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Hormone is a substance produced in one part of body enters the circulation and is carried to distant target organs and tissues to modify their structure and functions.

Target cell is defined by its ability to bind selectively a given hormone via a receptor.

Receptors Has:
Recognition Domains – that binds hormones.
Coupling Domain – generates a signal that couples Hormone recognition to some intracellular function.


  1. Based on Location of Receptor
    1. Hormones that bind to Intracellular receptor e.g.


Intracellular Receptors

Cytoplasmic receptors

Nuclear receptors


Thyroid hormones


Vitamin A







Vitamin D


  1. Hormones that bind to cell surface receptors
    1. The second messenger is cAMP, e.g. Catecholamines, ACTH, ADH, Calcitonin, CRH, FSH, LH, MSH, TSH, PTH, hCG
    2. Second messenger is cGMP e.g. Atrial natriuretic factor (ANF), Nitric oxide (NO)
    3. The second messenger is calcium or phosphatidyl inositol or both e.g. TRH, GnRH, Platelet derived growth factor, oxytocin, substance P, ADH, Angiotensin II.
    4. The second messenger is kinase or phosphatase cascade.
      e.g. Insulin, Prolactin, Insulin like growth factor 1GI & 1G-II, GH, Fibroblast growth factor, epidermal growth factor (EGF).

B. Classification as group i and group II



Group I

Group II




Transport Proteins



Plasma half life

Long (hours to day)

Short (minutes)



Plasma membrane


Receptor – Hormone complex




Extra Edge
Class II hormones, which bind to cell surface receptors, generate a variety of intracellular signals. These include cAMP, cGMP, Ca2+, phosphatidylinositide, and protein kinase cascades.

Second Messenger – Hormone binds to the surface of cell and communicate with the intracellular metabolic processes through intermediary molecules cells second messengers.


C.   G-Proteins

  1. G proteins consist of 3 subunits α, β & γ – The α-subunits binds to GTP or GDP. The β & γ subunits do not
  2. bind nucleotides, they bind to α- subunit.
  3. Hormone receptor complex catalyses the exchange for GDP by G Protein, when GDP is exchanged for GTP or α subunit.  G - GTP dissociates from Gβγ. Gα-GTP is the active form
    1. Types of G Proteins– Gs – stimulates enzyme adenylate cyclase Gi– inhibits enzyme adenylate cyclase, Gq – stimulates enzyme phospholipase C.
    2. Function – Gα subunits of all G-Proteins is a GTPase. It slowly hydrolyzes GTP to GDP results to in active GDP bound state.
    3. Cholera Toxin : Is an enzyme produced by bacterium vibrio cholerae.
      1. It Causes ADP – ribosylation of αs- subunits by doing so it inactivates GTPase so blocks hydrolyses of GTP to GDP. This prevents the in activation of Gs by this mechanism.
      2. Result– Persistent high level of CAMP which causes epithelial cell of intestine to transport sodium ions & H2O into intestinal lumen & diarrhea.
  4. Pertussis Toxin: Irreversibly activates adenylyl cyclase by promoting ADP ribosylation of α1 unit preventing it from being activated.
  5. Protein Kinases: cAMP binds to protein kinase, heterodimeric molecule consisting of two regulatory subunits R2 & two catalytic subunits C. R2 C2 complex has no enzymatic activity.

4 CAMP + R2 C2  D R2 (4 CAMP) + 2 C

active C subunits catalyses the transfer of γ phosphate of ATP to serine & threonine residues in variety of proteins.


