Facultad

de Ciencias Biolgicas
Departamento de Ciencias Biolgicas
Curso BIOL172

FISIOLOGA ENDOCRINA
REGULACIN DE LA CONCENTRACIN
DE LA GLUCOSA PLASMTICA
Pncreas endocrino

Dr. Rodrigo Astete

FUENTES:

Dieta
Hgado
Rin (menor, excepto en el ayuno prolongado)

GLUCOSA
PLASMTICA
GLICEMIA: 60-100 mg/dl

DESTINOS:

Faculta<vos (msculo, tejido adiposo, mayora de los

tejidos)
Obligatorios (SN, eritrocitos, mucosa intes<nal, tbulos
renales)
Hgado
Orina (slo si glicemia > 160 mg/dl)

PNCREAS EXOCRINO => ACINO: secreta jugos diges<vos al duodeno

PNCREAS ENDOCRINO => ISLOTES DE LANGERHANS: secretan insulina y glucagn
directamente a la sangre

ISLOTES DEL PNCREAS

Clulas : glucagn
Clulas : insulina
Clulas : somatosta<na
Clulas F o PP: polipp<do pancre<co

Clulas : 20%
Clulas : 65%
Clulas : 10%
Clulas F o PP: 5%

ESTRUCTURA DE INSULINA
B

Part IX / Endocrine Physiology

Glucose

Leucine

SECRECIN DE
INSULINA

GLUT2 transporter

Extracellular
space

Glucose enters the cell

via a GLUT2 transporter,
which mediates
facilitated diffusion of
glucose into the cell.

b Cell

cytosol
Glycolysis

The increased glucose influx

stimulates glucose metabolism,
leading to an increase in
[ATP]i or in [ATP]i/[ADP]i.

Glucokinase
Glucose-6-phosphate
ATP

The increased [ATP]i and/or

[ATP]i/[ADP]i inhibits an ATPsensitive K+ channel.

Pyruvate
CCK
ACh

Mitochondrion
H2O

Gq

Inhibition of this K+ channel

causes Vm to become more
positive (depolarization).

Citric
acid
cycle

CO2

KATP channel

ATP

PLC

Depolarization

PIP2
IP3

[Ca2+]

ER

Ca2+
Voltage-gated
Ca2+ channel

DAG
Protein
kinase C

[Ca2+]

PKC
Secretory
granules
Other modulators of secretion
act via the adenylyl cyclasecAMP protein kinase A pathway
and the phospholipase and the
phospholipase Cphosphoinositide
pathway.

The depolarization activates a

voltage-gated Ca2+ channel in
the plasma membrane.

The activation of this Ca2+

channel promotes Ca2+ influx,
and thus increases [Ca2+],
which also evokes Ca2+induced Ca2+ release.

PKA

cAMP

Gs

Glucagon
-adrenergic
agonists

ATP

AC

Gi

Somatostatin
galanin
-adrenergic
agonists

The elevated [Ca2+] leads to

+
and lrelease
into the de
niveles de K plasm<cos exocytosis
es<mulan
a secrecin
blood of insulin contained
within the secretory granules.
insulina
La insulina promueve la captacin de K +
Insulin

Relacin entre la glicemia y la secrecin de insulina

SECRECIN BIFSICA DE INSULINA

Receptor de insulina

! Receptor con ac<vidad catal<ca <rosina

kinasa

! Ac<vidad catal<ca depende de la unin de
insulina en dominios extracelulares

Luego de la autofosforilacin el receptor es internalizado, la insulina y el receptor

son degradados. As la insulina regula a la baja su propio receptor.

Mecanismo de accin de la insulina en msculo y adipocito

EFECTOS DE INSULINA


RPIDOS (SEG)

INTERMEDIOS (MIN)

RETARDADOS (HORAS O DIAS)

AUMENTO DE TRANSPORTADORES DE GLUCOSA

EFECTOS GENMICOS
Acciones de Insulina
Hgado

Msculo

Tejido adiposo

gluconeogenesis

captacin glucosa lipolisis

glicgenogenesis

captacin de aa

captacin de glucosa

gliclisis

protelisis

captacin de cidos
grasos libres

glicgenolisis
cetognesis

> 100 mg/dl

GLUCAGN
La accin principal del
glucagn es en el hgado.
Regula la produccin de
glucosa y es<mula la
cetognesis.

