THE MIGHTY MOLECULES:

The Physiology of the

Endocrine System
VIVIEN FE F. FADRILAN-CAMACHO, MD, MPH, FPAFP
Associate Professor

OBJECTIVES
At the end of the course, the students would be able
to:
To discuss the basic functions of the endocrine system
To discuss the structural and functional organization of
the endocrine system
To explain the physiologic mechanisms of the
endocrine system
To discuss the role of specific intrinsic and extrinsic
stimuli on the normal physiology of the endocrine
system
ENDOCRINE SYSTEM
second great control system of the body
interacts with the nervous system to coordinate
and integrate the activity of body cells
Nervous sytem = via electrochemical impulses; with
responses in milliseconds
Endocrine system = via hormones; responses
that occur after a lag period of seconds or
even daysonce initiated, more prolonged
ENDOCRINE SYSTEM: FUNCTIONS
Water balance: controls solute concentration of blood
Uterine contractions and milk release
Growth, metabolism and tissue maturation
Ion regulation
Heart rate and blood pressure regulation
Blood glucose control
Immune system regulation
Reproductive functions control
EXOCRINE VS ENDOCRINE GLAND
Exocrine gland glands with ducts; produce non-
hormonal substances membrane surface e.g.
sweat and salivary glands
Endocrine glands ductless glands which produce
hormones vascular and lymphatic drainage
- Pituitary , thyroid, parathyroid, adrenal, pineal and
thymus gland

ENDOCRINE SYSTEM
Hypothalamus
neuroendocrine organ
Organs with endocrine
and exocrine products:
- pancreas
- ovaries and testes
LOCAL CHEMICAL MESSENGERS
Autocrines exert effects on the same cells that
secrete them.
- e.g. prostaglandins smooth muscle cell
contraction
Paracrines act on surrounding cells
- e.g. somatostatin inhibits release of insulin release
produced by other cells


HORMONE RECEPTORS
Membrane Bound
Receptors
Receptor sites on the
outer surface of the cell
membrane
Interact with large and
water-soluble
molecules
HORMONE RECEPTORS
Membrane Bound Receptor Responses
1. Receptors that directly alter membrane permeability
- opening and closing of ion channels e.g. Ach and Na+
channels in skeletal muscle membranes
2. Receptors that directly alter the activity of enzymes
- or enzyme activities through or activity of cyclic
guanosine monophosphae (cGMP)

HORMONE RECEPTORS
3. Receptors and G proteins
- activation of G proteins
(complex proteins)
- inactive G protein with , ,
subunits
- GDP is bound to subunit
- Receptor bindingthe
subunit separates from the
and . GTP replaces GDP
can open or close
channels
activate enzymes
affect gene exporession

HORMONE RECEPTORS
Intracellular receptors
Located in the
cytoplasm or nucleus
of the cell
Interact with small,
lipid intercellular
signals

HORMONES
chemical substances
secreted by cells into the extracellular fluids
regulate the metabolic function of other cells in the
body

HORMONE ACTIONS
1. Alters plasma membrane
permeability or membrane
potential, or both, by opening
or closing ion channels
2. Stimulates synthesis of
proteins or regulatory
molecules such as enzymes
3. Activates or deactivates
enzymes
4. Induces secretory activity
5. Stimulates mitosis
HORMONES: CHEMICAL STRUCTURE
1. Proteins, peptides and amino acid derivatives
- Bind to membrane-bound receptors with exception to
the thyroid hormones which diffuse through
membranes and bind to intracellular receptors.
a. Proteins- most hormones of the anterior pituitary
glands
b. Peptide hormones hormones of the posterior
pituitary gland
c. Amino acid derivatives amino acids that have been
chemically modified; hormones of the adrenal
medulla



HORMONES: CHEMICAL STRUCTURE
2. Lipid hormones lipid soluble
a. Steroid hormones derived from cholesterol
- hormones produced by the adrenal cortex and
gonads
- diffuse across the cell membrane and bind to
intracellular receptor molecules
b. Eicosanoids from arachidonic acid
- include prostaglandins, prostacyclins and
leukotrienes
- boound to membrane bound receptors that are
associated with G proteins


