“The endocrine system”

By

Dr. Mary A. Youssef

________________________________

Cairo University

2012

Two main control systems

1. The nervous system

2. The endocrine system

Rapid control system

Slow control system

Exocrine glands Endocrine glands

Have ducts ductless

Secrete their products to the outer surface or the

lumen of GIT

Secrete their products (hormones) into the

blood

Can not Can reach distant tissue

2. The endocrine system

hypothalamus

Gland

Hormone

(Sender)

(signal)

blood

receptor (receiver & transducer)

Hormone

Target cell

Small amount

Rate of secretion

Superadded rhythms

Effector

Opposing effects

Classification of hormones

1. According to their chemical nature

olypeptide H.protein and P. 1 Hypothalamic, pituitary, pancreatic & parathyroid H.

. Steroid H.2

Adrenocortical and gonadal H.

. Hormones derived from a.a.3

Thyroid h. & adrenal medullary h.

cortex

2. According to their origin

Hypophysiotropic hormones

1. Releasing H.

GHRH

Thyrotropin (TSH) RH (TRH)

Corticotropin RH

Gonadotropin RH

2. Inhibiting H.

Somatostatin (SS)

Prolactin inhibiting H.

Hypothalamus

Hypothalamus

Anterior pituitary

posterior pituitary

prolactin H. Thyrotropin

TSH

Thyroid G. T3&T4

Growth H. Corticotropin

ACTH

steroids

FSH & LH (gonadotropins)

gonads

Sex H.

Anti-diuretic H.

(ADH)

Oxytocin

GHIH (SS) GHRH

PIH

TRH

CRH

GnRH

Mechanisms of hormone action

What is meant by a target cell?

GH

What are the target cells of GHRH?

a. cells of the Hypothalamus

b. Anterior pituitary cells

c. Posterior pituitary cells

d. Bone cells

I. Mechanism of action of protein & polypeptide hormones:

The hormone (1ry messenger) binds to a cell membrane receptor of target cell

formation of a 2nd messenger inside the cell

changing the activity of certain enzymes

- cAMP

- Calcium-calmodulin

- DAG & IP3

Hormone

(1ry messenger)

Receptor

1. cAMP system

Change certain

enzymes activity

(2ry messenger)

2. Calcium-calmodulin system

Change certain enzymes activity

Hormone

(1ry messenger)

(2ry messenger)

calmodulin

3. Membrane phospholipid system

DAG

IP3

Hormone

(1ry messenger)

Change certain enzymes activity

(2ry messenger)

II. Mechanism of action of Steroid H.

Receptor

Increase or a decrease in the synthesis of a certain protein

III. Mechanism of action of Thyroid H.

T T

T T

T

T

Receptor

Increase in the synthesis of certain proteins in almost all cells

H. derived from a.a.

Steroid H. Protein or

polypeptide H.

Nuclear R. Cytoplasmic R. Cell membrane

R.

_ _

2ry messenger - cAMP -Ca-calmodulin

-DAG & IP3

Synthesis of new proteins

Synthesis of new proteins

Change the activity of

already present enzymes

Thyroid & adrenal

medullary h.

Adrenocortical & Gonadal h.

Hypothalamic, pituitary,

parathyroid, pancreatic

Regulation of hormone secretion

Target gland

Hypothalamus

Ant. Pituitary G.

Target gland hormone

Substrate Mineral

Mineral-hormone feedback

Substrate-hormone feedback

Hormone-hormone feedback

The pituitary gland (hypophysis)

Hypothalamo- hypophyseal portal vessels

GHIH (ss)

GHRH

PIH

TRH

CRH

GnRH

Adenohypophysis

Hypothalamic neurons

Hypothalamo-hypophyseal tract

Anterior pituitary gland hormones

The anterior pituitary produces & secretes its own hormones

Its Hormones are given the extension; tropic, tropin or trophic

It is the master for the majority of the endocrine glands

Hypothalamus

Anterior pituitary

posterior pituitary

prolactin H. Thyrotropin

TSH

Thyroid G. T3&T4

Growth H. Corticotropin

ACTH

steroids

FSH & LH (gonadotropins)

gonads

Sex H.

Anti-diuretic H.

(ADH)

Oxytocin

Anterior pituitary gland hormones

Which of these is not produced by

the anterior pituitary?

►ACTH

►follicle-stimulating hormone (FSH)

►Somatostatin (ss)

►Somatotropic H.

