Dr. Adel Hussien

Assistant Prof. of Physiology

Physiology dept.-Faculty of

Medicine – Minia University

Endocrine

Introduction to the endocrine system

Learning objectives:

What is the endocrine system?

What is the hormone?

- Chemical nature of hormones

- Mechanism of action of hormones

Introduction to Endocrine System

Endocrine glands: glands that secrete hormones directly into blood

stream to affect target tissues & organs all over the body

(notice the difference from exocrine glands)

Pituitary gland is the master of endocrine glands

and pituitary itself is under control of hypothalamus

Major endocrine glands:

- Thyroid

- Parathyroid

- Suprarenal gland (cortex & medulla)

- Gonads (testes & ovaries)

- Pancreas (islets of Langerhans)

Connection between hypothalamus and pituitary

1- Hypothalamo-hypophyseal portal

circulation

Circulaton between the hypothalamus

& anterior pituitary..carry releasing or

inhibiting hormones from hypothalamus

to affect secretion of anterior pituitary

gland

e.g. TSH, ACTH, FSH &LH…

2- Hypothalamo-hypophyseal tract

Nerve fiber connection between the hypothalamus and posterior

pituitary.. ADH & oxytocin hormone formed in

hypothalamus..released & stored in the posterior pituitary gland

Hormones

These are chemical substances secreted by specific cells (endocrine

glands) directly into the blood to affect nearby or distant target cells

(i.e. chemical messengers)

Chemistry of hormones:

1- proteins & Polypeptides: pituitary, pancreatic, parathyroid &

hypothalamic hormones

2- Steroid hormones (derived from cholesterol): suprarenal cortex

hormones, sex hormones & vitamin D derivatives

3- Tyrosine derivatives (single amino acid): thyroid hormones &

catecholamines

Feedback control of hormone secretion

* According to the type

1- Negative feedback

2- Positive feedback

.

*According to distance of feedback

1- Long loop feedback

The hormone secreted by the endocrine

gland affects hypothalamus and anterior

pituitary gland

2- Short loop feedback

The hormone secreted by anterior pituitary

affects the hypothalamus

3- Ultra short loop feedback

The hormone secreted by the

hypothalamus return and affecting the

Hypothalamus again

(autocrine effect)

Ultra

short

loop

Hormone receptors:

Hormones act on target tissues through binding to their specific receptors

- On the cell membrane of tissues e.g. protein hormones

- In the cytoplasm e.g. steroid hormones

- In the nucleus e.g. Thyroid hormones

These receptors are specific to each hormone

There response is changed with various stimuli according to metabolic needs

Mechanisms of hormone action

Binding of hormones to their receptors…formation of hormone-receptor

complex…act by one of the following mechanisms

1- Genomic mechanism: transcription of DNA (genetic

material)…mRNA..synthesis of enzymes

2- Non genomic mechanism: No DNA transcription, but activation of a

cell membrane or cytoplasmic mechanism. Increase intracellular

second messenger like cAMP, cGMP, calcium

3- Combined genomic and non genomic mechanism

The pituitary gland (Hypophysis cerebri)

Learning objectives:

- Hormones secreted by the anterior pituitary gland

- Regulation of anterior pituitary hormones secretion

- Disorders of pituitary hormones secretion (GH)

The pituitary gland is functionally divided into

1- Anterior pituitary (anterior lobe, adenohypophysis)

2- Posterior pituitary (posterior lobe, neurohypophysis)

Hormones of anterior pituitary

The anterior pituitary produces and

secretes the following hormones:

1- GH Growth hormone ( from somatotropes)

Somatotrophic hormone, somatotropin

2- TSH Thyroid stimulating hormone (from

thyrotropes)

Thyrotrophic hormone, thyrotropin

3- FSH, LH (from gonadotropes)

Gonadotrophic hormones, gonadotropins

4- ACTH Adrenocorticotrophic hormone

(from corticotropes)

