ENDOCRINE SYSTEM

BERNARD MBITHI
The endocrine system
• Comprises a group of ductless glands that
secrete chemical messenger substances,
called hormones, into the bloodstream.
• Hormones are responsible for the
longterm regulation of many bodily
functions.
• Two types of glands: Exocrine, Endocrine
Major Glands of the Endocrine System
• Hypothalamus
• Pituitary Gland-Anterior and Posterior
• Thyroid Gland, Parathyroid gland
• Pineal Gland, Thymus
• Adrenal Gland-Adrenal Cortex, Adrenal
Medulla
• Pancreas (Pancreatic Islets)
• Testes, Ovaries
Overview of the Endocrine System
 Hormones

• Hormones are specialized chemical

substances that are produced by
particular ductless internal glands of the
body (or groups of secretory cells), and
then discharged directly into the
 bloodstream (in response to a stimulus)
by a process of endocrine secretion.
Hormones
• Carried via the circulation to other parts
of the body where, in extremely small
quantities
• They exert specific regulatory effects on
their selected ‘target’ cells, which
possess particular recognition features
(hormone receptors).
• Some hormones however, act more
generally in the body, rather than on a
specific target tissue.
 Hormones

• Hormones activate target cells depending

upon the chemical nature of the
hormone.
1. Lipid-soluble hormones diffuse through
the cell membranes of target cells.
• The hormones then binds to a receptor
protein that, in turn, activates a DNA
segment that turns on specific genes.
Hormones
• The proteins produced as result of the
transcription of the genes and
subsequent translation of mRNA act as
 enzymes that regulate specific
physiological cell activity.
Hormones
2. Water-soluble hormones bind to a
receptor protein on the plasma membrane
of the cell. The receptor protein, in turn,
stimulates the production of one of the
following second messengers:
• Cyclic AMP (cAMP) is produced when the
receptor protein activates another
membranebound protein called a G protein. The
G protein activates adenylate cyclase, the
enzyme that catalyzes the production of cAMP
from ATP.
 Hormones

• Cyclic AMP then triggers an enzyme that

generates specific cellular changes.
• Inositol triphosphate (IP3) is produced
from membrane phospholipids. IP3, in
turn, triggers the release of CA2+ from
 the endoplasmic reticulum, which then
activates enzymes that generate cellular
changes.
Hormone receptors
• Down-regulation: Decrease in the number
of receptors on the surface of target cells,
making the cells less sensitive to a
 hormone - e.g insulin receptors may be
down regulated in type 2 diabetes
Hormone receptors

• Up-regulation: increase in the number of

receptors which causes the cell to be
more sensitive to a particular hormone-
 e.g increase in uterine oxytocin receptors
in 3rd trimester promoting the
contraction of the smooth muscle of the
uterus
Hormones

• Hormones are:
–Mostly proteins, amines or steroids
–Secreted by endocrine glands-ductless
–Carried in bloodstream to target organs
–Change the way in which cells function
–Target specific
 Hormones
• Chemically, hormones may be classified
into three main groups
–Amino acids- derivatives (from the
adrenal medulla and thyroid gland)
–Steroids, structurally related to
cholesterol (from the sex glands and
the adrenal cortex)
–Proteins/polypeptides (from the
pancreas and pituitary gland).
 Hormones
• Many polypeptide hormones are
synthesized and stored by the endocrine
cell as inactive longer chain
‘prohormones’, from which the hormone
itself is eventually released by enzymatic
cleavage.
• As a means of communication between
cells, the endocrine hormonal
Water-soluble hormones

• Hormones that are soluble in water

include molecules that are composed of
amino acids.
• Because these hormones are soluble only
in water, they cannot pass through the
lipid plasma membrane.
Water-soluble hormones
• Water-soluble hormones that serve as
first messengers in this system include:
epinephrine, norepinephrine (NE),
 antidiuretic hormone (ADH), oxytocin
(OT), calcitonin (CT), and parathyroid
hormone (PTH).
Lipid-soluble hormones
• Hormones that dissolve in lipids include
mainly steroid hormones.
• Because the plasma membrane is
composed of a bilayer of lipid molecules,
steroid hormones can pass directly
through it by diffusion to enter the target
cell quite easily. (recall that steroids are a
type of lipid also; lipids dissolve in other
lipids).
 Lipid-soluble hormones
• Lipid-soluble hormones activate genes to
synthesize new proteins and enzymes.
• The protein products that are newly
formed include enzymes that promote
the metabolic activities specified by the
hormone.
• Lipid-soluble hormones that stimulate
protein synthesis include aldosterone,
cortisol, testosterone, estrogen, and
thyroxine.
 Control of Hormone secretion

