oxidation) increase ATP production-> Incr. basal metabolic rate -> Inc. body
heat production (calorigenic effect)
Regulation of growth and development:
o Especially in children works with hGH and insulin to produce body growth
(skeletal and nervous system)
o Inc. overall (structures and functions) maturation and reproductive capabilities
Maintains normal nervous system functioning:
o Extremely significant in fetal and newborn nervous system development
o Ill effects of hypothyroidism during fetal development:
Fewer overall neurons ] Mental retardation
Defective myelination of neurons ] Mental retardation
All of the above can be seen in varying degrees

Ill effects of hypothyroidism during childhood development

Small stature
Decrease development of many structures including organs

Synthesis:
Thyroglobulin is synthesized and discharged into the follicle lumen
o Synthesized on the ribosomes of the thyroids follicle cells
o Thyroglobulin is transported to the Golgi apparatus where it is packed into
transport vesicles
o Vesicles move to the apex of the follicle cell and discharge their contents into
the lumen to be stored as colloid
Iodide is trapped
o Follicle cells must accumulate iodides (anions of iodine, I-) from the blood
o Once trapped, iodide moves into the lumen by facilitated diffusion
Iodide is oxidized to iodine
o At the border of the follicle cell and colloid, iodides are oxidized (by removal of
electrons) and converted to iodine (I2)
Iodine is attached to tyrosine
o Iodine is attached to tyrosine amino acids that form part of thyroglobulin colloid
o This iodination occurs at the junction of the follicle cell apex and colloid and is
mediated by peroxidase enzymes
o Attachment of one iodine to tyrosine produces monoiodotyrosine (MIT or T1)
o And two attachments produce diiodotyrosine (DIT or T2)
Iodinated tyrosines are linked together to form T3 and T4
o Enzymes in the colloid link MIT and DIT together
o Two linked DITs result in T4
o DIT and MIT result in T3
o Still part of thyroglobulin colloid
Thyroglobulin colloid is endocytosed
o In order to secrete hormones, follicle cells must reclaim iodinated thyroglobulin
by endocytosis and combine the vesicles with lysosomes
Lysosomal enzymes cleave T4 and T3 from thyroglobulin and the hormones diffuse
from the follicle cell into the bloodstream
o Main hormonal product is T4
o Some T4 is converted to T3 before secretion, but most T3 is generated in the
peripheral tissue
Transport and Regulation:
Thyroxine-binding globulins (TBGs):
o produced by the liver
o Most T4 and T3 released, immediately bind to this transport protein in the
bloodstream and be transported as protein-bound iodine (PBI)
T3 can/will effect cells by either:
1. Bind to surface receptor (2nd messenger system)

2. Diffuse into cell and bind to nuclear receptor

3. Exception: bind to mitochondria causing increase oxygen uptake -> increase ATP
production
o How it effects the cell depends on the receptor type and target cell
Negative feedback system:
o Decrease TH -> increase thyroid-stimulating hormone (TSH and ultimately
TH
o Rising TH->inhibit TSH
o Factors that inhibit TSH release include GHIH, dopamine, glucocorticoids
and high blood iodide concentration
Metabolic Disturbances:
Hypothyroid disorders:
o Myxedema:
severe or prolonged adult hypothyroidism
S/S:
Face will swell and look puffy, dry skin
Low metabolic rate, low HR (enlarged heart), low body temp.
(sensitive to cold)
Constipation
Edema, lethargy, mental sluggishness (not mental retardation)
o Endemic or colloidal goiter:
Due to lack of iodine
Follicle cells produce colloid but cannot iodinate it and make functional
hormones
Follicle cells enlarge as a result of increasing amounts of hormone
release and unusable colloid (Inc. colloid no production of functional
hormone)
Eventually the gland will atrophy
Goiter is caused by thyroid gland overworking
Cretinism: severe hypothyroidism in infant
S/S:
(child may look normal at first because mom has
provided the hormones)
Mentally retarded because brain will not develop fully
Short, disproportionately sized body and a thick tongue
and neck
Not reversible
Tx: administer thyroid hormone replacement
Hyperthyroid disorder:
o Graves disease:
Most common pathological autoimmune disease

