Introduction : Endocrine system formed of all endocrine glands of body. Though different endocrine glands are different in embryonic origin and are isolated from one another but these interact with one another so collectively form an endocrine system. Endocrine system along with nervous system, controls and coordinates the body functions and maintains a homeostais. So both are collectively form neuro-endocrine system. The study of these two systems is called neuro-endocrinology.

The nervous system achieves functional co-ordination and integration for quick responses of body, like a high- speed service. Contrarily, the endocrine system achieves co-ordination and integration for slow responses of body, like a low speed service.

Glands of body : A cell, a tissue or an organ which secretes certain useful chemical compounds is called a gland. Animals have three types of glands.

1. Exocrine gland (Gr., ex = out + krinein = to secrete) : These glands have ducts for discharging their secretions. Therefore, they called duct glands. ex – Liver, Sweat gland, Sebaceous gland, Gastric glands and some intestinal glands.
2. Endocrine glands ( Gr., endo = within + krinein = to secrete) : These glands lack ducts and pass secretions into the surrounding blood directly. Therefore they called ductless glands. ex – Thyroid, parathyroid, adrenal, pituitary, pineal body and thymus.
3. Heterocrine glands : These glands consist of both exocrine and endocrine tissue. The exocrine discharge its secretion by a duct and the endocrine tissue discharge its secretion into the blood. Pancreas and gonads are heterocrine glands. These are also called mixed glands.

  Hormones and their mechanism                                                                                                                      

Hormones are informational molecules secreted by the endocrine cells in one part of the body and carried by blood to another part where they stimulate or inhibit specific physiological process. In other words the hormones are chemical messengers or informational molecules that regulate the biological processes and metabolism. Hormones organs called target organs. Targate cells have receptor proteins for specific hormone.

Discovery : First hormone discovered was secretin. It was discovered by two English physiologists : William M Bayliss and Ernest H. Starling in 1903.

Nomenclature : Term hormone was coined by starling (1905) from Greek work Hormaein means to excite.

It is a mishomer because a number of hormones are known to have inhibitory effect (e.g. Somatostatin)

(i)Properties of hormones

1. These are secreted by endocrine gland (biogenic in origin).
2. Their secretions is released directly into blood (except local hormones e.g. gastrin).
3. These are carried to distantly located specific organs, called target organ.
4. These have specific physiological action (excitatory or inhibatory). These co-ordinate different physical, mental and metabolic activities and maintain homeostasis.
5. The hormones have low molecular weight e.g. ADH has a molecular weight of 600–2000 daltons.
6. These act in very low concentration e.g. around10^–10 molar.
7. Hormones are non antigenic.

8. These are mostly short-lived. So have a no camulative effect.
9. Some hormones are quick acting e.g. adrenalin, while some acting slowly e.g. ostrogen of ovary.
10. Some hormones secreted in inactive form called Prohormone e.g. Pro-insulin.
11. Hormones are specific. They are carriers of specific information to their specific target organ. Only those target cell respond to a particular hormone for which they have receptors.

(ii)Classification of hormones

1. On the basis of chemical nature : On the basis of chemical composition hormones are classified into three categories.

1. Amine hormones : These are derived form tyrosine amino acid and have amino (- NH2 )

Thyroxine, Epinephrine, Nor-epinephrine.

group e.g.

2. Steroids : These are fat soluble and have sterol group. These are derived from cholesterol e.g. hormones of adrenal cortex (cartisol, cartisone, carticasterone, aldasterone) testes (testosterone etc.) and ovaries (estrone, estradiol, progesterone etc.)
3. Proteinous and peptide hormones : These are formed of 3 – 200 amino acids interlinked by peptide bonds and are water soluble e.g.

1. Proteinous hormones like STH, TSH, FSH, LH etc. Out of these FSH and LH are glycoproteins.
2. Long peptide hormones like insulin and glucagon, ACTH, Paratharmone.
3. Short peptide hormones like oxytocin, ADH, MSH. These hormones formed of a few amino acids.