SECRECIN DE GLUCAGN

ACCIONES DEL GLUCAGN

SOBRE LOS TEJIDOS
GLUCAGN

GLUCOSA
PLASMTICA

R
G
AC

ATP

AMPc

PKA

ACTIVACIN E
INACTIVACIN
DE ENZIMAS

Acciones de Glucagn
Insulina: hipoglicemiante, anabolizante,
entrada de glucosa a las clulas.
Hgado

Glucagn

Glucagn: hiperglicemiante, catabolizante.

captacin de glucosa

Es<mula la glucogenlisis (glucgeno " glucosa)

Es<mula la gluconeogenesis (aminocidos " glucosa)

Es<mula la cetogenia (cidos grasos " cuerpos cetnicos)

Efectos del glucagn en el hgado

! # Glicgenolisis
! # Gluconeognesis
! # Liplisis

Glucagn antagoniza
las acciones de la
insulina

TEST DE TOLERACIA A LA GLUCOSA

Efecto de hormonas en el
metabolismo energ<co

Efectos de la Adrenalina
Pncreas

Glucosa

Adrenalina -

Clulas

Clulas

Insulina
Adrenalina +

Adrenalina +

Hgado

Glucagn

Glucosa
Glicerol

AG

Glicgeno

+
Adrenalina

Adrenalina +

Glicgeno

TG
Tejido adiposo

+
Adrenalina

Piruvato
Y lactato

Msculo

Efecto de los glucocor<coides

Glucosa

Hgado

Glicgeno

Adrenalina +

Glucosa +
GC
AA
Glicerol

AG

GC +

Gluconeognesis

Almacenamiento de glucgeno

AA
+
GC

Msculo

TG
Tejido adiposo

Degradacin de protena

Liplisis

Sntesis de protena

U<lizacin de glucosa

U<lizacin de glucosa

Facultad de Ciencias Biolgicas

Departamento de Ciencias Biolgicas
Curso BIOL172

FISIOLOGA ENDOCRINA
REGULACIN DE LA CONCENTRACIN
DEL CALCIO PLASMTICO
Dr. Rodrigo Astete

Calcio:

- rol estructural en tejidos rmes (huesos y dientes)

- roles regulatorios en vas metablicas y de sealizacin
Flujo diario de calcio y fosfato

Calcio y Fosfato en
la dieta

Tracto GI

Calcio plasm<co (10 mg/dl)

Riones
Heces
Orina

Huesos

Se hace necesario un control riguroso de su concentracin

en el medio interno.

Existen mecanismo homeost<cos:

& Intes<no.
& Hueso.
& Rin.


Existen reguladores:
& Parathormona.
& Vitamina D.
& Calcitonina.

Rol siolgico del Calcio

Coagulacin
sangunea

Transmisin
neuronal

Accvidad
enzimcca

Mineralizacin
del hueso

Calcio

Regulacin de
glndulas
endocrinas y
exocrinas

Contraccin
muscular

Preservacin
de la
membrana

Balance de Calcio
Dieta

Absorcin

(1000 mg)

(350 mg)

excreci
n

Calcio
plasmtico

Remodelaci
n sea
Resorp<on

800 mg excrecin heces

200 mg excrecin renal

Calcemia
10 mg/dL

80% Albmina
20% Globinas

Forma de calcio
biolgicamente ac<vo
(5 mg/dL)
Fosfato, sulfato,
bicarbonato,lactato,
citrato

Ca2+ libre= FISIOLGICAMENTE ACTIVO

Glndulas paracroideas

Parathormona

Amino terminal posee

actividad biolgica

Hormona del tipo peptdico.