Growth hormone

(somatotropic hormone)

It is a protein hormone that stimulates growth

1. On bone growth

Actions of growth hormone

GH

somatomedin

2. On protein metabolism

It is an anabolic hormone

mRNA

a.a. a.a.

1. Rate of DNA transcription

2. a.a. transport into the cell

3. On carbohydrate metabolism

It increases blood glucose level (diabetogenic action)

glucose Glucose 6-PO4

Glycogen

Glycogen synthase

phosphorylase

Insulin R.

Glucose transporter pyruvate

2 X Glycolysis

1

4. On lipid metabolism

Fat (T.G.)

GH Lipolysis

FA Glycerol

FFA

Factors affecting GH secretion

GH secretion is increased by GHRH Low blood glucose and FFA Protein meal Emotional stress Deep sleep

GH secretion is Decreased by somatostatin High blood glucose and FFA treatment with corticosteroids

Disorders of GH secretion

A. Growth hormone deficiency (dwarfism)

Decrease in the size of the trunk & extremities

Normal mental & sexual development

GH Gonadotropins

Pituitary infantilism

Failure of:

Physical development

Sexual development

B. Growth hormone Excess Before closure of epiphyses Gigantism

taller than normal

After closure of epiphysis Acromegaly

Main features of acromegaly

No linear growth of bones

1.Bones of hands and feet

2.Bones of the face

3.Mandible

4.The spine

5.Diabetes

Excess Deficiency Actions Hormone

:Gigantism

Before closure of epiphysis

Acromegaly

After closure of epiphysis

Pituitary dwarfism:

Only failure of physical develop.

Pituitary infantilism:

Failure of physical &

sexual develop.

On bone linear growth (via

somatomedin)

On protein Anabolic

On CHO

Diabetogenic

On lipid lipolysis

Growth H.

(Ant. (Pituitary

Growth hormone

A. directly stimulates growth of cartilage and bone.

B. enhances protein breakdown in nonvital muscles.

C. levels are subnormal in Gigantism.

D. promotes lipolysis in adipose tissue.

Posterior pituitary gland hormones

Antidiuretic hormone (ADH)

(Vasopressin)

It is a protein hormone

Formed in supraoptic n. of the hypothalamus and secreted from the posterior pituitary

Actions of ADH (vasopressin)

1. On Kidney

Anti-diuresis (retention of water)

2. On blood vessels

Pressor effect

3. On smooth muscles

Contraction of the smooth muscles

Antidiuretic H.

Summary of the actions of ADH

Antidiuretic hormone

Blood volume Vascular resistance

Arterial blood pressure

Regulation of ADH secretion

ADH secretion is increased by osmotic pressure of ECF blood volume (e.g. Hge) Stress Drugs (e.g. morphine & nicotine)

osmoreceptors

H2o

Na+ +

-

Baroreceptors & low pressure R

Hypovolaemia

Disorders of ADH secretion

ADH deficiency

Diabetes insipidus

1. Polyuria

2. Polydipsia

3. Loss of water

soluble vitamins

Oxytocin

It is a protein hormone

Formed in paraventricular n. of the hypothalamus and secreted from the posterior pituitary

Actions of Oxytocin

1.Uterine contraction during delivery

2.Milk ejection action during suckling

3.Mild antidiuretic action

The Thyroid gland

Histology

1.Follicles

Lined with a single layer of epithelial cells

Its centre is filled with colloid

2. Parafollicular cells

Hormones secreted from the thyroid gland

From parafollicular cells

From thyroid follicle cells

Thyrocalcitonin (calcitonin)

Thyroid Hormones

T3 (tri-iodothyronine)

T4 (tetra-iodothyronine, thyroxine)

It affects Ca homeostasis

It affects body metabolism

Actions of Thyroid hormones

T T

T T

T

T

Synthesis of new protein

Receptor

mRNA

Proteins for growth &

maturation

Enzymes & transport

ptns

of oNmitochondria

O2

substrate

GIT

Metabolism Calorigenic

effect

2

3

4

5 Respiration 1

6 CVS

blood glucose

blood FFA (lipolysis) CNS 7

Physical

mental

Sexual O2 consumption Metabolic rate

Regulation of thyroid hormones

Thyroid h. secretion is regulated by :

1. TRH

2. TSH

3. Feedback

Mechanism

4. Cold

5. Stress

Ant. pituitary

Hypothalamus

Thyroid

++

--

--

Cold & emotional

stress

+

Iodine deficiency

++

Disorders of thyroid hormone secretion

A. Hypothyroidism

1. BMR & calorigenesis

2.Generalized decrease in activity of all body systems

3.Myxoedematous tissue CVS: Heart rate & Cardiac output

GIT: intestinal motility (constipation)