Classes and Functions of Selected G Proteins1


Class or Type









âAdenylyl cyclase

âCardiac Ca2+, Cl, and Na+ channels

âAdenylyl cyclase


lipolysis, glycogenolysis






Acetylcholine, 2-


M2 cholinergics

Opioids, endorphins


âAdenylyl cyclase

âPotassium channels

âCalcium channels

âPotassium channels

âcGMP phosphodiesterase

Slowed heart rate

Neuronal electrical activity





M1 cholinergics



âPhospholipase C-β1

âPhospholipase C-β2

âMuscle contraction


âBlood pressure







  1. Hormones That Act Through Calcium Or Phosphatidylinositol
    Phospholipase C catalyzes the hydrolysis of phosphatidylinositol 4,5 bisphosphate to inositol bisphosphate
    (IP3) and 1,2 diacylglycerol. DAG is itself capable of activating Protein kinase C. IP3 by interacting with a specific intracellular receptor, is effective releaser of calcium from intracellular storage site such as sarcoplasmic reticulum or mitochondria.
  2. Hormones That Act Through A Protein Kinase Cascade
    Hormones in this category specific is that kinases phosphorylate tyrosine residues. Tyrosine kinase activation also initiates phosphorylation & dephosphorylation cascades.

Pituitary & Hypothalamic Hormones

Hypothalamic Hormone

Pituitary Hormone affected

Corticotropin releasing Hormone (CRH)

Thyrotropin releasing Hormone (TRH)

Gonadotropin releasing Hormone (GnRH)

Growth Hormone releasing Hormone (GRH)

Growth Hormone release inhibiting Hormone or somatostatin (GHRIH)

Prolactin release inhibiting Hormone Dopamine & GAP

ACTH (LPH, MSH, endorphins)







Classification of Anterior Pituitary Hormones

A.  Growth Hormone, Prolactin, chorionic somatomammotropin group.


B.  Glycoprotein Hormone Group.


C.  Pro-opiomelanocortin peptide family

Group I

  1. Growth Hormone (GH), Prolactin (PRL) & chorionic somatotrophin (CS), are a family of protein hormones with considerable sequence homology.
  2. GH, PRL & CS range in size from 190-199 amino acid, each has single tryptophan residue & two homologous disulfide bones.
  3. Hormones are produced in tissue specific manner with GH and prolactin produced in anterior pituitary & CS in the syncytiotrophoblast cells of placenta.
  1. Growth Hormone
    Synthesized in somatotropes, pituitary acidophil cells. The concentration of GH in pituitary is 5-15 mg/g. GH is a single polypeptide with 191 amino acids & molecular mass of 22 kDa. 

  2. Prolactin

    1. Prolactin is a protein hormone, molecular mass 23kDa, & it is secreted by Lactotropes with increase and size and number during pregnancy.
    2. PRL is involved in initiation & maintenance of lactation in mammals.
    3. Tumors of Prolactin secreting cells cause amenorrhea & galactorrhoea in women. Excessive prolactin has been associated with gynecomastia and impotence in man. 

Group II

  1. Glycoprotein Hormones e.g., thyroid stimulating hormone (TSH), follicle stimulating Hormone (FSH) & Luteinizing Hormone (LH), and chorionic gonadotropin (hCG).
    1. Each of these hormone consists of two subunits α and β joined by noncovalent binding. The α- subunits are identical for all these hormones within a species. The specific biologic activity is determined by â-subunit.
    2. Human chorionic gonadotropin (hCG) – hCG is glycoprotein synthesized is the syncytiotrophoblast cells of placenta. It increases in blood & urine shortly after implantation hence its detection is the basis of many pregnancy tests.

Group III

1.  Pro-opiomelanocortin Peptide family (POMC family)

  1. Proopiomelanocortin family consists of peptides that act as Hormones (ACTH, LPH & MSH) and others that serve as neurotransmitter.
  2. POMC is synthesized as a precursor molecule of 285 amino acids and is processed differentially in various regions of pituitary.

2.  Acth

  1. ACTH is a single chain polypeptide consisting of 39 amino acids regulates the growth & function of adrenal cortex.
  2. ACTH increases the synthesis & release of adrenal steroids by enhancing conversion of cholesterol to pregnenolone.
  3. Since pregnenolone is precursor of all adrenal steroid, so prolonged ACTH stimulation results in excessive production of steroid hormone.
  4. Excessive production of ACTH by pituitary or by ectopic production from tumor result in Cushing syndrome.