HORMONE RESPONSES
Permissiveness - situation when one hormone cannot
exert its full effects without another hormone being
present e.g. thyroid hormone on reproductive system
Synergism -occurs where more than one hormone
produces the same effects at the target cell and their
combined effects are amplified (1+1 =2) e.g. glucagon
and epinephrine
Antagonism -one hormone opposes the action of
another hormone e.g. insulin and glucagon
NEGATIVE FEEDBACK MECHANISM
ensure a proper level of hormone activity at the
target tissue.
After a stimulus causes release of the hormone,
products resulting from the action of the hormone
tend to suppress its further release.
the hormone has a negative feedback effect to
prevent oversecretion of the hormone or
overactivity
POSITIVE FEEDBACK MECHANISM
occurs when biological action of the hormone
causes additional secretion of the hormone.
luteinizing hormone (LH) release as a result of the
stimulatory effect of estrogen on the anterior
pituitary before ovulation.
LH ovaries estrogen LH
After LH reaches an appropriate concentration
negative feedback

HORMONE CLEARANCE
(1) metabolic destruction by the tissues
(2) binding with the tissues
(3) excretion by the liver into the bile
(4) excretion by the kidneys into the urine
ENDOCRINE GLAND STIMULI
Humoral direct response to changing blood levels
e.g. parathyroid hormone, insulin and aldosterone
Neural stimulated by nerve fibers e.g.
catecholamines
Hormonal in response to hormones produced by
other endocrine organs e.g. hypothalamic-pituitary
axis
Fig 19.1 Endocrine System
HYPOTHALAMUS THE MASTER GLAND
regulates the NS and endocrine system activities
by 3 different mechanisms
1) by secreting regulatory hormones that control
endocrine cells in the adenohypophysis (anterior
lobe) of the pituitary gland:
- Releasing hormones (RH) stimulate production of
one or more hormones
- Inhibiting hormones (IH) prevent the synthesis and
secretion of specific pituitary hormones
THE MASTER GLAND
2) acts as an endocrine organ, releasing the hormones
ADH and oxytocin into the circulation at the
neurohypophysis (posterior lobe)

3) contains autonomic centers that have direct neural
control over the endocrine cells of the suprarenal
medulla sympathetic division is activated
medulla hormones

Hypothalamic Control over Endocrine Organs

THE PITUITARY GLAND
Pea on a stalk (infundibulum)
2 lobes: the adenohypophysis (anterior lobe) and the
neurohypophysis (posterior lobe)
Hypothalamus regulates secretions of anterior
pituitary
Posterior pituitary is an extension of the
hypothalamus
Anterior pituitary 9 major hormones that
Regulate body functions
Regulate the secretions of other endocrine glands


Pituitary Gland Structure
Posterior pituitary
(neurohypophysis):
extension of the nervous
system via the
infundibulum
Secretes neurohormones
Anterior pituitary
(adenohypophysis)
Consists of three areas with
indistinct boundaries: pars
distalis, pars intermedia,
pars tuberalis

THE PITUITARY GLAND
Posterior lobe connected to the hypothalamus via
the hypothalamic-hypophyseal tract
- paraventricular neurons oxytocin
- supraoptic neurons antidiuretic hormone (ADH)
Anterior lobe
- Hypophyseal portal system vascular connection
with the hypothalamus
- where releasing and inhibitory hormones are
secreted




Hormones of Posterior Pituitary: ADH
Antidiuretic hormone (ADH). Also called vasopressin.
A. Osmoreceptors (specialized neurons of
hypothalamus monitor changes in intercellular
osmolality (relative concentrations of electrolytes
and water). If the concentration of electrolytes
increases or if the concentration of water
decreases, then ADH secretion is stimulated.
B. Baroreceptors (specialized neurons found in walls
of atria of heart, large veins, carotid arteries,
aortic arch) sense changes in blood pressure (BP).
If BP decreases, then ADH secretion is stimulated.
Control of ADH Secretion
Control of Oxytocin Secretion
POMC
Propiomelanocortin (POMC)
- prohormone from the anterior pituitary
- source of ACTH, enkephalin, beta-endorphin,
lipotropin
- source of melanocyte-stimulating hormone CNS
neurotransmitter involved in appetite control
Melanocyte Stimulating Hormone,
Endorphins, and Lipotropins
ACTH, MSH, endorphins and lipotropins all derived
from the same large precursor molecule when
stimulated by CRH
MSH causes melanocytes to produce more melanin
Endorphins act as an analgesic; produced during
times of stress.
Lipotropins cause adipose cells to catabolize fat