• In order to maintain the correct

regulatory function of a hormone, the
endocrine gland should receive constant
feedback information about the state of
the system being regulated, so that
 hormone release can be finely adjusted
(closed-loop system).
Control of Hormone secretion
• The secretory activity of most endocrine
target organs is controlled by the
anterior pituitary, which is in turn, under
the influence of hypothalamic releasing
 hormones/factor’s released by
hypothalamic nerve fibres into the
pituitary blood supply.
Hormone Secretion and Distribution
• Distributed widely in the circulation
–Most hormones travel free in solution
 –Steroid, thyroid hormones bind to blood
proteins for transport
• Hormones are inactivated by –Binding
to cell receptors
–Removal by liver, kidney cells
–Breakdown by extracellular enzymes
 Hormonal control
• Feedback control-how does an endocrine
gland “know” how much hormone to
produce and release?
• This information, or feedback, is provided
by way of chemical signals that are sent
to the endocrine gland.
• There are two systems that operate in
this manner: negative feedback systems
and positive feedback systems.
Direct Negative feedback mechanism
• This is the most common ‘closed-loop’
control mechanism, in which an increase
in the level of a circulating hormone,
 decreases the secretory activity of the
cells producing it.
Direct Negative feedback mechanism
• In this typical hierarchical arrangement,
specialized groups of nerve cells in the
hypothalamus synthesize specific
peptides (releasing hormones) that are
secreted into the capillary network
feeding the anterior pituitary gland, and
then stimulate the pituitary cells to
release specific trophic hormones.
 Direct Negative feedback mechanism

• These peptides, in turn, stimulate their

particular target gland cells to release a
target gland hormone into the general
circulation. The latter then exerts a
negative feedback effect on the anterior
 pituitary, to regulate the level of trophic
hormone release.
Direct Negative feedback mechanism
• E.g: The secretion of thyroxine by the
thyroid gland is directly controlled by the
pituitary trophic hormone TSH . A high
blood level of thyroxine diminishes the
output of TSH, so that the activity of the
thyroid gland decreases (and vice versa).
Similar feedback mechanisms govern the
secretory activity of other target organs.
Direct negative feedback
Indirect negative feedback mechanism

• The target gland hormone inhibits the

release of pituitary trophic hormone
indirectly, by inhibiting the secretion of
hypothalamic releasing hormone. This
type of mechanism appears particularly
important in regulating adrenal and
 gonadal (testicular and ovarian) hormone
secretions.
Indirect negative feedback mechanism
• E.g: The corticosteroid hormones secreted
by the adrenal gland may indirectly inhibit
the release of corticotrophin (ACTH) from
the anterior pituitary, by inhibiting the
release of corticotrophin releasing
hormone . In addition, the trophic
hormone itself (ACTH) may act back
directly on the hypothalamic neurones to
ultimately inhibit its own release (‘short
loop’ feedback)
Indirect negative feedback
 Positive Feedback
• Such a mechanism is less common, and
tends to be intrinsically unstable, as it
attempts to increase rather than stabilize
the level of a circulating hormone.
• A hormone may either facilitate its own
release directly, by acting on the anterior
 pituitary, or indirectly by stimulating
hypothalamic hormone release.
Positive feedback
• Regulate hormone secretion by providing
a response in the same direction as the
stimulus.
• When the desired response stimulated
by hormone action occurs, a chemical
feedback signal causes the endocrine
gland to increase its rate of hormone
release and more responses are
stimulated.
 Positive feedback
• E.g: Production of oxytocin by the
pituitary gland during childbirth
stimulates contractions of the uterus.
• Its rising levels in the blood cause the
formation of products that stimulate
further oxytocin production, and uterine
 contractions respond by gradually
increasing in strength until birth is
accomplished.
Control of Endocrine Secretion
• Humoral (fluid) stimuli-E.g., blood level
of Ca2+ directly controls parathyroid
hormone and calcitonin release
• Hormonal stimuli-E.g., thyroid
stimulating hormone triggers thyroid
hormone release
• Neural stimuli-E.g., epinephrine release
from adrenal gland
 Hypothalamus

• Location: lies below the thalamus

• Primary Hormones: No one specific
hormone; called the “gate-keeper”
regulating the release and inhibition of
hormones
• Functions: “gate-keeper” role; regulates
pituitary
Hypothalamus and Endocrine Control

• Three mechanisms of action

–Hypothalamus secretes hormones as an
endocrine organ
–Hypothalamus secretes regulatory
hormones to control pituitary
gland endocrine cells
–Autonomic centers exert direct neural
control of adrenal medullae
 Gonadotrophin Releasing Hormone