3.  β– Lipotropin (β–LPH)

  1. This peptide consists of carboxy treatment 91 amino acid of POMC.
  2. β-LPH contains the sequences of β-MSH, γ-LPH, met-enkephalin and β endorphins.
  3. β-LPH causes lipolysis and fatty acid mobilization but its physiologic role is minimal.
  4. Endorphinsβ–endorphins consists of carboxy terminal 31 amino acids of β-LPH.
  5. Endorphins bind to some CNS receptor as do opiates and the play role in endogenous control of pain perception.
  6. Endorphins have higher analgesic potency (18-30 times) than morphine.
4.  MSH

MSH stimulates melanogenesis by causing dispersion of intracellular melanin granules resulting in darkening of skin.

Hormones of Posterior Pituitary


Vasopressin / Antidiuretic Hormone and Oxytocin

  1. These Hormones, each is nonapeptide containing cysteine molecules at position 1 and 6 linked by an disulphide bridge.
  2. Oxytocin– Stimulates contraction of uterine smooth muscle and myoepithelial cells surrounding mammary alveoli. This promotes the movement of milk into alveolar duct system and allows milk ejection.
  3. Antidiuretic Hormone (ADH) Reabsorbs water by acting on the cells of distal convoluted tubules and collecting ducts in kidney.
  4. Abnormality of ADH secretion or action leads to Diabetic insipidus characterized by excretion of large volume of dilute urine.

Hormones of Pancreas & Gastrointestinal Tract

Endocrine portion of Pancreas is known as Islets of Langerhans and secretes hormones
Insulin, glucagon, somatostatin and Pancreatic polypeptide
  1. Insulin
    1. Insulin is a polypeptide consisting of two chains A and B linked by interchain disulfide bridges that connect A7 to B7 and A20 to B19. A third intrachain disulfide bridge connects residues 6 & 11 of A chain. A & B chain have 21 and 30 amino acids respectively.
    2. Insulin is Synthesized as Preprohormone (not wt ~ 11, 5000). The hydrophobic 23-amino acid leader sequence directs the molecule into cisternae of endoplasmic reticulum is removed that results in 9000 molecular weight proinsulin which undergoes a series of site specific peptide cleavages & results in formation of equimolar amount of mature insulin & c-peptide.
    3. c-peptide – has no known biologic activity & is distinct molecule from an antigenic standpoint.
    4. c-peptide immunoassay can distinguish b/w insulin secreted endogenously from insulin    administered exogenously.
    5. Secretion of Insulin : A normal man secretes 50 units of Insulin per day & secretion is influenced by no. of factors.
      1. Blood glucose — An increase in plasma insulin concentration is most important physiologic regulator of insulin secretion.
      2. Hormonal factor
        1. α-adrenergic agonist , principally epinephrine inhibits insulin release
        2. β-adrenergic agonist stimulate insulin release, probably by increasing intracellular CAMP.
      3. Pharmacologic agents – Many drugs stimulate insulin secretion for eg. Sulfonylurea compounds.

Insulin Receptors – glycoprotein, heterodimer consisting of two submits α and β in configuration α2β2linked by disulfide bond. The α-subunit is entirely extracellular & binds insulin probably via a cysteine rich domain.

β-subunit is a transmembrane protein that performs the function of signal transduction, the cytoplasmic portion of. β subunit has tyrosine kinase activity and autophosphorylation site. Both of these are involved in signal transduction and insulin action. 

Metabolic Role & Functions of Insulin

1. The net effect of Insulin is to lower blood glucose level and to increase glycogen store.


  1. Insulin increases glucose uptake by various tissues.
  2. Insulin increases hepatic glycolysis & amount of several key enzymes including glucokinase, phosphofructokinase & pyruvate kinase.
  3. Insulin decreases the activity of glucose–6–Phosphatase an enzyme found in liver not in muscle.
  4. In skeletal muscle, insulin promotes glucose entry through the transporter also increases hexokinase II which phosphorylates, Glucose & initiates metabolism.

Action on Lipid Metabolism – Insulin stimulates lipogenesis in adipose tissue.

