Endocrine System

Endocrine System ENDOCRINE SYSTEM Along with nervous system the endocrine system also plays role in integrating and coordinating the body functions, but it is a slow and persistent mode compared to nervous system. Acts through chemical messenger called hormones at the level of target cells / tissues. Endocrine glands release hormone directly into blood (within itself), hence called endocrine. (endon = within ; crine = secrete) Blood carries it all around (upto target cells) in the body. The study of endocrine glands and hormones secreted by them is known as endocrinology. BRIEF HISTORY Berthold (1849) first showed the loss of secondary sexual characters in cocks by removal of testes. Schiff (1854) reported animal dying after removal of thyroid gland. Claude Bernard (1855) established the control of endocrine glands by nervous system Addison (1855) demonstrated the symptoms of disease (i.e. the Addison’s disease) in human by removing the cortical part of adrenal gland, he is therefore, called as Father of Endocrinology. Hormones (Gr. Hormaein = to excite) Hormones are the biologically active, organic substance which acts as chemical messenger to alter the metabolic processes of target cells, the term was coined by Starling and Bayliss (1902). Stimulates or inhibits bio-chemical reactions effectively even in low doses e.g. 1 gm of adrenalin is sufficient to stimulate 10 million isolated frog’s heart. Not found in the food but is only synthesized in the body and released only in response to the body requirement. For prolonged effect it is continuously secreted by the concerned gland. Not stored in the body but is eliminated with urine in the same or in degraded form if not used. In blood in remains bound with plasma proteins as its carrier hence, remains inactive No direct involvement in metabolic reactions but influences the activity. Some hormones have wide range action affecting most cells in the body but most hormones affect only specific target cell or specific activity of the cells. The target cells have specific receptors for concerned hormone. The chemical nature of most hormones are common in various animal species (except a few protein hormone), hence the hormone extracted from one animal is effective also in other animal species. Hormonal disorder (hyposecretion or hypersecretion) causes disease/defects in the body. TYPES OF HORMONES Chemically of two types : (i) Proteinoid and (ii) Steroid hormone with different types of influence upon the cellular processes. - 140 - Endocrine System 1. Proteinoid hormones are amino acid, polypeptides, proteins and glycoproteins. They not enter the cell but accomplish their effects at the membrane level in two following ways : (a) It alters the permeability of membrane there by allowing various substances to cross through. (b) It stimulates the enzyme cascade of the cell membrane, most common is adenyl cyclase enzyme which mediates the formation of cyclic-AMP (c-AMP) from ATP. c-AMP acts as second messenger to affect the cellular metabolism in various ways (Sutherland) 2. Steroid hormones are lipids or derivatives of fatty acids which can directly enter the target cell and affect the gene activity inducing the synthesis of specific protein (or enzymes) or suppressing the activity of other genes. This involves the synthesis of enzymes or stopping it. Thyroid hormones, though proteinoid type (amino acids), acts as steroid hormones. CONTROL OF HORMONE SECRETION Secretion of many hormones are under direct control of hypothalamus which secretes the’ releasing hormone’ (RH) or inhibiting hormone (IH) for the concerned hormones ; e.g. GHRH (Growth hormone releasing hormone) and GHIH (Growth hormone inhibiting hormone). FEED BACK CONTROL The release of any hormone and its amount depend upon its own level in the blood. It’s higher level inhibits its secretion while its low level enhances its secretion. This is also popularly known as pull and push or plus minus control. HORMONE ACTION Molecular Mechanism of Hormone Action : Catecholamines, peptides and protein hormones are not lipid soluble hence cannot enter the target cells. They interact with surface receptor, usually a glycoprotein, which initiates chain of events that varies for different hormones, finally coming to intracellular receptors. Example of insulin action is well explained as follows : Extracellular receptors Receptors for insulin is a heterotetrameric protein with 4 units – two α –subunits protruding outside on the cell surface which binds with insulin and two β-subunits that protrude in the cytoplasm. In most cells such receptors are about 100/cell but in liver cell more than a lakh are present. MECHANISM - 141 - Endocrine System (i) Binding to the receptor Insulin binds to α-subunit, causes conformational change in β-subunit of receptor which is actually an enzyme tyrosine kinase – which add phosphate group to tyrosine residue of cytoplasmic receptor. Cytoplasmic (second) messengers G-protein along the inner (cytoplasmic) face of membrane which acts as transducer activates the enzyme phosphodiesterase which changes phosphatidylinositol 4, 5-biphosphate (PIP2) into a pair of mediators. (I) Inositoltriphosphate (IP3) and diacylglycerol (DG or DAG). IP3 is water soluble hence diffuses into cytoplasm and triggers the release of Ca2+ activating various mediated cellular processes. DG remains along the membrane and activates another enzyme, protein kinase C (PKC) which then activates many other enzymes, e.g., pyruvate dehydrogenase. The lipid portion of DAG is arachidonic acid which is precursor of prostaglandins. (ii) - 142 - Endocrine System (iii) Amplification of Signal - These above said mediators amplify the signal, e.g., 1 β-subunit activates many DG molecules and each protein kinase C activates many other enzyme molecules. DG and IP2 act as second messengers. Variety of hormones also use other second messenger e.g., cAMP. The enzyme adenyl clyclase (in membrane) converts ATP into cAMP. A single adenyl cyclase can produce about 100 molecules of cAMP. Some hormones also use cGMP as second messenger e.g., ANP (atrial natriuretic peptide) acts through cGMP. ACTION