• GnRH (also known as luteinizing hormone

releasing hormone (LHRH) or
gonadorelin) is released in a pulsatile
fashion from hypothalamic GnRH
neurones.
 Gonadotrophin Releasing Hormone

• Although other hypothalamic and/or

gonadal peptides may be involved, both
LH) and FSH release is most likely
promoted by a single releasing hormone
(GnRH), whose production can be
 inhibited by circulating oestrogens
(indirect negative feedback).
Corticotrophin Releasing Hormone
• Corticotrophin releasing hormone ( CRH)
(also referred to as corticotrophin
releasing factor, CRF) is a 41 amino acid
 peptide, responsible for controlling the
secretion of corticotrophin (ACTH).
Corticotrophin Releasing Hormone
• This action can be influenced by several
other substances:
–Glucocorticoid hormones - inhibit the
releasing effect of CRH on the pituitary
corticotrophs
–Vasopressin, oxytocin , or adrenaline
which potentiate it.
Thyrotrophin Releasing Hormone
• TRH promotes the release of
thyrotrophin (TSH)
• It also promotes the secretion of
pituitary prolactin.
Prolactin-Releasing/Inhibiting Factors
• Prolactin can also be released by several
other endogenous peptides e.g. oxytocin,
 vasoactive intestinal polypeptide, and
angiotensin-II .
• The prolactin release-inhibiting factor is a
simple non-peptide, dopamine, that is
released into the portal blood supply by
specific dopaminergic neurones
originating in the hypothalamus.
 Prolactin-Releasing/Inhibiting Factors

• This inhibitory action of dopamine,

effectively maintains prolactin secretion
at a minimal level, until required during
lactation, or release in response to stress.
Growth Hormone Releasing Hormone
• GHRH (somatocrinin) is responsible for
stimulating the synthesis and release of
pituitary growth hormone (GH).
• A hypothalamic GH-release inhibiting
hormone, somatostatin ( somatotrophin
release inhibiting hormone) is an amino
acid peptiede with a powerful receptor
mediated (non-competitive), inhibitory
effect on the action of GHRH on anterior
pituitary somatotrophs
Growth Hormone Releasing Hormone

• It is also capable of inhibiting the basal

secretion of TSH and prolactin from
the pituitary gland.
Pituitary gland
 The Pituitary Gland
• Also called the hypophysis • Releases
nine important hormones
–All are peptide hormones
–All bind to membrane (extracellular)
receptors
 The Pituitary Gland
• Anterior Pituitary Gland
–Controlled by regulatory hormones
from hypothalamic neurons
–Hypophyseal portal system transports
hypothalamic hormones directly to
anterior pituitary target cells
 –Regulated by negative feedback control
Anterior Pituitary Hormones
• Thyroid-Stimulating Hormone
(TSH)Triggers thyroid hormone release
• Adrenocorticotropic Hormone -Stimulates
glucocorticoid release from adrenal gland
• Follicle-Stimulating Hormone
(FSH)Stimulates estrogen secretion, egg
production (females), sperm production
(males)
 Anterior Pituitary Hormones
• Luteinizing Hormone (LH)- Triggers
ovulation, progestin production (females),
androgen production (males)
• Prolactin (PRL)-Stimulates mammary
gland development and milk secretion
• Growth hormone (hGH)-Stimulates cell
growth via somatomedins released from
liver
• Melanocyte Stimulating Hormone (MSH)
•Negative
Feedback
Control of
Endocrine
Secretion
 Posterior Pituitary Gland
• Releases hormones from hypothalamic axons
–Antidiuretic Hormone (ADH)
• Reduces water loss in the urine
• Increases thirst –Oxytocin
• Stimulates uterine contraction, milk delivery
• Stimulates prostate gland smooth muscle
Pituitary Hormones and Their Targets
 The Thyroid Gland
• Thyroid Follicles and Thyroid Hormones
– Follicles produce and store colloid
– Production requires adequate iodine in the diet
– Occurs in two forms, thyroxine (T4) and
triiodothyronine (T3)
– Increases metabolism and heat production
(calorigenic effect)
 – Required for normal development
Thyroxine hormone

• Increases BMR : The homone increases

O2 consumption in most of the body
tissues resulting in increased heat
production hence thermoregulation
 Thyroxine hormone
• Promotes Carbohydrate metabolism:
increase in gastrointestinal glucose
absorption, synthesis of metabolic
enzymes and increase in tissue sensitivity
to catecholamines, insulin and growth
hormone.
• Net result -increased gluconeogenesis and
glycogenolysis in the liver, and glucose
utilization by fat, liver and muscle cells.
Thyroxine hormone
• Promotes Protein metabolism: leading
to significant weight loss and elevation in
plasma amino acid levels.
• Stimulates fat metabolism: along with
an increased oxidation of free fatty acids.
• Maturation of the CNS: Thyroid
hormones are essential for normal CNS
development during late foetal and early
postnatal life
 Thyroxine hormone