Corticotrophic hormone, corticotropin

5- Prl Prolactin (from mammotropes)

Mammotrophic hormone, mammotropin

Hypothalamic control of anterior pituitary:

The hypothalamus release the following

hormones (factors) into the hypothalamic

Hypophyseal portal circulation to control

anterior pituitary hormones secretion

1- GHRH Growth hormone releasing hormone

2- GHIH Growth hormone inhibiting hormone (somatostatin)

3- TRH Thyrotropin releasing hormone

4- GnRH Gonadotropin releasing hormones

5- CRH Corticotropin releasing hormone

6- PIH Prolactin inhibiting hormone

(Dopamine)

Growth Hormone (GH, Somatotropin)

It is a protein hormone about 191 amino acids secreted in pulsatile

pattern from

Physiological functions:

I- Effect on growth: GH increases protein synthesis, cell division and

proliferation…increase size and number of cells…growth of body

tissues

(1) Soft tissues: increase size of tissues and organs as heart, lung,

stomach..

(2) Skeleton:

A- Before puberty (before union of epiphysis with the shaft of long

bones GH stimulates

- Differentiation of chondrocytes into osteogenic cells..increase protein

deposition by these cells..deposition of new bones

- Chondrocytes…local production of insulin like growth factor1 (IGF1)

..increased growth of epiphyseal cartilage and conversion into new

bone..elongation of the shaft..increase linear growth of bone

- Osteoblasts in bone periosteum..deposition of new bone on the bone

surface…increase thickness of bones

B- After puberty (after union of epiphysis)

GH increase only the thickness of bones No increase in linear growth

The effect of growth hormone on growth is indirect through

somatomedins

Somatomedins:

- Polypeptides secreted by liver and other tissues as cartilage

- Their effects on growth similar to those of insulin (insulin like actions)

- The most important among 4 types is somatomedin C (IGF1)

produced by the liver and chondrocytes

II- Effects on metabolism

(1) Protein metabolism: anabolic (increase body protein) through

- Increase amino acids uptake & transport into the cells

- Increase transcription of DNA, formation of mRNA, and translation of

RNA…increase protein synthesis

- Decrease protein catabolism.. Inhances uses fatty acids for energy

production and spare protein

(2) Carbohydrate metabolism: Hperglycaemic, diabetogenic effect

- Increase glucose production by the liver & increase gylcogenesis &

glycogen deposition

- Decrease glucose uptake by cells (inhibition of glucokinase in skeletal

muscles and fat cells)

- Decrease glucose utilization by cells (decrease glycolysis & glucose

oxidation)

.

(3) Fat metabolism: lipolytic and ketogenic effect

- GH stimulates lipolysis (destruction of fat) & mobilization of free

fatty acids (FFA) from adipose tissue to blood…hyperlipidaemia

Regulation of GH secretion

(1) Hypothalamic control: through

- Growth hormone releasing

hormone (GHRH)

- Growth hormone inhibiting

hormone (GHIH, Somatostatin)

(2) –ve feedback control:

- Long loop feedback:

IGF1 at pituitary &

hypothalamic level

- Short loop feedback:

between GH & GHRH

- Ultra short loop feedback:

GHRH on itself

Factors affecting GH secretion

A- Factors increasing GH secretion:

1- Decrease blood glucose & FFA level

2- Fasting & starvation

3- Protein meal & I.V. injection of amino acids

4- Exercise

5- Start of deep sleep

6- Sex hormones, estrogens & androgens

B- Factors decreasing GH secretion:

1- Increase blood glucose & FFA level

2- Obesity

3- Aging

4- Some hormones, cortisol, somatostatin & exogenous GH

.