(b)On the basis of mode of action

1. Quick acting hormones : These hormones initiate immediate response from their target cells. There receptor is always located on the outer surface of plasma membrane of target cell because these are large sized. Hormone receptor complex activates a membrane enzyme adenyl cyclase which hydrolise ATP into cyclic AMP. Which acts as secondary messenger, c-AMP activates an inactive enzyme system by cassade effect. So their mode of action is called second messenger hypothesis. e.g. These includes proteinous, peptide and amine hormones.
2. Short acting hormones : These hormones intiate response after some time. These are small sized so are diffusable through the plasma membrane of their target cell. These bind their proteinous receptor present in the cytosol. These always operate through de-novo synthesis of m-RNA by activation of certain genes. So their mechanism of action is called m-RNA hypothesis. e.g. These include steroid hormones of testes, ovary and adrenal cortex.

3. Differences between hormone and enzymes : Though both hormones and enzymes regulate the body functions, but they have following differences.

4. Difference between hormone and vitamin : Though both hormones and vitamins are similar in being organic (compounds; required in micro-amount and regulate the metabolic functions, but two also differ in a number of characters.

5. Differences between nervous and hormonal informations : Both hormonal and nervous system control and coordinate the body functions and work in co-ordination to maintain a steady state condition, called homeostasis. But two types of controls differ in some important characters.

6. Release of hormones : Hormones are released from endocrine glands by three types of stimuli.

1. Specific metabolic : The presence of a specific metabolite in the blood elicits the hormone to deal with it. For instance excess of glucose in the blood causes the release of insulin from the pancreas.
2. Other hormone : The presence of a specific hormone in the blood induces the release of another hormone. For example TSH stimulate thyroid gland to release thyroxine hormone.
3. Neuronal impulse : Neurons of autonomic system stimulate hormone release from some glands. For example adrenaline and nor-adrenaline are released from adrenal medulla on the arrival of nerve impulses during anxiety, stress and danger.

7. Mechanism of hormone action : The hormones act in two ways –

On cell surface and within a cell.

1. On cell surface : The molecules of hormones that are amino acid derivatives, peptides or proteins are large and insoluble in lipid, and can not enter the target cell. Therefore they act at the cell surface. They bind to specific receptor molecules located on the surface of cell membrane. The hormone receptor complex may acts in one of the two ways –
   1. Formation of cAMP : Mechanism of formation of cAMP was discovered by E.W. Sutherland in 1950. The hormone receptor complex causes the release of an enzyme adenyl cyclase. From the receptor site. This enzyme hydrolise the ATP into c-AMP. The c-AMP activates the existing enzyme system of the cell. This accelerates the metabolic reactions in cell. The hormone is called first messenger and the c-AMP is termed the second messenger. e.g. Adrenaline causes the secretion of glucose from the liver cell from this mechanism.

HORMONE (FIRST MESSENGER)

Fig. – Mechanism of Hormone action on cell surface

STEROID HORMONES

THYROID HORMONES

Fig. – Mechanism of cell surface within a cell

2. Change in membrane permeability : The receptor proteins of some hormones are large transmembrane intrinsic protein acting as ion channels for facilitated diffusion of Na⁺, K⁺, Ca²⁺ etc. On binding with specific hormone these receptor proteins undergo conformational changes, so that the membrane permeability for ions is altered, resulting into important changes in metabolism.

For example insulin promotes the entry of glucose from blood into the muscles cells by increasing the permeability of sarcolemma to glucose.

2. Within a cell : The steroid hormones act within the cell. Their small, lipid soluble molecules pass through the cell membrane and bind to specific receptor molecules present in the cytoplasm. The receptor molecules carry them into the nucleus. Here, the receptor hormone complex binds to a specific receptor site on the chromosome and activates certain genes that were previously repressed. The activated gene transcribe m-RNA which directs the synthesis of enzyme (protein molecule) in the cytoplasm. The enzyme molecule promote the metabolic reactions in the cell.