• Skeletal Growth and Maturation:

actions of thyroid hormone are
synergistic with those of growth
hormone, hence normal bone growth
and maturation, and the eventual
development of normal adult stature.
 The Parathyroid Glands
• Four glands embedded on thyroid
posterior
• Chief cells produce parathyroid
hormone
2+
• Low blood Ca triggers secretion
 Parathyroid hormone

• Causes a rapid increase in distal tubular

2+ 2+
reabsorption of Ca and Mg from the
glomerular filtrate, and increases the
excretion of phosphate in the urine
 Parathyroid hormone

• Promotes the formation of the active

vitamin D metabolite 1α, 25-
dihydroxycholecalciferol (1,25-(OH) 2D3)
within the kidney tubular cells, which in
turn, facilitates the release of Ca2+ from
 bone and enhances the rate of
absorption of Ca2+ from the small
intestine and the kidney.
Parathyroid hormone
• Stimulates rapid efflux of Ca2+ from the
calcium pool in the bones into the
extracellular fluid (facilitated by 1, 25-
 (OH)2D3)
• Stimulates osteoclast bone cells to
release calcium and phosphate through
bone dissolution or resorption
• Eventually, osteoblast cells are stimulated
to synthesize new bone matrix.
 Parathyroid hormone
2+
• Stimulates intestinal absorption of Ca
and phosphate, mediated by the vitamin
D metabolite 1,25-(OH)2D3
• Stimulates the activity of the enzyme
1αhydroxylase involved in the
production of
1,25-(OH)2D3 in the kidney
 Increased excretion
of calcium
in kidneys
Thyroid gland
Blood calcium
produces
levels decline
calcitonin Calcium deposition in
bone (inhibition
of osteoclasts)
Uncertain significance
in a healthy
nonpregnant adult

HOMEOSTASIS
DISTURBED HOMEOSTASIS
Rising calcium RESTORED
levels in blood HOMEOSTASIS
Normal calcium
levels
HOMEOSTASIS (8.5-11 mg/dl)
DISTURBED HOMEOSTASIS
Falling calcium RESTORED
levels in blood
Release of stored
calcium from bone
(stimulation of
osteoclasts, inhibition
of osteoblasts)

Parathyroid Enhanced Blood calcium

glands secrete reabsorption levels
parathyroid of calcium in kidneys increase
hormone (PTH)
Stimulation of
calcitriol production
at kidneys;
enhanced Ca2+, PO43-
absorption by
digestive tract
HOMEOSTASIS
DISTURBED
Rising calcium
levels in blood HOMEOSTASIS
levels
(8.5-11 calcium
Normal mg/dl)
 Thyroid gland
produces
calcitonin

HOMEOSTASIS
DISTURBED
Rising calcium
levels in blood HOMEOSTASIS
levels
(8.5-11 calcium
Normal mg/dl)
 Increased excretion
of calcium
in kidneys
Thyroid gland
produces
calcitonin

HOMEOSTASIS
DISTURBED
Rising calcium
levels in blood HOMEOSTASIS
levels
(8.5-11 calcium
Normal mg/dl)
 Increased excretion
of calcium
in kidneys
Thyroid gland
produces Blood calcium

calcitonin Calcium deposition in levels decline

bone (inhibition
of osteoclasts)
HOMEOSTASIS
DISTURBED

Rising calcium levels in blood

HOMEOSTASIS

levels
(8.5-11 mg/dl)
Normal calcium

levels
(8.5-11 mg/dl)
 Increased excretion
of calcium
in kidneys

Blood calcium
levels decline
Calcium deposition in
bone (inhibition
of osteoclasts)

Uncertain significance
in a healthy
nonpregnant adult

HOMEOSTASIS
RESTORED
HOMEOSTASIS levels
Normal calcium (8.5-11 mg/dl)
 HOMEOSTASIS
Normal calcium
levels
HOMEOSTASIS (8.5-11 mg/dl)
DISTURBED
Falling calcium
levels in blood
 HOMEOSTASIS
Normal calcium
levels
HOMEOSTASIS (8.5-11 mg/dl)
DISTURBED
Falling calcium
levels in blood

Parathyroid
glands secrete
parathyroid
hormone (PTH)
 HOMEOSTASIS
Normal calcium
levels
HOMEOSTASIS (8.5-11 mg/dl)
DISTURBED
Falling calcium
levels in blood
Release of stored
calcium from bone
(stimulation of
osteoclasts, inhibition
of osteoblasts)