Abnormal antibodies produces which are directed against thyroid

follicle cells
Antibodies paradoxically mimic TSH and continuously stimulate TH
release
S/S: Inc. metabolic rate, sweating, rapid, irregular HR, nervousness,
weight loss
Exophthalmos: protrusion of the eyeballs may occur if the tissue behind
the eye becomes edematous and then fibrous
Tx: removal of thyroid gland or ingestion of radioactive iodine (destroys
most active thyroid cells

Thyrocalcitonin (CT):
Polypeptide hormone produced by the parafollicular, or C, cells of the thyroid gland
Function:
o Lower blood Ca2+ levels in the blood
Targets:
o Skeleton/Bone:
Inhibits osteoclast activity/ Stimulates osteoblast activity
Inhibiting bone resorption and release of Ca2+ from bone matrix
Stimulates Ca2+ uptake and incorporation into bone matrix
o Kidneys:
Decrease resorption of Ca++ by kidney tubules
o Small Intestines:
Decrease Ca++ absorption by small intestine tract
It uses a negative feedback system
Humoral control: it has a direct effect on the C cells of the
thyroid gland (it bypasses pituitary gland)
Decrease blood calcium levels cause calcitonin secretion to stop
Parathyroid Gland
Found on posterior surface of thyroid gland lobes (usually exists 4 glands)
Histologically: 2 types of epithelial cells
1. Oxyphil cells: function not known
2. Chief cells: secrete parathyroid hormone
PTH functions to increase levels of calcium in blood
o 3 targets:
1. Bone/Skeletal
by decreasing deposition of Ca++ onto bone it will cause an increase
of Ca++ and phosphate release into the blood (increase osteoclastic
and decrease osteoblastic activity)
2. Kidneys:

Decrease Ca++ excretion by kidneys tubules/ increase Ca++

absorption (into blood) and complete activation of vitamin D to
calcitriol/Vita D3 (calcitrol=vitamin D3-active form of vitamin D
3. Small intestine:
Promotes activation of vitamin D, thereby
Increasing calcium absorption from the small intestines (in the
presence of vita D3)
o Negative feedback system:
Humoral control: it has a direct effect on the C cells of the thyroid
gland (it bypasses pituitary gland)
Decrease blood calcium levels causes calcitonin secretion to stop
o Antagonist to calcitonin (CT)
o Uses a negative feedback system:
Humoral control: it has a direct effect on the parathyroid gland
Increase calcium levels causes PTH secretion to stop (bypasses pituitary
gland)
Abnormalities:
o Hypoparathyroidism:
Decreased calcium in blood
S/S:
Decrease in osteoclastic activity
Spontaneous depolarization of neurons & muscle fibers (twitch,
spasm, tetany)
TX:
Not parathyroid replacement (lasts only a few hours. Way too
expensive)
Use approx. 100,000 units of Vita D/day and 1-2 grams of
Calcium/day
o Hyperparathyroidism
Calcium is leached from the bones, and bones soften and deform
(increased calcium in blood)
PTH deficienty
S/S:
Most commonly due to a tumor
Seen in females more than males
Decalcification of bones
Muscular weakness
Abdominal pain and constipation
Decreased relaxation of heart during diastole

Adrenal Glands

The body has two adrenal (suprarenal) glands, one on top of each kidney
Each one is both structurally and functionally different
Adrenal Cortex: (3 zones)
o Derived from mesoderm embryonically (80% gland)
o From same region that gives rise to the gonads
o Encapsulating the medulla and form the bulk of the gland
o Surrounded by CT capsule
Adrenal medulla:
o Derived from ectoderm neurocrest cells (20% gland)
o Same as postganglionic sympathetic fibers (ANS, sympathetic)
Adrenal Cortex:
Subdivided into 3 zones -> secrete corticosteroids (cholesterol based)
Outer zone: Zona glomerulosa (approx. 15% cortex)
o Lies directly beneath the capsule
o Cells arranged in loops made up of round balls (glomeruli)
o Produce mineralocorticoids (mostly aldosterone), hormones that help control
the balance of minerals and water in the blood
Middle zone: zona fasciculate
o Widest of the three
o Cells arrange in linear cords (fascicles)
o Produce mostly glucocoritcoids->cortisol ([hydrocortisone]), most significant in
humans), to increase blood glucose levels
Inner zone: zona reticularis
o arranged in cords of cells that branch freely (net-like)
o Produce small amounts of adrenal sex hormones, or gonadocorticoids, mostly
male hormone androgens: dehydroepiandrosterone DHEA (which body cells
convert to (testosterone) at the tissues and glucocorticoids
Middle and Inner Zone share production of gluco and gonado-corticoids, although each
layer predominately produces one type
Mineral corticoids:
Aldosterone (most potent mineralocorticoid) is secreted from zona glomerulosa; most
potent (95% of all hormones produced)
Function is to regulate the electrolyte (mineral salt) concentrations in extracellular
fluids, particularly of NA+ and K+
Na+ is the single most abundant cation in extracellular fluid, and the amount of Na+ in
the body largely determines the volume of extracellular fluid
K+ sets the resting membrane potential of all cells and determines how easily action
potentials are generated in nerve and muscle
Aldosterone
1. reduces excretion of Na+ from the body