8. Feedback control of hormone secretion : The secretion of hormones is depends on age, daily routine, health of body. Physiological conditions of body etc. Besides the above factors hormone secretion is also depends on its own amount circulating in the blood. Decrease and increase in the circulating amount of a hormone

has a directly inverse effect on the secretion of hormone. This is known as the "pull and push" or "feed-back control" mechanism of hormonal secretion.

Several types of feedback mechanisms are found in the body. Most of these are of negative feedback, but some are of positive feedback. Some

HYPOTHALAMUS

negative feedback mechanisms are direct, while others are indirect.

(a)Negative feedback control

(1) Direct feedback control : Thyroid stimulating hormone (T.S.H.) stimulates the thyroid gland to secrete thyroxine hhormone. A high amount of thyroxine in the blood exerts an inhibitory effect on pituitory to secrete less T.S.H.. This eventually results a decrease in thyroxine. This is called "Direct feedback control".

Thyroxine hormone : A high amount of thyroxine in the blood exerts an inhibitory effect correction. This eventually results a decrease in thyroxine. This is call "direct feedback control".

2. Positive feedback control : Oxytocin released by posterior pituitary gland stimulate contraction of uterus during child birth. As the

HIGH BLOOD LEVEL OF THYROXINE

LOW TRH

ANTERIOR PITUITARY

LOW TSH

HIGH TRH

HIGH TSH

LOW BLOOD LEVEL OF THYROXINE

contraction of uterus progresses, more and more of oxytocin is released. Thigh is called positive feed back control.

1. Origin of different endocrine glands

Fig. – Feed back control of hormone secretion

(2)Functions of some important hormones

• MSH controls skin colour.
• Pituitary controls other endocrine glands.
• Thymosine secreted by the thymus gland provides immunity to the infants.
• Thyroid is the largest gland. Its hormone thyroxine controls oxidative metabolism.
• Normally, family planning pills consists of estrogen and progesterone.
• The Leydig cells secrete testosterone.
• Steroid sex hormones are secreted by the gondas. The hormones control the process of reproduction and secondary sexual characters.
• Adrenal gland is found attached to the kidney as cap. This gland secretes adrenalin and non-adrenalin hormones.
• Oxytocin controls parturition.
• Prolactin controls growth is mammary glands and secretion of milk in woman.
• FSH controls spermatogenesis.
• LH controls secretion of androgen from the Leydig cells in man and helps in the release of ovum from the ovary in woman.

(3)Number of hormones secreted by different endocrine glands

4. Discovery & Terms

• Term 'endocrine' was first used by Bernard.
• Thomas Addison is called as father of endocrinology.
• Walter canon stated that the hormones maintain homeostasis in the body.
• Von Euler coined the term 'prostaglandin'
• Kendall for the first time prepared the crystals of thyroxine.
• Harrington and Barger studied the molecular structure of thyroxine.
• Term 'thyroxine' was coned by Whartson.
• Sutherland discovered cAMP.
• Parathormone was first isolated by Collip.
• Potts discovered the structure of PTH.
• Axelord studied the structure of epinephrin and nor-epinephrin.
• Endocrine structures of the pancreas were discovered by langerhans.
• Structure of insulin was studied by Sanger. He was given Nobel prize in 1958. He was rewarded Nobel prize in 1980 for gene structure.
• Human insulin was synthesized by Tsan.
• Glucagon was discovered by Kimball and Murlin.
• Term ' Secretin' was coined by Beylis and Starling.
• Adrenalin gland was discovered by Eustachian.

 Pituitary Gland (Hypophysis)                                                                                                                            

Pituitory is known as hypophysis cerebri, its name pituitary was given by vesalius. Muller,s gland of amphioxus and subneural gland of hardmania is homologous to pituitary of vertebrates. Weight to pituitary is 0.5 gm. Removal of pituitary is knows as hypophysectomy.