CNS: slow mentation & sluggish reactions, S

In adults Myxoedema

Since birth Cretinism

Delayed physically: Dwarf, teeth erupt later than normal

Delayed mentally

Delayed sexually

Special features:

Depressed nasal bridge

Wide nostrils

Protruding tongue

Protuberant abdomen

B. Hyperthyroidism (thyrotoxicosis)

One of its types is Grave’s disease (exophthalmic

goitre)

Autoimmune disease

TSH-R(stim) Ab

TSH-R (stim) Ab

Characters of hyperthyroidism

1. BMR & calorigenesis

2.Generalized increase in activity of all body systems

3.Loss of weight in spite of increased food intake

CVS: Heart rate & Cardiac output

GIT: intestinal motility (diarrhea)

CNS: tremors, irritability, insomnia

Calcium homeostasis

The adult human body contains 1 Kg of calcium

Functions of calcium:

1.Mineralization of bones & teeth

2.Blood clotting

3.Neuromuscular excitability

4.Muscle contraction & relaxation

5.Release of neurotransmitters

6.Hormonal secretion & act as a 2ry messenger

8

Diet 1g

Extracellular fluid 1g

175 mg

1 Kg

1% exchangable in bone fluid

99% stable in mineralized

bone

10 g filtered/day

175 mg

Plasma calcium:

Its concentration is about 10mg/dl 1. Ionized 50%

2. Bound to protein 40%

3. Complex & diffusible form 10%

Solubility product:

[Ca2+] x [PO43-] = constant

Bone

Bone tissue is formed of:

1. Organic matrix (formed mainly of collagen)

2. Crystalline salts (mainly hydroxyapatite crystals & calcium phosphate)

3. Bone cells

A. Osteoblast

B. Osteocyte

C. Osteoclasts

Ca hydroxide

Ca phosphate

hydroxyapatite

Bone matrix proteins

Alkaline phosphatase

Bone forming

cells

Secrete H+ that dissolve hydroxyapatite

Acid protease that dissolve collagen

Bone eating cells

Secrete

Phosphate ester phosphate

Ca phosphate

Outer surface of the bone

Osteoblasts

Osteocytes

10 mg/dl Ca++

Ca bound to ptn Complex form

Bone fluids

Hydroxy-apatite crystals

Hormonal control of plasma Ca level

3 hormones play a role in the control of plasma Ca level

1. Parathormone hormone (PTH) : Parathyroid glandSource

:Actions

1. On bones

A.Rapid phase

B.Slow Phase

2. On kidney

3. On GIT

PTH

Ca++

Ca++

Ca++

Ca++

Ca++

Hydroxyapatite crystals

Ca++

2. On kidney

PCT

DCT Ca++

PO4

+

-

Ca++ reabsorption

Phosphate reabsorption

Ca++ absorption

ECF Ca++

ECF PO43-

3. Vitamin D2

Skin Source:

25-hydroxy-cholecalcife

rol

1, 25-dihydroxy cholecalciferol

ECF Ca++

ECF PO43-

. Calcitonin3

: parafollicular cellsSource

:Actions

1. On Bone (inhibits activity of osteoclats)

2. On kidney

ECF Ca++

ECF PO43-

Ca++

PO4

-

-

Tetany It is a state of increased neuromuscular excitability due to decreased ionized calcium

Causes

Types:

Latent tetany: when the total plasma Ca is between 9 and 7 mg/dl. Its manifestations do not appear during rest

Manifest tetany: when the total plasma Ca

drops below 7mg%. The patient is presented by spasmodic contractions

Hypoparathyroidism Vitamin D deficiency Renal disease Akalemia

The adrenal glands

Each adrenal gland consists of two endocrine organs

1. Adrenal cortex

Secretes steroid hormones

2. Adrenal medulla

Secretes catecholamines

cortex

C

ort

ex

Medulla

Zona glomerulosa

Zona Fasciculata

Zona Reticularis

Mineralocorticoids

Glucocorticoids

Sex Hormones

Aldosterone

cortisol

Androgens & estrogen

A. Glucocorticoids

Cortisol = 95% of total glucocorticoid activity.