Adrenocorticotrophic Hormone (ACTH)
CRH from hypothalamus causes release of
ACTH from anterior pituitary which

Causes cortisol secretion from the adrenal
cortex (a glucocorticoid from the zona
fasciculata) against stress
Causes aldosterone secretion from the adrenal
cortex (a mineralocorticoid from the zona
glomerulosa)
Binds directly to melanocytes of the skin;
causes increase in production of melanin.


Growth Hormone (GH or somatotropin)
Stimulates uptake of amino acids;
protein synthesis; growth in most
tissues.
Stimulates breakdown of fats to be
used as an energy source but
stimulates synthesis of glycogen:
glucose sparing
Promotes bone and cartilage
growth
Regulates blood levels of nutrients
after a meal and during periods of
fasting
Stimulates glucose synthesis by
liver
Regulation of GH Secretion
TSH (thyrotropin) and Thyroid Hormones
TRH from hypothalamus
causes the release of TSH
from anterior pituitary
which causes secretion and
storage of hormones T
3
and
T
4
from and within the
thyroid gland
T3 and T4 inhibit TRH and
TSH secretion
LH, FSH, Prolactin
Gonadotropins: glycoprotein hormones that promote
growth and function of the gonads
LH and FSH
Both hormones regulate production of gametes and
reproductive hormones
Testosterone in males
Estrogen and progesterone in females
GnRH from hypothalamus stimulates LH and FSH secretion
Prolactin: role in milk production
Regulation of secretion: prolactin-releasing hormone
(PRH) and prolactin-inhibiting hormones (PIH)
Thyroid Gland
Highly vascular
Iodine enters follicular cells
by active transport. Only
gland that stores hormone.
Histology
Composed of follicles:
follicular cells
surrounding
thyroglobulin/thyroid
hormones
Parafollicular cells:
between follicles
Follicular cells secrete thyroglobulin into lumen
of follicle.
- Iodine and tyrosine necessary for production
of T3 and T4.
- Hormones stored here attached to the
thyroglobulin then absorbed into follicular cells
- hormones disattached from thyroglobulin and
released into circulation.
Parafollicular cells -secrete calcitonin which
reduces [Ca2+] in body fluids when Ca levels
are elevated.
Thyroid Gland

Thyroid Hormones
Only free thyroxine and T
3
can enter cells;
bound-thyroxine serves as a reservoir of this
hormone
33-40% of T
4
converted to T
3
in cells
T
3
more potent
Bind with intracellular receptor molecules and
initiate new protein synthesis
Normal growth of many tissues dependent on
presence of thyroid hormones.
Effects of
T
3
and T
4

1. Maintain normal rate of metabolism.
2. Increase the rate at which glucose,
fat, and protein are metabolized.
3. Increase the activity of Na
+
-K
+
pump
which increases body temperature.
4. Can alter the number and activity of
mitochondria resulting in greater
ATP synthesis and heat production.
5. Normal growth and maturation of
bone, hair, teeth, c.t., and nervous
tissue require thyroid hormone.
6. Both T
3
and T
4
play a permissive role
for GH
REGULATION OF THYROID HORMONES
Regulation of Calcitonin Secretion
Produced by parafollicular cells
Secretion triggered by high Ca
2+
concentration
in blood; acts to decrease Ca
2+
concentration
Primary target tissue: bone
Decreases osteoclast activity, lengthens life
span of osteoblasts.
Parathyroid Glands