1. Position and origin : Pituitary gland is the smallest (about 1 to 1½ cm in diameter) endocrine gland of the body. It is pea-shaped, ovoid, radish brown gland situated at the base of the brain in a cavity, the sell turcisa of sphenoid bone. It is connected by a short stalk called Infundibulum, to the ventral wall (Hypothalamus) of diencephalon. That is why it is also called hypophysis cerebri. It weight about 0.5 to 1 gm. It controls most of the endocrine glands. Hence, it is also called leader of endocrine orchestra or master gland. Pituitary gland is closely related with hypothalamus. Hence, it is also called hypothalamo-hypophyseal gland, pituitary is ectodermal in origin.

Parts and component

1. Adenohypophysis

1. Pars distalis
2. Pars tuberalis            Anterior lobe
3. Pars intermedia

(2)Neurohypophysis

1. Pars nervosa

HYPOTHALAMUS

ANTERIOR PITUITARY

POSTERIOR PITUITARY

2. Infundibulum

Posterior lobe

Fig. – Location of pituitary gland

2. Structure of pituitary gland : Pituitary gland is comprised of two main lobes – Adenohypophysis and Neurohypophysis. Adenohypophysis is arises as hypophysial or Rathke's pouch from dorsal wall of embyronic stomodeum. It is the anterior lobe of pituitary. The neurohypophysis (Pars nervosa or Posterior lobe) form as an outgrowth from the infundibulum of the floor of hypothalamus.

The anterior lobe includes three lobes – Pars tuberalis, Pars distalis and pars intermedia. The posterior lobe includes pars nervosa and infundibulum. The pars nervosa has the axons of the neurosecretory cells found in the hypothalamus. The axons form end knows which are called as Herring bodies. There are special pituicytes in

between the Herring bodies which are called neuroglial cells.

HYPOTHALAMUS

PARS       HYPOTHALAMUS TUBERALIS

3RD VENTRICLE

MEDIAN EMINENCE

MAMMILARY BODY

TUBER CINEREUM

MEDIAN EMINENCE

INFUNDIBULAR STEM

PARS NERVOSA

CLEFT

PARS TUBERALIS

PARS INTERMEDIA

PARS DISTALIS

INFUNDIBULAR STALK

PARS INTERMEDIA

PARS NERVOSA

POSTERIOR LOBE

ANTERIOR LOBE

PARS DISTALIS

Fig. – Structure of pituitary gland

In pituitary following types of cells are found –

(ANTERIOR LOBE)

Fig. – Gross structure of pituitary gland

1. Chromophase cells : Found in adenohypophysis of pituitary. These are not stained by acid and base dye. Pigment granules are absent. These are colourless may change into chromophils.

2. Chromophil cells : Found in adenohypophysis of pituitary. These are stained by acid and base dye. Pigment granules are filled in these cells. These may be two types –

1. Acidophils : It is also known as a-cells.
2. Basophils : It is also known as cyanophils.
   3. Pituecyte cells : These cells found in neurohypophysis of pituitary.
   4. Herring bodies : These are the bodies which store neurosecretory.

NEUROSECRETORY CELLS OF HYPOTHALAMUS

CAPILLARY BED HYPOTHALAMOHY-

POPHYSIAL PORTAL VEINS

SUPERIOR HYPOPHYSIAL ARTERY

ANTERIOR LOBE

HERING BODIES

AXON TERMINALS

3. Blood supply to pituitary : A pair of posterior hypophysial arteries and a pair of anterior hypophysial arteries provide blood to the

ADENOHYPOPHYSIS

INTERMEDIATE LOBE

PITUICYTES

VEIN               NEUROHYPOPHYSIS

pituitary gland. Posterior arteries supply blood to the pars nervosa, and   anterior arteries supply blood to the hypothalamus and pars distalis. Adenohypophysis has dual blood supply be means of a "circle of willis". The anterior hypophysial artery which bring

blood into this circle bigureates in to two branches outside the lobe. One branch supplies the adenohypophysis and other supplies the hypothalamus. The veins that drain the blood from hypothalamus. Than run into the pars distalis through pars tuberalis and divide into capillaries. Those veins are therefore, called portal hypophysial veins. These constitute a hypothalamo – hypophysial portal system.

