Hormone

Hormonal cascade system

 Quantity
o HypoT release hormone (ng), trigger the ant pit to release hormone (𝜇g), trophic
hormone stimulate the target gland to release hormone (mg)
o Small amount of releasing hormone trigger release of large amount of other hormone
 Life span
o Life span of releasing hormone is short while the target hormone life span is longer
 Determination of ant pit activity
o LH and FSH is injected to the patient, if gonad does not secrete the hormone →
dysfunction of gonad
o If gonad secrete hormone, test of ant pit by given intravenous GnRH
o If ant pit does not secrete LH and FSH → defects of ant pit

Mechanism of steroid hormone

 Steroid hormone is permeable to the membrane, enter the cell without receptor
 Heat shock binding protein;
o at resting state, protein is bind to the active site of the receptor
o ↑ ℃, the protein dissociate from receptor, active site of the receptor exposed
o Hormone bind to the receptor
 Hormone bind to the receptor forming the hormone-receptor complex
 Receptor act as transporter and transport the hormone to the nucleus
 This complex interact with hormone receptor element, HRE exist in DNA– alter the gene
expression
 ↑ gene expression, HRE called as enhancer
 Inhibit gene expression, HRE called as silencer
 Eclampsia in pregnant woman
o Aldosterone receptor has lower affinity to progesterone
o But when mutation on steroid receptor, affinity to progesterone ↑

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 o In pregnancy, progesterone ↑, binds to aldosterone receptor, H2O retention,
hypertension, eclampsia occur

Congenital adrenal hyperplasia

 Deficiency 21-hydroxylase which is involve in synthesis of cortisol and aldosterone
 ↓ cortisol and aldosterone
 ↑ ACTH secretion, as a result, ↑ DHEA, ↑androstedione, ↑testosterone production
 Testosterone cause male characteristic, hirsutism

Cushing syndrome

 Aldosterone, cortisol, adrenal endrogen

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  Possible cause
o Pituitary tumour, ↑ACTH secretion, ↑ synthesis of steroid hormone at adrenal gland,
↑cortisol, aldosterone, adrenal endrogen
o Ectopic ACTH, ↑ACTH level, ↑ synthesis of steroid hormone at adrenal gland,
↑cortisol, aldosterone, adrenal endrogen
o Normal level of ACTH, adrenal tumor, ↑ synthesis of steroid hormone at adrenal gland,
↑cortisol, aldosterone, adrenal endrogen
o Iatrogenic, ↑cortisol, aldosterone, adrenal endrogen
 Thinning of skin; breakdown of connective tissue collagen by excessive cortisol, fat and protein
mobilize from periphery to the liver
 Hypertension; aldosterone action, cortisol bind to the aldosterone receptor, give the
aldosterone effect, Na+ retention, H2O retention, ↑plasma volume, ↑blood pressure

Inactivation & excretion of steroid hormone

 Reduction in the liver
 Exception to testosterone reduction → dihydrotestosterone, for external sex characteristic
development
 Conjugate with diglucuronide and/or sulphate to be excreted in the urine
 Become hydrophilic and solubilize

Genes and biosynthesis of polypeptide hormone

 Maturation through proteolytic enzyme; insulin
o Synthesized as preproinsulin
o In ER, proteolytic enzyme release sinal peptide from proinsulin
o In the GA, peptide C is release and active insulin with2 peptide chain and 3 disulphide
bridges formed
 Gene code for multiple copies of enzyme; enkephalin, POMC

Inactivation and degradation of polypeptide hormone

 Hydrolysis of lysosomes
 Action of specific enzyme; insulinase act on insulin
 Cleaves of cyclic glutamate ring/ C – terminal amide
o Enzyme in blood able to cleave
 TRH cyclic glutamate ring/ C – terminal amide
 GnRH cyclic glutamate ring/ C – terminal amide
 CRH C – terminal amide
o ↓ life span of releasing hormone
 Action of cystine aminopeptidase & glutathione transhydrogenase

G protein (know 1 or 2 subunit 𝛼)

 Composed of 𝛼, 𝛽, 𝛾 subunit
 𝛼 subunit has either inhibit or stimulate adenylte kinase or phopholipase C
 𝛽, 𝛾 subunit are homogenous
 Acts as transducer
o At rest G protein form complex with GDP
o When hormone bind to the receptor, causing 𝛼-subunit to bind with GTP release the 𝛽-
subunit and 𝛾-subunit

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 o 𝛼-subunit and GTP complex are active, stimulate or inhibit the phospholipase C or
adenylate cyclase depend on the characteristic
o 𝛼-subunit has GTPase activity that hydrolyse GTP to GDP and 𝛽-subunit and 𝛾-subunit
will rebind to 𝛼-GDP complex
 Phospholipase C 2nd messenger; PIP2 → IP3 + DAG
 Adenylate cyclase 2nd messenger; ATP → cAMP

cAMP & protein kinase A

 Active site of the C subunit is protected by the R subunit

 Binding of 2 molecule of cAMP to each R subunit, release the C subunit and exposed its active
site
 Activated C subunit involve in phosphorylation of enzyme

IP3/DAG & protein kinase C

 Phospholipase C 2nd messenger; PIP2 → IP3 + DAG

 IP3 bind to receptor at the Ca2+ storage cause Ca2+ release, ↑ cytosolic Ca2+
 Ca2+ activates protein kinase when it binds to calmodulin
 Protein kinase cause phosphorylation of protein for intracellular response
 DAG at the membrane activate PKC, with Ca2+ as cofactor

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  PKC cause phosphorylation of protein for intracellular response

Differences between PKA and PKG

Protein Kinase A Protein Kinase G
Needs G protein as transducer no need transducer molecule
Activated by cAMP Activated cGMP
2 regulatory subunit No subunit
2 catalytic subunit

Tyrosine kinase
 when insulin receptor bind to the receptor, causing auto-phosphorylation of tyrosine residue at
tyrosine kinase
 tyrosine kinase activated, cause futher phosphorylation of protein,
o activate kinase cascade, translocation of GLUT 4 to the membrane, uptake of glucose
o mitogenesis
 activates phospholipase C; GPI → IPG, activates phosphatase, dephosphorylation
o lipid synthesis
o glygonenesis

Thyroid hormone
 hydrophobic, able to diffuse through the cell membrane, does need membrane receptor
 interacts with specific receptor in cytosol to change metabolic and rate of gene expression
 thyroid hormone bind to repressor protein,
 prevent repressor protein from inhibit mRNA synthesis
 hormone bind to repressor receptor → no inhibition → more gene expression

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