Secrete PTH: target tissues are
bone, kidneys and intestines.
Increases blood calcium
and phosphate levels
Stimulates osteoclasts
Promotes calcium
reabsorption by kidneys
and PO4 excretion
Increases synthesis of
vitamin D absorption
of Ca and PO4 by intestines
Regulation depends on
calcium levels.
Effects of Parathyroid Hormone
Adrenal Glands
Near superior poles of
kidneys;
retroperitoneal
Inner medulla; outer
cortex
Medulla: Secretes
epinephrine and
norepinephrine
Adrenal Glands
Cortex: three zones
from superficial to deep
Zona glomerulosa
Zona fasciculata
Zona reticularis
Hormones of Adrenal Cortex
Mineralocorticoids: Zona glomerulosa
Aldosterone - rate of sodium reabsorption by
kidneys sodium blood levels
Glucocorticoids: Zona fasciculata
Cortisol - fat and protein breakdown,
glucose synthesis, inflammatory response
Androgens: Zona reticularis
Weak androgens secreted then converted to
testosterone by peripheral tissues. Stimulate
pubic and axillary hair growth and sexual drive
in females

Adrenal Medulla
neurohormones: epinephrine and norepinephrine
Combine with adrenergic membrane-bound receptors
All function through G protein mechanisms
Secretion of hormones prepares body for physical activity
Effects are short-lived; hormones rapidly metabolized
Epinephrine
blood levels of glucose
Fat breakdown in adipose tissue
Causes dilation of blood vessels in skeletal muscles and
cardiac muscles.
Epinephrine and norepinephrine HR and force of
contraction; cause blood vessels to constrict in skin,
kidneys, GI tract, and other viscera
REGULATION OF ADRENAL MEDULLARY SECRETIONS
Stress and the Adrenal Gland
PANCREAS
retroperitoneal
Exocrine gland
Produces pancreatic
digestive juices
Endocrine gland
Consists of pancreatic islets
Composed of
Alpha cells-secrete
glucagon
Beta cells-secrete insulin
Delta cells-secrete
somatostatin

THE PANCREAS
Its major target is the liver, where it promotes:
Glycogenolysis the breakdown of glycogen to
glucose
Gluconeogenesis synthesis of glucose from lactic
acid and noncarbohydrates
Release of glucose to the blood from liver cells
Glucagon
Target tissuesliver, adipose tissue, muscle, and
satiety center of hypothalamus
Lowers blood glucose levels
Enhances transport of glucose into body cells
Counters metabolic
activity that would
enhance blood
glucose levels
Insulin


Regulation of Blood Glucose Levels
Results from hyposecretion or
hypoactivity of insulin
The three cardinal signs of DM
are:
Polyuria huge urine output
Polydipsia excessive thirst
Polyphagia excessive hunger
and food consumption
Hyperinsulinism excessive
insulin secretion, resulting in
hypoglycemia
Diabetes Mellitus (DM)
Diabetes Mellitus (DM)
Hormones of the Reproductive System
Male: Testes
Testosterone
Regulates production of
sperm cells and
development and
maintenance of male
reproductive organs and
secondary sex
characteristics
Inhibin
Inhibits FSH secretion

Hormones of the Reproductive System
Female: Ovaries
Estrogen and Progesterone
Uterine and mammary
gland development and
function, external genitalia
structure, secondary sex
characteristics, menstrual
cycle
Inhibin
Inhibits FSH secretion
Relaxin
Increases flexibility of
symphysis pubis


Pineal Body
In epithalamus; produces melatonin
Thymus Gland, GI Tract, Kidneys
Thymosin-development of the immune system.
GI tract- several hormones regulate digestion and
enzyme secretion
Kidneys secrete erythropoietin, which signals
the production of red blood cells
Adipose tissue releases leptin, which is involved
in the sensation of satiety, and stimulates
increased energy expenditure

Hormone-like Substances
Autocrines: chemical signals released by a cell
and the substance affects that same cell.
Chemical mediators of inflammation which are
modified fatty acids: eicosanoids such as
prostaglandins, thromboxanes, prostacyclins,
and leukotrienes
Paracrines: chemical signals released into
intercellular fluid and affecting nearby cells.
Endorphins and enkephalins modulate
sensation of pain
Several growth factors
REFERENCES
Seely, R, Stephens, T, Tate, P. Essentials of Anatomy
and Physiology. 6th ed. International Edition 2008.
Mc Graw Hill Publishing

Marieb, E., Hoehn, K. Essentials of Human Anatomy
and Physiology. 9th ed. Pearson Education Inc. 2011.