Parathyroid
glands secrete
parathyroid
hormone (PTH)
Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings 9 of 13
 HOMEOSTASIS
Normal calcium
levels
HOMEOSTASIS (8.5-11 mg/dl)
DISTURBED
Falling calcium
levels in blood
Release of stored
calcium from bone
(stimulation of
osteoclasts, inhibition
of osteoblasts)

Parathyroid Enhanced
glands secrete reabsorption
parathyroid of calcium in kidneys
hormone (PTH)
 HOMEOSTASIS
Normal calcium
levels
HOMEOSTASIS (8.5-11 mg/dl)
DISTURBED
Falling calcium
levels in blood
Release of stored
calcium from bone
(stimulation of
osteoclasts, inhibition
of osteoblasts)

Parathyroid Enhanced Blood calcium

glands secrete reabsorption levels
parathyroid of calcium in kidneys increase
hormone (PTH)
Stimulation of
calcitriol production
at kidneys;
enhanced Ca2+, PO43-
absorption by
digestive tract
 HOMEOSTASIS
Normal calcium
levels
HOMEOSTASIS (8.5-11 mg/dl)
DISTURBED HOMEOSTASIS
Falling calcium RESTORED
levels in blood
Release of stored
calcium from bone
(stimulation of
osteoclasts, inhibition
of osteoblasts)

Parathyroid Enhanced Blood calcium

glands secrete reabsorption levels
parathyroid of calcium in kidneys increase
hormone (PTH)
Stimulation of
calcitriol production
at kidneys;
enhanced Ca2+, PO43-
absorption by
 Increased excretion
of calcium
in kidneys
Thyroid gland
Blood calcium
produces
levels decline
calcitonin Calcium deposition in
bone (inhibition
of osteoclasts)
Uncertain significance
in a healthy
nonpregnant adult

HOMEOSTASIS
DISTURBED HOMEOSTASIS
Rising calcium RESTORED
levels in blood HOMEOSTASIS
Normal calcium
levels
HOMEOSTASIS (8.5-11 mg/dl)
DISTURBED HOMEOSTASIS
Falling calcium RESTORED
levels in blood
Release of stored
calcium from bone
(stimulation of
osteoclasts, inhibition
of osteoblasts)

Parathyroid Enhanced Blood calcium

glands secrete reabsorption levels
parathyroid of calcium in kidneys increase
hormone (PTH)
Stimulation of
calcitriol production
at kidneys;
enhanced Ca2+, PO43-
absorption by
digestive tract
The Adrenal Glands
 Adrenal gland anatomy
–Lie along superior border of each
kidney
–Surrounded by fibrous capsule
–Made of two parts
•Adrenal cortex (outer)
 •Adrenal medulla (inner)
The adrenal glands
• Adrenal Cortex-synthesizes steroid
hormones (corticosteroids)
•Glucocorticoids (e.g., cortisol) –
Stimulated by ACTH
–Affect glucose metabolism
•Mineralocorticoids (e.g., aldosterone)
–Stimulated by angiotensin II
+
–Restricts loss of water &Na
•Androgens (male hormone)
 The adrenal glands
• The adrenal secretion of sex steroids
(testosterone,
dehydroepiandrosterone, oestradiol,
and progesterone) - small and
physiologically insignificant, compared
 with the testicular and ovarian
secretion of these hormones
• In females, the growth of axillary and
pubic hair is dependent on adrenal
androgen secretion.
 Control of Release
• Adrenal steroids are not stored within
the adrenocortical cells in significant
amounts, but are liberated as soon as
they are synthesized.
• The rate of glucocorticoid synthesis and
secretion (principally cortisol) is
 controlled by ACTH under negative
feedback control.
Control of Release
• Effects of ACTH on adrenal cells are
mediated by specific membrane receptors
linked to intracellular cyclic AMP
production.
• ACTH - necessary for normal growth and
maintenance of the adrenal cortex
• Cortisol secretion shows a circadian
rhythm (24 hour periodicity)- highest
blood levels -in the morning, before
waking
 Control of release
• Aldosterone secretion, is mediated by the
rennin-angiotensin system.
• Both glucocorticoids &mineralocorticoids
are bound to plasma proteins (mainly
transcortin— an α2-globulin, and albumin)
 leaving only about 10% free and
metabolically active
• Aldosterone also has a specific binding
globulin
A. Adrenal hormones- Glucocorticoids
• Cortisol - principal glucocorticoid
Main actions
• Control of carbohydrate, protein and fat
metabolism.
• Suppression of tissue inflammation in
response to injury.
• Suppression of immune responses
• Increases body ability to withstand
various noxious stimuli (stresses).
 i. Carbohydrate Metabolism
• Cortisol stimulates gluconeogenesis from
circulating amino acid precursors, and
promotes the storage of liver glycogen
• The effects are accomplished by the
induced production of additional
 metabolic enzymes involved in
gluconeogenesis and glycogen synthesis.
• Cortisol also antagonizes the action of
insulin on glucose uptake into muscle and
adipose
 ii. Protein Metabolism
• Cortisol inhibits amino acid uptake and
protein synthesis in peripheral tissues.
• It promotes protein breakdown in
muscle, skin and bone, with consequent
release of amino acids into the blood
(utilized for gluconeogenesis).
 ii. Protein Metabolism