Parathormona
!Secretada por las clulas principales (chief) del la
glndula para<roidea
!Hormona principal que protege contra la
hipocalcemia
!Clulas blanco:
& Rin
& Hueso
& Intes<no.

Regulacin de secrecin de PTH por concentracin de calcio plasm<co

ACCIONES DE LA HORMONA PARATIROIDEA

HUESO: ostelisis osteoccca
accvidad de los osteoclastos (liberacin hidroxiprolina)
accvidad de los osteoblastos

RION: reabsorcin de PO4-3 (fosfaturia)

(inhibicin del transportador Na+/PO4-3

en el tbulo proximal)

reabsorcin de Ca2+
(tbulo distal)

INTESTINO: accin indirecta mediada por calcitriol

1-hidroxilasa renal
No hay receptores de PTH en los osteoclastos, solo en osteocitos y osteoblastos

PTH has several important actions in the kidneys (see

Fig. 35.7). It stimulates calcium reabsorption in the thick
ascending limb and late distal tubule, decreasing calcium

Plasma calcium

Parathyroid glands
PTH secretion

sis. Second, CT hypersecretion, such as from thyroid tu

involving parafollicular cells, does not cause any overt p
lems. On a daily basis, CT probably only fine-tunes the
cium regulatory system.
The overall action of CT is to decrease both cal
and phosphate concentrations in plasma (Fig. 35.8).
primary target of CT is bone, although some lesser e

Plasma calcium
Plasma PTH

Parafollicular cells
CT secretion

Kidneys
Phosphate
1,25-(OH)2 D3
reabsorption
formation

Bone
resorption

Plasma CT

Calcium
reabsorption
Urinary excretion
of phosphate

Plasma
1,25-(OH)2 D3
Urinary excretion
of calcium

Kidneys
Phosphate
Calcium
reabsorption
reabsorption

Release of calcium
into plasma
Intestine
Calcium absorption

Plasma phosphate

Urinary excretion
of phosphate

Bone
resorpti

Urinary excretion
of calcium

Calciu
release

Plasma calcium

Figure 35.7 Effects of parathyroid hormone (PTH)

on calcium and phosphate metabolism. 1,25-(OH)2 D3,

Plasma phosphate

Plasma calcium

Figure 35.8 Effects of calcitonin (CT) on calcium

Sntesis de calcitrol
!La absorcin intes<nal de calcio aumenta por la hormona 1,25-
dihidroxicolecalciferol (1,25(OH)2D3) conocida como calcitriol o vitamina D
!Calcitriol se fabrica a par<r de vitamina D obtenida de la dieta o elaborada
por la piel por accin de luz solar sobre precursores

El PTH favorece sntesis de Calcitriol.

!Vitamina D frena la PTH por dos mecanismos:
&directa, por unin al receptor vitamina D en la para<roides
&indirecta, por inducir aumento de calcio srico

Regulacin de la expresin gnica de

PTH y su secrecin

SNTESIS Y
SECRECIN DE
VITAMINA D

7-DEHIDROCOLESTEROL
UV

COLECALCIFEROL
PTH
Ca2+

25-HIDROXICOLECALCIFEROL

1- HIDROXILASA

1,25-DIHIDROXICOLECALCIFEROL

RELACIN DE LA SECRECIN DE
CALCITRIOL V/S [Ca2+]plas. total

ACCIONES DE CALCITRIOL
INTESTINO: absorcin de Ca2+ y PO4-3

HUESO: ostelisis osteoccca
accvidad de los osteoclastos

RION: reabsorcin de Ca2+ y PO4-3

Las acciones del calcitriol son mediadas por su unin a un
receptor NUCLEAR (VDR). Este complejo hormona receptor
aumenta la expresin de: calbindina, bombas de calcio y canales
epiteliales de calcio

Absorcin intescnal de Calcio

requires several hours to appear.