2. primary target: kidney tubules, where it stimulates Na+ reabsorption and water
retention accompanied by elimination of K+
Aldosterone:
Target: Kidneys (afferent arterioles going into the glomerulus (GFR)
Effects: Incr. vasoconstriction-> Decr. Filtration -> decr. Urine production -> Inc. BV->
Inc. BP
Target: Hypothalamus (posterior pituitary)
Effect: Incr. Antidiuretic hormone secretion -> decr. Urine production -> Inc. BV -> Inc.
BP
Target: Kidneys
Effect: 1) Inc. Na+ reabsorption by collecting ducts (Dec. Na+ into the urine out of the
blood/body, so it stays in the blood) -> Inc. BV-> Inc. BP
2) Inc. Renin (a small protein enzyme released as a result of low blood pressure)> Inc. BV -> Inc. BP
pH balance:
Inc. sodium into blood-> will Inc. number of H+ ions leaving blood and entering
urine; this helps Incr. blood pH
With Incr. sodium (positive ions) in the blood -> Incr. positive charge in the BV, this
will draw negative ions out of urine into blood (Cl or HCO3)

4 mechanisms regulate aldosterone secretion:

1. The renin-angiotensin mechanism:
Influences both BV and BP by regulating the release of aldosterone and therefore Na+
and water reabsorption by kidneys
Specialized cells of juxtaglomerular apparatus in kidneys respond when BP (or BV)
decline. These cells secrete renin into the blood, which claves off part of plasma protein
angiotensinogen triggering enzymatic cascade leading to formation of angiotensin II,
a potent stimulator of aldosterone release by the glomerulosa cells
Target: Adrenal cortex
Effect: Incr. aldosterone release-> (reabsorbs Na+ at kidneys)-> Incr. BV-> Incr. BP
Angiotensinogen (liver plasma protein)
Renin (enzyme from kidneys)
Angiotensin I (10 amino acids)
Angiotensin converting enzyme (ACE) (happens in the lungs)
Angiotensin II (8 amino acids)
2. Plasma concentrations of potassium
Levels of K+ in blood directly influence zona glomerulosa cells in the adrenal cortex to
release aldosterone.
Incr. Ka+ = Aldosterone release/ Dec. K+ = aldosterone inhibit

 Decr. Na+ = Aldosterone release/ Incr. Na+ = aldosterone inhibit

3. adrenocorticotropic hormone (ACTH):
released by anterior pituitary, it has a minor effect on aldosterone secretions
with excessive stress hypothalamus secretes corticotrophin-releasing hormone (CRH) ->
Incr. ACTH -> Incr. Aldosterone secretion
This ensures adequate delivery of nutrients and respiratory gases due to increased BV
and BP during stressful period
4. Atrial natriuretic peptide (ANP):
Hormones secreted by the heart when BP rises
Fine tunes BP and sodium-water balance of the body
Inhibits renin-angiotensin mechanism
o Blocks renin and aldosterone secretion and inhibits other angiotensin-induced
mechanism that enhance water and Na+ reabsorption
Overall influence is to decrease BP by allowing Na+ (and water) to flow out of the body
in urine
Structural abnormalities:

Hyperaldosteronism:
S/S:
o Decreased K+ -> hypopolarization-> alteration of electrical excitability of
neurons and muscle cells causing -> muscle weakness develops

Hypoaldosteronism:
S/S:
o Decreased Na+ and H2O reabsorption-> decreased BV-> BP
o Increased K+ (by 60 to 100%) -> serious heart toxicity, weakness of heart
contraction, and the development of arrhythmia-> can lead to heart failure