• The synthesis of glucose thus occurs at

the expense of protein catabolism.
• Excess cortisol can therefore lead to
muscle wasting as well as loss of protein
(collagen) from the skin and capillary
 walls (increased tendency to bruise) and
bone matrix.
iii. Fat (Lipid) Metabolism
• Cortisol stimulates lipolysis in adipose
tissue, with release of fatty acids and
glycerol (for gluconeogenesis), while
inhibiting fat synthesis.
• Excess cortisol may cause an unusual
redistribution of body fat with increased
deposition in the face and trunk, and
between the shoulders
Principal metabolic actions of cortisol
2. Anti-Inflammatory & Immunosuppression
• Cortisol (and other glucocorticoids) when
administered at relatively high
pharmacologic doses, inhibit the normal
inflammatory process which occurs when
tissue is damaged.
• This action underlies the therapeutic use
of corticosteroids in the treatment of
certain chronic inflammatory conditions
5. Response to Stress
• Unfavourable stresses e.g acute trauma,
pain, cold, fever or emotional stimuli can
increase plasma cortisol - to protect the
 body against these stressful circumstances
- increasing blood levels of glucose and
free fatty acids for energy sources
6. Response to Stress
• Pronounced inhibition of production of
cytokines & other inflammatory/immune
mediators by glucocorticoids, may be an
important component of the ‘stress
protection’ response, by preventing
stressinduced defense reactions from
‘overshooting’ and becoming potentially
damaging to the host
 B. Mineralocorticoids
• Aldosterone is the principal potent
mineralocorticoid
• Mineralocorticoids can also possess
some glucocorticoid activity (and vice
versa).
 Actions of aldosterone
[Link] of body sodium and
excretion of potassium: Aldosterone
increases Na+ reabsorption while
promoting excretion of K+ and H+ across
epithelial cell walls in the distal convoluted
tubule and collecting ducts of the kidney.
• The resultant decrease in Water excretion
(by passive tubular reabsorption),
increases blood volume.
Actions of aldosterone
[Link] in the ratio of Na+ to K+
concentrations in sweat and in saliva:
the increased inward transport of Na+
 (with passive efflux of K+) occurs across
the epithelial cell membranes of sweat
and salivary gland ducts.
[Link] in the reabsorption of Na+ from
the colon, and increased excretion of K+
in the faeces.
Control of release of aldosterone
• Mainly influenced by the
reninangiotensin system and the plasma
sodium and potassium concentrations.
 Control of release of aldosterone
• Renin-Angiotensin System: Renin is a
proteolytic enzyme released by
specialized juxtaglomerular cells (situated
within the afferent arteriolar walls of the
kidney) when there is a fall in renal blood
pressure and an excessive reduction in
circulating blood volume (e.g. during
haemorrhage, salt or water loss).
 Control of release of aldosterone
• Circulating renin promotes the
production of an inactive angiotensin I
from angiotensinogen (derived from the
liver).
• Angiotensin I is rapidly converted in the
lung and plasma (via the
angiotensinconverting enzyme; ACE) to
 Control of release of aldosterone
the active angiotensin II, which directly
stimulates the synthesis and release of
aldosterone from the adrenal cortex.
• Angiotensin II has a potent, direct
vasoconstrictor action that helps to
maintain the BP of the arterial
 Control of release of aldosterone
circulation under extreme conditions,
and to control water intake
• Circulating angiotensin II is degraded by
angiotensinase enzymes to angiotensin
III and ultimately to angiotensin IV ,
which has less potent, though similar
vasoconstrictor and
 Control of release of aldosterone
aldosteronereleasing actions to
angiotensin II.
• Plasma Na+ and K+ Concentrations:
Large decrease in plasma Na+ or a small
increase in plasma K+ concentration
stimulates the synthesis and release of
aldosterone by a direct action on the
 Control of release of aldosterone
biosynthetic enzymes in the adrenal
cortex.
 The adrenal glands
• Adrenal Medulla-Produces two related
hormones: Epinephrine (adrenaline),
Norepinephrine (noradrenaline)
–Increases heart rate and force,
releases glucose, fatty acids into
blood, opens airways
The Adrenal Glands
 The Pineal Gland
• Synthesizes melatonin
–Inhibits reproductive function
–Protects neural tissue from free
radicals
–Establishes daily wake-sleep cycle
The Pancreas
 The Pancreas
• Has both exocrine and endocrine cells
• Endocrine cells organized into islets
of Langerhans
• Islet cells secrete insulin and
glucagon –Insulin produced by beta
cells
–Glucagon produced by alpha cells
• Exocrine cells secrete enzyme-rich
digestive fluid
 The pancreas
• Actions of Insulin and Glucagon
• Insulin
–Lowers blood glucose concentration
–Increases glucose uptake, storage, and
use by target cells
–Targets liver, muscle, fat cells
 The pancreas
–Glucagon
•Raises blood glucose concentration
•Increases glycogen breakdown and
glucose synthesis
•Targets liver cells
 Control of insulin release
• Blood glucose concentration: One of the
major physiological determinants of
insulin secretion by the β-cells, is the
level circulating glucose in the blood
• Glucagon and somatostatin: May also
influence insulin release indirectly by
modulating the levels of intracellular
cAMP
 Control of insulin release
• Gastrointestinal hormones: Several
hormones released from the GIT e.g.
gastrin, secretin, & cholecystokinin
stimulate insulin release directly.
• Amino acids and fatty acids: Arginine,
leucine and some other amino acids
derived from protein digestion are
 Control of insulin release
potent stimulators of insulin release-
these effects are generally synergistic
with those of glucose.
• An increase in free fatty acid levels also
promotes the secretion of insulin.
• Other hormones: Growth hormone ,
glucocorticoids and thyroid hormone
 Control of insulin release
may stimulate insulin release indirectly
by increasing the blood glucose level.
• Autonomic nervous system:
Parasympathetic nerve stimulation
increases insulin secretion while the
dominant effect of sympathetic nerve
stimulation is to inhibit release
 Insulin action
• Insulin is the only hormone with the
ability to directly lower the blood glucose
level.
• It promotes the storage of chemical
energy derived from food in the form of
glycogen, proteins and lipids , while
 suppressing catabolism of stored
nutrients
Insulin action