Disturbances of GH function

The disturbance may be

1- GH hypofunction : due to decreased GH secretion

2- GH hyperfunction: due to increased GH secretion

1- Effects of GH hypofunction

A- Pituitary dwarfism: Occurs due to the following causes

1- Decrease GH secretion from anterior pituitary

2- Decrease GHRH secretion from hypothalamus

3- Decrease IGF1 secretion from liver and chondrocytes

Levi-Lorain dwarf: GH secretion is normal or even high but there is hereditary inability to form somatomedin C

4- Laron dwarfism: GH receptors defect that leads to insensitivity to GH

Characters:

1- Physical growth: arrested growth of the child

- Short stature (100-120cm)

- Proportionate decrease in size of trunk and extremities (span=hight & vertex to symphysis= symphysis to heel)

2- Sexual & mental development: normal

Some of them are intelligent but may be psychologically unstable

B- Pituitary infantilism: Pituitary dwarfism+hypogonadism due to additional decrease in gonadotrphic hormones

2- Effects of hyperfunction

A- Gigantism (Giantism)

Cause: acidophilic adenoma..increase GH secretion before union of

epiphysis of long bones (Before puberty, prepubertal)

Characters: symmetrical growth of soft tissues and skeleton

1. The patient becomes very tall, may reach 3 meters in height

(span=height & vertex to symphysis= symphysis to heel)

2- Hyperglycaemia, glucosuria & diabetes mellitus (DM in 10% of

cases)

3- Hypogonadism due to pressure on basophil cells secreting GnHs

4- Ends in panhypopituitarism and death due to destruction of all cells of

the pituitary

B- Acromegaly:

Cause: increase GH secretion after union of epiphysis of long bones

(after puberty, postpubertal)

Characters:

1. Skeletal growth: No linear growth of long bones but all bones of the

body (flat & long) increase in thickness .

- Hands and feet become large & broad

- Skull, box shaped with prominent cheeks, nasal bones,superciliary

ridges

- Mandible, protruded lower jaw (prognathism) & widely separated

teeth

- Kyphosis (spine bends) due to over growth of vertebrae

2. Soft tissue growth

- Overgrowth of skin & soft tissues of the face…wrinkling of the scalp

& forehead ( bulldog facies)

- Overgrowth of muscle & viscera, patient very strong for few years

then becomes weak

3. Hyperglycaemia & glucosuria & 2ry diabetes may occur later in the

disease due to exhaustion of beta cells of pancreas

Hormones of posterior pituitary

1- Antidiuretic hormone (ADH-Vasopressin)

Functions:

1- On the kidney

ADH increases water reabsorption by distal convoluted and collecting

tubules of the kidney…..decrease urine volume

2- On smooth muscle in blood vessels

In excess doses it leads to generalized vasoconstriction….increases

blood pressure

Control of ADH secretion

1- Osmotic pressure of plasma

Increase osmotic pressure of plasma (as in dehydration)…increase

ADH secretion

Decrease osmotic pressure of plasma (as in overehydration)…dncrease

ADH secretion

2- Volume of extracellular fluid (ECF)

Marked decrease in blood volume (as in hemorrhage)…increase ADH

secretion while increased blood volume has the opposite effect

3- Nervous factors

Stressful stimuli….increase ADH secretion

Cold exposure…..decrease ADH secretion

Dirorders of ADH secretion

Diabetes insipidus (DI)

Causes:

- Decrease ADH secretion due to lesion in the hypothalamus

(neurogenic DI)

- Nephrogenic DI is due to abnomality in ADH receptors of the kidney

(ADH secretion is normal)

Manifestations of DI:

- Polyuria: increased urine formation (may reach 20liters/day)

- Polydypsia: excessive water intake

- Loss of water soluble vitamins in urine

- Marked increase in basal metabolic rate (BMR)

Neurogenic DI responds to exogenous ADH administration but

nephrogenic DI does not.

2- Oxytocin

Functions:

1- Milk ejection

2- Contraction of uterus

3- Slight vasoconstrictor and antidiuretic effect

Control of secretion:

Oxytocin increases by reflex action

- During Suckling

- During Labor