Addisons Disease:
Lack of all categories of specific hormones from adrenal cortex. Usually due to the
destruction of entire adrenal cortex. Majority of cases are caused by autoimmune
destruction
Effects:
o Lack of Aldosterone:
Inability to reabsorb Na+ and water from kidneys; not enough water is
reabsorbed via ADH and a low blood volume causes hypotension,
particularly with changes in pressure
Hyperkalemia (high K+ blood levels)
Renin-Angiotensin II mechanism is activated-> Incr. rennin (in response
to low glomerular filtration rate-GFR
Any condition that results in low GFR will activate rennin cascade

Lack of Androgens (Testosterone)

Female: decrease in body hair, especially in pubic and axillary regions,
and hair on extremities
Male: No effect due to high level of testosterone production by testes
o Lack of cortisol:
Inability to mobilize amino acids
Decrease in gluconeogenesis
An overall inability to resit any type of biological stress such as infection
No cortisol in blood to feedback hypothalamus, hypothalamus
continues to direct anterior pituitary to release ACTH to stimulate
adrenal cortex. An over-production of ACTH mimic MSH due to similar
amino acid sequencing, especially on sunlight exposed skin
Glucocorticoids:
Zona fasciculate: Hormones include: cortisol (hydrocortisone), cortisone, and
corticosterone
o Only cortisol is secreted in significant amounts in humans
Glucocorticoid secretion is regulated by negative feedback
o Cortisol release is prompted by ACTH (anterior pituitary), triggered in turn by
hypothalamic releasing hormone CRH
o Rising cortisol levels feed back to act on both hypothalamus and anterior
pituitary, preventing CRH release and shutting off ACTH and cortisol secretion
Influences the energy metabolism of most body cells and helps us to resist stressors
o Helps body adapt to intermittent food intake by keeping blood glucose levels
constant
o Maintain BP by increasing the action of vasoconstrictors
o Severe stress due to hemorrhage evokes a dramatically higher output of
glucocoritcoids
o Cortisol secretions are diurnal related to sleep/wake
o Cortisol -> incr. glucose, fats and proteins in blood
o Also activated by sympathetic during physical or mental stress
o Influences metabolism of most cells in body, helps adapt to internal and
external changes by maintaining blood sugar levels
o Tissue repair
o Inhibits immune system
Prime metabolic effect is to provoke gluconeogenesis (formation of glucose from fats
and proteins and NOT carbohydrates)
o Protein:
Catabolism (muscle breakdown)->mobilization of amino acids-> for
gluconeogenesis (resynthesizing glucose) and other molecules
Stored proteins are broken down to provide building blocks for repair or
formation of enzymes to be used in metabolic processes
o Fats:

Lipolysis to fatty acids (for energy) or to ketones, mobilization fats-> for

gluconeogenesis (resynthesizing glucose)
Mobilizes fatty acids from adipose and encourages their increased use
for energy
o Carbohydrates:
At the liver, causes glycolysis which will increase blood glucose
Increase cortisol released during stress (fright, overwork, trauma, infection, surgery,
etc)
o The hypothalamus will detect and start cycle for its release
Cortisol will decrease inflammatory effects, by inhibiting histamine release
from mast cells (inflammatory substances), because of decreased capillary
permeability (decreased vessel content into interstitium)
Cortisol excess is associated with significant anti-inflammatory and antiimmune effects
o Depress the Immune System
Inhibit lymphocyte production, especially T lymphocytes
Macrophage cell membranes stabilize (they dont rupture as easily)
lysosome in macrophage cant be released -> depress phagocytosis
Decrease chemotaxis (a way by which phagocytes find their way to the
injured site) to injured sites
Decrease fever by a decreasing release of interleukin-1 from WBC
(stimulate hypothalamus temp. control mechanism) -> decrease body
temp. -> decrease vasodilation -> decrease blood to injured areas
o Decrease osteoblastic activity
Depress cartilage and bone formation
o Promotes changes in cardiovascular, neural, and gastrointestinal function
o When used as a Tx: after transplant surgery, decrease immune system and
chances of rejection
o Enhances sympathetic nervous systems vasoconstrictive effects, and the rise in
BP ensures that nutrients are quickly distributed to the cells
Abnormalities:
o Excess: Cushings disease
o Deficiency: Addisons disease