4. Hormones                 of adenohypophysis : Adenohypophysis secrets seven hormones which are proteinous in nature. These hormones

PARAVENTICULAR NUCLEUS

SUPRAOPTIC NUCLEUS

MEDIAN EMINENCE

ANTERIOR PITUITARY

Fig. – Blood supply to pituitary

HYPOTHALAMUS

PORTAL SYSTEM INFUNDIBULUM

POSTERIOR PITUITRAY

KIDNEY TUBULES

MUSCLES OF UTERUS

controlled by the controlling factors. Secreted by the hypothalamus. These are 10 main controlling factors. Out of them 7 are releasing factor (RF) and 3 are inhibiting factor (IF). Complete failure of adenohypophysis (ant. pituitary) is leads to

simmonds syndroms. Various hormones of

MAMMARY GLAND

MUSCLE

FSH

ICSH                  LH

MELANOCYTES

ADRENAL CORTEX

adenohypophysis are as follows –

BONE           TESTIS

OVARY

(a)Somatotropin (STH) or Growth Hormone (GH)

Fig. – Diagram to show the hormones of adenohypophysis and their target tissues and organs

1. Functions of growth hormone : Molecules of this hormone are polypeptides of 191 amino acid monomers. It is the major hormone in the secretion of anterior pituitary. It is the most important stimulant of proper normal growth of body. It promotes biosynthesis of DNA, RNA and proteins in all body cells. thus, it acts as an anabolic growth factor. Obviously, it stimulates cellular growth and proliferation, growth and repair of bones, muscles and connective tissue. In the liver cells it promotes, glycogenesis, deamination and gluconeogenesis. For production of energy (ATP) in cells, it retards utilization of glucose, and promotes mobilization of fat from adipose tissues for this purpose. The overall effect of growth hormone; is, thus, an increase in body proteins and carbohydrates reserve, but decrease in body fat.

According to modern scientists, the anabolic effects of growth hormone in man are indirect, instead of being direct. This hormone triggers synthesis of certain special, insulin-like growth factors (IGFs) in cells of many tissues, such as liver, muscles, cartilages, bones, etc. These growth factors are called somatomedins. These are secreted into blood, or act as local hormones in tissues. These promote protein systhesis in cells. Unlike insulin, these promote the use of fatty acids for energy and save glucose for fertilization by nerve cells even at times of fasting and hunger. Remember that African pigmys remain dwarf simply because somatomedins are not synthesized in their bodies.

2. Control of the secretion of growth hormone : Secretion of growth hormone is controlled by two hormonal factors secreted by cells of hypothalamus. One of these factors, called GH-release hormone (GHRH) promotes secretion of growth hormone, while the other called GH-inhibatory hormone (GHIH) retards the secretion of growth hormone by the anterior pituitary. GHRH is also called somatocrinin and GHIH is called somatostatin. Under negative feedback, amounts of glucose, fatty acids and amino acids in blood affect the secretion of GH by anterior pituitary increase in a few minutes. Conversely, increasing blood levels of glucose and fatty acids, or decreasing level of amino acid promote secretions of GHIH by hypothalamus which retards secretion of GH by anterior pituitary in minutes. After termination of growth period at about the age of 22 in adolescence, secretion of growth hormone starts decreasing with age, remaining only about 25% in old age.

(3)Effects of hyposecretion of growth hormone

1. Nanism or ateliosis : Hyposecretion (undersecretion) of growth hormone is childhood results into a blunted growth of body. Growth of all organs is retarded. Growth of bones at their epiphysial ends stops. Hence, the bones do not grow in length, so that the body remains a dwarf. This pituitary dwarfism is called nanism or ateliosis.

Growth of these dwarfs can be normalised if growth hormone is given as a drug to these from the beginning in childhood. Synthetic human growth hormone (hGH) is now being manufactured on commercial scale by DNA- recombinant technique.

2. Midgets : Unlike the thyroid cretinism, the development of brain is normal in pituitary dwarfs, but like thyroid cretinism, the pituitary dwarfs are also infertile. The dwarfs of circuses are pituitary dwarfs. these are called midgets.
3. Pituitary myxodema<