Plasma calcium

Plasma PTH

Renal 1-hydroxylase activity

1,25-(OH)2 D3 formation
Plasma
1,25-(OH)2 D3

Kidneys
Phosphate
reabsorption

Bone
promotes PTH
action

Calcium
reabsorption

Intestine
Phosphate
absorption

Urinary excretion
of phosphate

Calcium
absorption

Urinary excretion
of calcium
Plasma phosphate

Plasma calcium

Figure 35.9 Effects of 1,25-dihydroxycholecalciferol [1,25-(OH)2 D3] on calcium and phosphate metabolism. PTH, parathyroid hormone.

as with a cast or paralysis, can result in localized osteoporosis

of the affected limb. Space flight can produce a type of disuse
osteoporosis resulting from the condition of weightlessness.
Most commonly, osteoporosis is associated with advancing age in both men and women, and it cannot be assigned to
any specific definable cause. For several reasons, postmenopausal women are more prone to develop the disease than are
men. Figure 35.10 shows the average bone mineral content
(as grams of calcium) for men and women versus age. Until
about the time of puberty, males and females have similar
bone mineral content. However, at puberty, males begin to
acquire bone mineral at a greater rate; peak bone mass in men
may be approximately 20% greater than that of women. Maximum bone mass is attained between 30 and 40 years of age
and then tends to decrease in both sexes. Initially this occurs
at an approximately equivalent rate, but women begin to
experience a more rapid bone mineral loss at the time of menopause (about age 4550 years). This loss appears to result
from the decline in estrogen secretion that occurs at menopause. Low-dose estrogen supplementation of postmenopausal women is usually effective in retarding bone loss without
causing adverse effects. This condition of increased bone loss
in women after menopause is called postmenopausal osteoporosis. A new mechanistic perspective links immune cells
to the etiology of postmenopausal osteoporosis as well as to
bone loss caused by many other endocrine conditions.
Rickets is a softening of bones in children,
potentially leading to fractures and
deformity.

Rickets is characterized by the inadequate mineralization of

new bone matrix, such that the ratio of bone mineral to matrix
is reduced. As a result, bones may have reduced strength and

Acciones de la calcitonina

(producido por clulas C de la glndula croides)

!

&
&

!

DISMINUYE LA CALCEMIA
Inhibe resorcin sea (R en osteoclastos)
Aumenta excrecin renal de calcio y fosfatos
ANALGSICA.

! ANTI-INFLAMATORIA.

Regulacin hormonal de la calcemia.

sis. Second, CT hypersecretion, such as from thyroid tumors

involving parafollicular cells, does not cause any overt problems. On a daily basis, CT probably only fine-tunes the calcium regulatory system.
The overall action of CT is to decrease both calcium
and phosphate concentrations in plasma (Fig. 35.8). The
primary target of CT is bone, although some lesser effects

Plasma calcium

Parafollicular cells
CT secretion

Plasma CT

Kidneys
Phosphate
Calcium
reabsorption
reabsorption

Urinary excretion
of phosphate

Plasma phosphate

Bone
resorption

Urinary excretion
of calcium

Calcium
release

Plasma calcium

Figure 35.8 Effects of calcitonin (CT) on calcium

and phosphate metabolism.

Facultad de Ciencias Biolgicas

Departamento de Ciencias Biolgicas
Curso BIOL172

FISIOLOGA ENDOCRINA

Funcin gonadal
Dr. Rodrigo Astete

El eje Hipotlamo-Adenohipsis-Gnadas
regula la secrecin de hormonas sexuales

ones (except

is controlled
ypothalamus
In contrast,
olled by hord hypothalareted within
ed, as shown
ary through
-hypophysial
ese releasing
dular cells to
ontrol is dis-

Hypothalamus

Optic chiasm
Mamillary body
Median eminence

Artery
Primary capillary
plexus
Hypothalamichypophysial
portal vessels

Posterior pituitary
gland

Sinuses
Anterior pituitary
gland

from many
Vein
n a person is
gnal is transFigure 754
ise, when a
Gonadotrofos
liberan
FSH y LH eportal
n repuesta
a GnRH
sing
or excitHypothalamic-hypophysial
system.
nsmitted into
ting pleasant