Gonadocorticoids (sex hormones):

Weak androgens (male sex hormones) such as androstenedione and
dehydroepiandrosterone (DHEA) and some female hormones (estradiol and other
estrogens)
Converted to testosterone in tissue cells, or estrange (female sex
hormones) in females
Increase sex drive and cause development of secondary sex characteristics
o In females:

 It may provide some estrogen during menopause

Is believe to contribute to libido and other sexual behaviors
Abnormalities:
o Androgenital syndrome (virilism or masculinization)
More noticeable in females and in prepubescent boys;
They will develop many masculine adult characteristics, e.g.., deeper
voice, beard, change in escusion pattern, etc..
In prebuscent males-> early development of secondary sex
characteristic and sexual drive
Difficult to detect in adult males because of the foregone development
and ongoing testosterone release by gonads

Adrenal Medulla:

Chromaffin cell
Develops from neurocrest tissue which is the same source as the postganglionic cell of
sympathetic nervous system
Crowd around blood-filled capillaries and sinusoids
Directly stimulated by preganglionic fibers of ANS, this allows for a more rapid response
to stimuli
Synthesize catecholamines-epinephrine and norepinephrine via molecular sequence
from tyrosine to dopamine to NE to epinephrine
Hormones:
Catecholamines: epinephrine (adrenaline 80%) and norepinephrine (noradrenaline
20%)
These hormones are referred to as sympathomimetic amines
Intensifies the action already produced by sympathetic
Action:
o Increase BP due to increased heart rate and force of contraction
o Increase respiration and increase in blood sugar levels-> increase in metabolic
rate
o Decrease digestion
o Norepinephrine also helps with these effects, but has a bigger influence on
peripheral vasoconstriction
Abnormality:
Pheochromocytoma: (chromaffin cell tumor)
o Causes Hypersecretion of catecholamines and produces a massive out of
control sympathetic response
o Hyperglycemia, Increased metabolic rate, heart rate, hypertension, seating

Pancreas:

A slightly flattened organ, located behind the stomach between the spleen and duodenum. In
adults it consists of a head, body, and a tail
Classified as a mixed gland-> both endocrine and exocrine gland

Exocrine:
o produces digestive enzymes via acinar cells, that is carried by ducts to the small
intestine during digestion
Endocrine:
o Scattered among acinar cells are pancreatic islets, or Islets of Langerhans:
(approx. 2 million), tiny cell clusters that produce pancreatic hormones
Islets contain two major populations of hormone-producing cells:
1. Alpha (a) cells: glucagon-synthesizing
Hyperglycemic hormone
2. Beta (b) cells: more numerous insulin-producing
Hypoglycemic hormone
o contains at least 3 functionally different cell types:
1. alpha cells secrete glucagon
2. beta cells secrete insulin
3. delta cells secrete somatostatin (growth hormone inhibiting hormone
[GHIH])
Glucagon (20%) and insulin (75%), both hormones are concerned with metabolism and
regulation of blood sugar levels
o Glucagon is very potent (alpha cell)
Fxn: increase secretion of glucagon with a decrease of blood glucose,
and vice versa
Inhibited by increase blood sugar levels and somatostatin
A hyperglycemic hormone whose principal physiological activity is to
cause an increase in blood glucose levels
Major Target: Liver
1. Glycogenolysis: breakdown of glycogen to glucose
2. Gluconeogenesis: synthesis of glucose from lactic acid and from
noncarbohydrate molecules
3. Release of glucose to the blood by liver cells, causing blood glucose
levels to rise
4. Promotion of lipolysis-> (increase triglyceride breakdown to fatty
acid) as an energy source