OF ADRENALINE - 143 - Endocrine System In muscle cell or liver cell when adrenaline bind to receptors they change shape and bind to GTP which binds with another molecule of adenyl cyclase. This complex cascade then produces large amount of cAMP. cAMP activates the enzyme protein kinase A each molecule of which in turn activates > 100 molecules of enzyme phosphorylase kinase. As a result a single molecule of adrenaline can cause the release of 100 million of glucose molecule within 1 or 2 minutes. INTRACELLULAR RECEPTORS The steroid and thyroid hormones enter the cell directly and bind to the intracellular receptor protein in the cytoplasm, this complex enters nucleus and bind to the specific regulatory sites on chromosome. This alters the pattern of gene expression – initiating its transcription, formation of specific mRNA and then protein (enzyme). The action of lipid soluble hormones are slower and last longer than the effects of water-soluble hormones. ANTAGONISTIC EFFECT Many cells use more than one second messenger. In heart cells cAMP serves as second messenger for adrenaline to increase the heart rate, while cGMP for acetylcholine slows the heart rate. This is how sympathetic and parasympathetic nervous system achieve antagonistic effect. Insulin and glucagons hormones are antagonistic in action. SYNERGISTIC EFFECT Sometimes two or more hormones complement each other’s actions and both are needed for full expression of their effects, e.g., production, secretion and ejection on milk from mammary gland is effected by estrogen, progesterone, prolactin and oxytocin. PITUITARY GLAND (HYPOPHYSIS) Attached to the ventral side of hypothalamus this is a single pea-sized gland once considered as master gland (Vesalius) for its control over all endocrine glands. Lodged in depression called sella turcica, along the floor of the sphenoid bone, it remains connected through a stalk called infundibulum, with hypothalamus. The average size in human is 0.38 to 0.98 cm (diameter) and weights 0.5 to 1 gm, (larger in pregnant females). Structure Division and origin of the respective parts of pituitary gland can be best depicted by the following chart : - 144 - Endocrine System Adenohypophysis arises from the dorsal wall of stomodaeum (oral ectoderm) as Rathke’s pocket which later detaches from here and attaches with the neurohypophysis. Neutrohypophysis is directly the hypothalamic part projecting down, into pituitary, here the hormone (neurosecretion) loaded cells appear as Herring bodies in stained preparation. Pars tuberalis is the upper smaller part having tubular shape around the stalk of anterior lobe. It mainly secretes gonadotropins and lactotropins. Pars distalis is the main, largest (75%) part of pituitary. It has five types of cells related to the secretion of respective hormones : (i Acidophils – GH and LTH, (ii) Basophils – TSH, ACTH, FSH, LH. HORMONE OF ANTERIOR (ADENOHYPOPHYSIS ) PITUITARY 1. Growth Hormone (GH) or Somatotrophic Hormone (STH) - 145 - Endocrine System It is secreted by somatotrophes; consisting one polypeptide chain of 191 amino acids. Its secretion is stimulated by the GHRH (growth hormone releasing hormone) from hypothalamus : It induces growth of tissues, organs or body, enhances rate of mitosis, protein synthesis, fat mobilization and glucose utilization and inhibited by GHIH (growth hormone inhibitory) from hypothalamus. Influences mainly the growth and thickening of bones. Its hyposecretion causes dwarfism (or ateleosis). The circus clowns (midgets) are this type of dwarf. They are sound both mentally and sexually. It also causes Simmond’s disease. Hypersecretion in childhood and teens causes gigantism while in grown up causes acromegaly. In acromegaly only end parts of the body grow, viz the end of fingers and toes, chin, ear lobes, nose tips, supra orbital ridge etc. enlargement of scapula and vertebrae causes hunch back (or kyphosis). 2. Adrenocorticotrophic Hormone (ACTH) Control the growth and maintenance of adrenal cortex and its secretions which maintain the level of glucose, mineral and ions. Its secretion is stimulated by ACRH from hypothalamus while inhibition is by negative feed back. 3. Thyroid Stimulating Hormone (TSH) Glycoprotein in nature it controls the growth and functioning of thyroid gland (synthesis and release of its hormones) to control over all metabolism of the body. Its secretion is triggered by TRH from hypothalamus while inhibition occur through negative feed back (high level of thyroxine). 4. Leuteotrophic Hormone (LH) Influences the formation and growth of corpus luteum (yellow body) from the ruptured Graafian follicle in ovary after ovulation. Induces ovulation and its high level inhibits the maturation of new follicles. In male the same hormone is called as interstitial cell stimulating hormone (ICSH) which influences the cells of Leydig (or interstitial cell) of testis of secrete testosterone (androgen). Its release is triggered by LHRH from hypothalamus while inhibition is made by its own increased level. 5. Follicle Stimulating Hormone (FSH) Control the growth and maturation of primary follicles (oogenesis) in ovary and spermatogenesis in the seminiferous tubules. Secretion of this hormone is triggered by FSHRH from hypothalamus and inhibition by its own level. It marks the onset of puberty. 6. Prolactin/Lactogenic Hormone (LTH)/Mammotrophic Hormone (MTH) Growth and maintenance of mammary glands for production of milk. The activity of this hormone begins during pregnancy, hence, there is also the synergistic effect of other hormones upon it. Its secretion and inhibition is triggered by PRH and PRIH respectively from hypothalamus. 7. Melanocytes Stimulating Hormone (MSH) Secreted by pars intermedia (intermediate lobe) so also called intermedin. Activates melanocytes to secrete melanin for the colouration of skin. Its secretion and inhibition is respectively influenced by MSHRH and MSHIH from the hypothalamus. In human it is also called vestigeal hormone. Hormones of Posterior Pituitary (Neurohypophysis) 1. Antidiuretic hormone (ADH or Vasopressin or Pitressin) : • The osmoregulation hormone controls the volume of urine by increa