El eje Hipotlamo-Adenohipsis-Gnadas
regula la secrecin de hormonas sexuales
Internal and
environmental
scmuli

SNC

GnRH

Hipotlamo

Short-loop nega6ve feedback

KEY
Scmulus

Adeno-
hipsis

Integracng center
Eerent pathway
Eector

Los lazos de
retroalimentacin
pueden ser
nega6vo
o posi6vo

LH

Tissue response

FSH

Clulas
endocrinas

Hormonas pepodicas
y esteroidales

Gonads
(ovaries or testes)

Produccin de
gametos

GnRH es<mula la sntesis y secrecin de LH y FSH

Secrecin de gonodotropinas durante la vida

en hombres y mujeres

Las hormonas FSH y LH van a ejercer sus acciones

sobre los tessculos del aparato reproductor
Chapter 80masculino
Reproductive and Hormonal Functions of the Male
Urinary
bladder
Ampulla
Seminal
vesicle
Ejaculatory
duct
Bulbourethral
gland

Prostate
gland
Erectile
tissue

Vas deferens
Epididymis
Prepuce
Glans
penis

Seminiferous
tubules
Testis

Scrotum

Fisiologa reproduccva masculina

Papel de LH y FSH en la
funcin tes<cular

Espermatognesis
es<mulada por la FSH

La TESTOSTERONA
tambin es<mula la
espermatognesis

La accin de la LH es<mula la
secrecin de TESTOSTERONA

Relacin entre clulas de Leydig y Sertoli

ABP= protena que une andrgenos

Inhibina= factor de crecimiento transformante (TGF)

Principales funciones de la
testosterona
! Desarrollo del aparato reproductor
! Aumenta el espesor y la mineralizacin
sea.
! Es<mula la sntesis de protenas.
! Desarrollo de caracteres sexuales
secundarios.

Fisiologa reproduccva femenina

Androgenos entran a las cels
granulosas que convierten
androgenos en estrogenos

Maduracin del folculo y oocito

Clulas de la granulosa secretan
l q u i d o f o l i c u l a r r i c o e n
ESTRGENOS

FSH escmula el desarrollo

del folculo

La LH (principalmente) escmula la
ovulacin, y hace que las clulas
de la granulosa y teca secreten
PROGESTERONA

Las clulas se convierten en clulas lutenicas

(luteinizacin) por accin de LH. Estas clulas secretan
PROGESTERONA y ESTRGENOS

Retroalimentacin negacva del ESTRGENO y

PROGESTERONA sobre LH y FSH produce
involucin del cuerpo lteo

Relacin entre clulas de la teca y granulosas

Fase folicular: estradiol

Fase lutea: progesteronas

Las secreciones hormonales dependen de

feedbacks nega<vos y posi<vos

(a) Early to mid-follicular phase

(b) Late follicular phase and ovulacon

GnRH

(c) Early to mid-luteal

phase

(d) Late luteal phase

GnRH

GnRH

GnRH

Hypothalamus

Pituitary

Tonic secre6on
resumes

FSH

LH

FSH

FSH

Follicle

Follicle

Granulosa
cells

Granulosa
cells

Thecal
cells

Corpus luteum
(from ovulated
follicle)

Thecal
cells

FSH

LH

LH

Corpus
luteum
dies

New follicles
begin to
develop

secretes

Androgens

Inhibin

Androgens

Estrogens

LH

High estrogen
output

Estrogen and
progesterone

Estrogen
Progesterone
Inhibin

Small amount of
progesterone

LH

FSH

KEY

Ovum

Estrogen

Follicle
Inhibin

Scmulus

Corpus luteum

Progesterone

Integracng center
Eerent pathway
Tissue response

Principales funciones de los

estrgenos
! Proliferacin del endometrio y desarrollo
glandular
! Aumenta los depsitos de grasa
! Inicia el crecimiento de la mama y el
aparato productor de leche
! Desarrollo del aparato reproductor
! Es<mula la fusin de la epsis y disis.