• Major target organs for insulin

actionliver, muscles and adipose tissue
 organs that are specialized for energy
storage.
• Some tissues of the body such as kidney,
brain, or red blood cells are less sensitive
or unresponsive to this hormone.
 Role of insulin in carbohydrate
metabolism
[Link] of glycogen synthesis in
skeletal muscle, liver and adipose tissue by
a direct increase in glycogen synthase and
a decrease in glycogen phosphorylase
activity.
Role of insulin in carbohydrate metabolism
• 2. Increase in hepatic glucose
phosphorylation (due to stimulation of
glucokinase activity), and a decrease in
glucose dephosphorylation (due to
inhibition of glucose-6-phosphatase
activity).
3. Increase in glucose metabolism
(glycolysis) with a simultaneous decrease
in liver gluconeogenesis.
Role of insulin in protein metabolism.
• Stimulates cellular active transport of
plasma amino acids into
 musclelowering blood amino acid
levels
• Stimulates muscle protein synthesis
directly, (anabolic action) while
depressing protein breakdown. The
lower levels of circulating amino acids
 contribute towards the overall
decrease in liver gluconeogenesis.
Role of insulin in fat metabolism
• Stimulates uptake of glucose into adipose
cells and promotes lipogenesis and
storage of fatty acids in the form of
 triglycerides in both adipose and hepatic
tissues
• Prevents lipolysis by inhibiting
hormonesensitive lipase activity in
adipose cells; the levels of circulating
free fatty acids are therefore reduced
 Glucagon
• Synthesized in pancreatic islet α-cells
from a larger preproglucagon precursor
molecule and stored in the form of
cytoplasmic granules
• Released from the islet cells (into the
portal circulation) by a process of
 2+
Ca dependent exocytosis, mediated by a
rise in the level of intracellular cAMP
Control of glucagon release
• Blood glucose concentration: An increase in
blood glucose level inhibits glucagon
release and vice versa.
• Other islet hormones: Glucagon release is
inhibited by both somatostatin and by
insulin
• Gastrointestinal hormones: cholecystokinin,
gastrin and gastric inhibitory peptide
stimulate glucagon release.
 Control of glucagon release
• Amino acids and fatty acids: Certain
amino acids, particularly arginine and
alanine stimulate glucagon secretion,
whereas increased levels of free fatty
acids cause an inhibition of its release
• Increased secretion of glucagon in
response to a proteinrich meal enables
the liver to dispose of the excess plasma
amino acids by gluconeogenesis.
 Control of glucagon release