5. Increase amino aci uptake by the liver for gluconeogenesis

Abnormalities:
o Glucagonomas (glucagon secreting tumor)-> hyperglycemia (increase blood
glucose) -> may develop diabetes mellitus
o Necrolytic migrator erythema: strange skin rash, mostly in anogenital region
Insulin:
o More potent and longer lasting than glucagon (beta cells)
o Increase secretion of insulin with an increase of blood glucose and vice versa,
also inhibited by somatostatin
o Synthesized as part of as part of a larger polypeptide chain called proinsulin
o A hypoglycemic hormone whose principle physiological activity is to cause a
decrease in blood glucose levels, by accelerating transport of glucose into cells
o Circulating insulin lowers blood glucose levels in three main ways:
Insulin enhances membrane transport of glucose (and other simple
sugars) into body cells, especially muscle and fat cells. (It does not
accelerate glucose entry into liver, kidney, and brain tissue, all of which
have easy access to blood glucose regardless of insulin levels
Insulin inhibits breakdown of glycogen to glucose
Inhibits the conversion of amino acids or fats to glucose
o Major targets: the liver and muscles:
Increase movement of glucose into cells for storage as glycogen
Glycogenesis-> the conversion of glucose into glycogen (stored from
glucose), phosphorylation
Increase glycogenesis-> (glucose into glycogen)
Decrease glycogenolysis (hydrolyses of glycogen to glucose), and
gluconeogenesis (production of glucose from non-carbohydrate sources
[proteins, amino acids, fatty acid, glycerol, lactic acid])
Increase lipogenesis (formation of fat from glucose and other nutrients)
and (decrease lipolysis (breakdown of fats)-> decrease triglyceride
breakdown to fatty acids)
Synthesis of fatty acids (liver), then transported by VLDL to fat cells
where they are stored as triglycerides
Increase amino acid uptake by cells; stimulates protein synthesis
Does not have effect on brain and kidneys
Stimulated by Vagal nerve, swallowing reflex and gastrointestinal
hormones (gastrin, secretin, cholecystokinin, CCK)
Abnormalities:
o Hypoglycemia: (low blood sugar levels)
o S/S: nervousness, dizziness, loss of consciousness
o Diabetes mellitus:

Hyperglycemia, an elevation of glucose in the blood (secretion of little

or no insulin, or decrease in insulin r/c)
Metabolic acidosis-when glucose cant be used-> increase fatty acid and
keto acids will lower pH (ketones formed when fats (lipids) are broken
down)
Hyperlipidemia (increase lipids in blood) using fats for energy->
atherosclerosis (fat deposits on blood vessel walls)
Dehydration, inability to reabsorb H20, and polyuria (increase urine
production), with associated polydipsia (increase thirst)
Muscle atrophy, protein breakdown for energy
Coma, which may lead to death

Gonads:

Produce steroid sex hormones which triggers target cells and maintain bodily functions, identical
to those produced by adrenal cortical cells
Release of gonadal hormones is regulated by gonadotropins
Ovaries:
Small, oval organs located in the females abdominopelvic cavity
Produce ova (eggs), estrogens, progesterone and other hormones
Estrogen:
o Responsible for maturation of the reproductive organs
o And appearance of the secondary sex characteristics of females at puberty
o Along with progesterone, estrogens promote breast development and cyclic
changes in the uterine mucosa (menstrual cycle)
o Ongoing production of oocytes (eggs) and the maintenance of the reproductive
organ in females
Testes:
Located in an extra-abdominal skin pouch called the scrotum
Produce sperm and male sex hormones, primarily testosterone
During puberty, testosterone initiates maturation of male reproductive organs and
appearance of secondary sex characteristics and sex drive
Necessary for ongoing production of sperm and maintenance of the reproductive organ
in males

Pineal Gland:

Tiny, pine cone-shaped; hangs from the roof of the third ventricle in the diencephalon

Consists of neuroglial cells and pinealocytes

Lying between pinealocytes in adults are dense particles containing calcium salts
Largest in a child and involutes in adult
Secretions peak between the ages of 1 and 5 yrs., and decrease by 75% by the end of puberty
Melatonin:
Major secretory product
Powerful antioxidant and amine hormone derived from serotonin
Concentrations in blood rise and fall throughout the day
Peak levels occur during the night and make us drowsy, and lowest levels occur around
noon
Inhibits reproductive activities by inhibiting gonadotropic hormone release
Inhibits early sexual maturation (onset of puberty)

Thymus:

Bilobed, deep to sternum, on anterior bilateral aspects of the trachea

Composed mostly of hormone producing cells and very large in infants/children
Mostly fat and fibrous CT in infants/children
Thymopoietin, thymosin (thymic humoral factor [THF], and thymic factor [TF]):
Immunocompetency for development and activity of T lymphocytes
Essential for normal development of a childs immune system