Actions of cortisol depends on its plasma level:

1. Permissive Actions

2. Physiological Actions

3. Pharmacological Actions

its presence even at small amounts permits certain processes to occur

Effects of the normally present hormone levels in plasma

Effects of the high levels of hormone in plasma

It means that cortisol does not initiate the changes, but its presence even at small amounts permits certain processes

1. Permissive Actions

Glucagon & catecholamines

Glycogenolysis

Catecholamines Arteriolar V.C. response &

bronchodilatation

2. physiological Actions

I. Effect on metabolism

Glucose

Gluconeogenesis

glycogen

glucose Glucose 6-PO4

Glycogen Glycogen synthase

phosphorylase

pyruvate

3 Glycolysis

2

Blood glucose

protein Fat (T.G.)

Lipolysis

FA Glycerol

Blood FFA

1

a.a.

II. Effect on CNS

Required for normal EEG pattern

III. Weak mineralocorticoid effect

IV. Anti-stress effect

I. Effect on metabolism

V.C. catecholamines

Permissive action

Blood glucose Plasma a.a. Plasma FFA

3. pharmacological Actions

I. Anti-allergic effect

II. Anti-inflammatory effect

Mast cell

Local redness

Local heat

Local swelling

V.D.

Capillary permeability

Phospholipids

PGs

Local pain

Loss of function

Destruction of cells

Lysosomes

White blood cells Eosinophils

Basophils

Phagocytic cells

Walling off of infections

Fibroblasts

1

2

3

4

5

Control of glucocorticoid secretion

1

2

3

4 5

hypothalamus

B. Mineralocorticoids

Actions:

DCT

Collecting duct

Na+

K+

Aldosterone actions H2O

ECFV

Cushing’s syndrome 1.cause: Hypersecretion of cortisol + excess androgen

. Features2

I. Excess cortisol

1.CHO metabolism (DM)

2.Excess protein catabolism

3.Disturbed fat deposition

II. Mineralocorticoid effect

III. Excess Androgens

Moon face

Buffalo hump

Purple striae

Disorders of adrenocortical hormones

Addison’s syndrome

1.cause:

Hyposecretion of adrenocortical hormones

. Features2

I. Mineralocorticoid deficiency

1. Hypotension

2. Polyuria & polydipsia

3. Hyperkalemia

B. Mineraloco

rticoids

Actions:

Na+

K+

Aldosterone actions

H2O

ECFV

II. Glucocorticoid deficiency

Depression of many metabolic functions

hypoglycemia

1. Metabolism

- CHO metabolism

Decreased resistance to stress 3. During stress

ACTH skin pigmentation 4. ACTH

Loss of appetite weight loss 2. Appetite

Control of glucocorticoid secretion

hypothalamus

1

The Pancreas

Actions of insulin I. On CHO metabolism:

glucose Glucose 6-PO4

Glycogen

Glycogen synthase

phosphorylase

Insulin R.

Glucose transporter pyruvate

Glycolysis

In skeletal m., cardiac m. & adipose tissue

Glucose

Glucose

Glucose 6 P

+

Glycogen

Glycogenesis +

Glycogenolysis -

gluconeogensis -

1. Indirectly facilitates glucose entery

2. Promotes glycogenesis

3. Inhibits glycogenolysis

4. Inhibits gluconeogensis

In the liver

II. On lipid metabolism: lipogenesis

III. On protein metabolism: (Anabolic)

mRNA

a.a. a.a.

1. Rate of DNA transcription

2. a.a. transport into the cell

IV. On Growth

Actions of Glucagon

Glucagon Insulin

glycogenolysis

gluconeogenesis

glycogenolysis

gluconeogenesis

On CHO metabolism

Lipolysis Lipogenesis On lipid metabolism

Catabolic Anabolic On protein metabolism

hypoglycemia hyperglycemia Stimulus

Diabetes mellitus

Signs & symptoms

urine Blood Response Organ/tissue

Polyuria

dehydration

glucosuria

Hyperglycemia

Decreased glucose uptake

Polydipsia Osmotic diuresis

Hyperglycemia

Glycogenolysis

Gluconeo-genesis

Weight loss

Polyphagia

(Hyperphagia)

Protein catabolism

Glucose Homeostasis

The importance to maintain a normal blood glucose concentration

Body response to ingestion of a meal (high glucose)

100

120

140

1h 2h 3h 4h

Insulin returns blood glucose level back to control level

Mechanisms controlling blood glucose concentration

1. Glucostatic function of the liver

Glycogenesis (after meals) Glycogenolysis (between meals) Gluconeogenesis (during fasting)

2. Hormonal Mechanism

Both insulin & glucagon function as important feedback control systems to maintain a normal blood glucose level

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