• Autonomic nervous system: both

sympathetic and parasympathetic nerve
stimulation increase the secretion of
glucagon. Secretion is also enhanced by
stressful stimuli (e.g Vigorous exercise)
 most likely acting via the sympathetic
nervous system.
Principal actions of glucagon
• Increase in hepatic glycogenoly and
gluconeogenesis, leading to an increase
in production and release of glucose
into the blood.
• Increase in lipolysis and mobilization of
fatty acids (from triglycerides), resulting
in increased levels of circulating
ketoacids, and acetoacetate
Endocrine tissues of other organs
• Intestines-Secretes hormones to control
digestion
• Kidneys-Secretes three hormones
oCalcitriol—Stimulates calcium and
phosphate absorption in intestine
oErythropoietin (EPO)—Stimulates red blood
cell production by bone marrow
oRenin—Enzyme that leads to angiotensin II
that triggers aldosterone from adrenal
cortex
 Endocrine Tissues of Other Organs
• Heart-Specialized muscle cells secrete
atrial natriuretic peptide (ANP) to lower
blood volume or blood pressure
• Thymus-Secretes thymosins that control
immune system defenses
• Adipose tissue (fat cells)
 –Secretes leptin to control appetite
–Secretes resistin to reduce insulin
response
Endocrine Tissues of Other Organs
• Testis (male gonad)-Interstitial cells
secrete androgens (testosterone)
–Sustentacular cells secrete inhibin
• Ovary (female gonad)-Follicle cells
secrete estrogens and inhibin
–Corpus luteum cells secrete estrogens
and progesterone
• Placenta-Secretes several hormones in
pregnancy
SUMMARY
 Posterior pituitary gland
Gland Principle Action
hormones

Posterior pituitary Antidiuretic Regulates water

gland hormone (ADH) reabsorption
from kidneys
 Oxytocin Allows milk
letdown/suckling reflex
Initiates labor
Maternal behaviour

Anterior pituitary gland

Gland Principle Action
hormones
Anterior Thyroid stimulating Regulates thyroid gland
pituitary hormone (TSH)
Adrenocortico trophic Regulates adrenal cortex
hormone (ACTH)
Gonadotrophic hormones Regulates gonads
Follicle stimulating
hormone (FSH)
Luteinising hormone
(LH)
Growth hormone (GH) Regulates growth in
children
Prolactin Regulates milk
production
 Thyroid & parathyroid glands
Gland Principle Action
hormones
Thyroid Thyroxine Stimulates
metabolism/releases
glucose

Calcitonin Lowers blood calcium

Parathyroid Parathyroid Raises calcium levels
hormone

Pancreas
Gland Principle Action
hormones
Islets of Insulin Lowers blood
Langerhans Beta- sugar levels
cells

Alpha-cells Glucagon Raises sugar

levels

Adrenal gland
Gland Principle Action
 hormones
Adrenal cortex Mineralocorticoids e.g. Sodium metabolism
aldosterone

Glucocorticoids e.g. Stress response/glucose

cortisol metabolism

Gonadocorticoids e.g. Secondary sexual

testosterone characteristics

Adrenal medulla Adrenaline (epinephrine) Fight or flight response

Noradrenaline
(norepinephrine)
 The gonads
Gland Principle Action
hormones
Male gonads Testosterone Male secondary sexual
characteristics
The testes

Female gonads Oestrogen • Female secondary sexual

characteristics
The ovaries (estrogen)
• Development of the
endometrium
 Progesterone • Maintenance of
endometrium

Endocrine Hormones
Gland Hormones Functions

Thyroid Thyroxine Regulates metabolism

Calcitonin Inhibits release of calcium from the bones

Parathyroids Parathyroid hormone Stimulates the release of calcium from the bones.

Islet cells (in Insulin Decreases blood sugar by promoting uptake of glucose by cells.
the pancreas)
Glucagon Increases blood sugar by stimulating breakdown of glycogen in the liver.

Testes Testosterone Regulates sperm cell production and secondary sex characteristics.

Ovaries Estrogen Stimulates egg maturation, controls secondary sex characteristics.

 Progesterone Prepares the uterus to receive a fertilized egg.

Adrenal
Epinephrine Stimulates “fight or flight” response.
cortex
Adrenal Glucocorticoids Part of stress response, increase blood glucose levels and decrease
medulla immune response.

Aldosterone Regulates sodium content in the blood.

Testosterone (in both Adult body form (greater muscle mass), libido.
sexes)

Pineal gland Melatonin Sleep cycles, reproductive cycles in many mammals.