  1. By providing acetyl CoA and NADPH required for fatty acid synthesis
  2. By maintaining a normal level of enzyme acetyl CoA carboxylase
  3. Stimulates glycogenesis in liver & muscle by increasing dephosphorylation of key & rate limiting enzyme “glycogen synthase” thus converting it to active form
  4. Insulin reduces gluconeogenesis – Insulin selectively inhibits transcription of gene that codes for mR NA for Phosphoenol pyruvate carboxykinase, the key enzyme of gluconeogenesis.
  5. Insulin increases HMP-shunt activity by inducing the synthesis of Glucose-6-Phosphate dehydrogenase and 6-phosphogluconate dehydrogenase.
Effect on protein metabolism
  1. Insulin generally has an anabolic effect on protein metabolism as it stimulates protein synthesis and retards protein degradation.
  2. Insulin stimulates the uptake of neutral amino acid into muscle.

F.  IGF-I and IGF-II

  1. IGF-I and IGF-II are related to Insulin in structure & function.
  2. IGF-I and IGF-II are single chain peptides of 70 or 67 amino acids respectively there is 62% homology b/w IGF-I and IGF-II & these 2 hormones are identical with insulin in 50% of their residues.
  3. IGF-I receptor like insulin receptor is a heterodimer of α2β2 structure and is tyrosine kinase.
  4. IGF-I & Insulin use a very similar signal transduction cascade.
  5. IGF-II receptor is a single chain polypeptide with a molecular mt. of 2,60,000 and is not tyrosine kinase

Pathophysiology Involving Insulin is expressed as Diabetes Mellitus

  1. Type I or Insulin dependent diabetes mellitus (IDDM)
  2. Type II or Non insulin dependent diabetes mellitus (NIDDM)
  3. Cardinal manifestation of diabetes mellitus is Hyperglycemia which results from
    1. decreased entry of glucose into cells
    2. decreased utilization of glucose by various tissues
    3. increased production of glucose (gluconeogenesis) by liver.


Diabetic Ketoacidosis
  1. Diabetic ketoacidosis appears to require Insulin deficiency coupled with relative or absolute increase in glucagon concentration. These Hormonal changes have multiple effects but two are critical.
    1. They induce maximal gluconeogenesis & Impair peripheral utilization of glucose causing severe hyperglycemia. The resulting hyperglycemia induces osmotic diuresis that leads to volume depletion and dehydration that characterize ketoacidotic-state
    2. They activate the ketogenic process & thus initiate the development of metabolic acidosis.
  1. Glucagon
    1. Synthesized in A cells of Pancreatic islets, is a single chain polypeptide consisting of 29 amino acids.
    2. Glucagon circulates in plasma in free form. Since, it does not associate with a transport protein its plasma half life is short about 5 minutes
    3. In general glucagon opposes the actions of insulin.
      1. Glucagon causes potential mobilization of energy sources into glucose by stimulating Glycogenolysis & lipolysis
      2. Liver is the primary target of glucagon action 

Hormones of Adrenal Cortex


A.  Adrenal cortex produces glucocorticoids, mineralocorticoids and androgens.

B.  Glucocorticoid primarily affect the metabolism of carbohydrates, protein & lipid with relatively minor effect on electrolyte & water metabolism e.g. cortisol and corticosterone.

Mineralocorticoid which primarily affect the reabsorption of Na+ and secretion of K+ and distribution of water m tissues e.g.; Aldosterone, 11-deoxy corticosterone and 11-deoxy cortisol.


Androgens & estrogen —
Primarily affect secondary sexual characters.


1.   Synthesis

  1. Adrenal steroid Hormone are synthesized from cholesterol. Upon stimulation of the adrenal by ACTH, cholesterol transported into mitochondria where a cytochrome P450 side chain cleavage enzyme (SCC) converts cholesterol to Pregnenolone.
  2. All mammalian steroid Hormones are formed from cholesterol via pregnenolone through a series of reactions that occur in either mitochondria or endoplasmic reticulum of adrenal cells.


  1. Plasma transport – cortisol circulates in plasma in protein bound & free form the main Plasma binding protein is α-globulin called transcortin or corticosteroid binding globulin which is produced in liver.
  2. Mineralocorticoid does not have any specific plasma transport protein but forms a very weak association with albumin.

2.   Regulation of Synthesis

  1. Glucocorticoid Hormone – secretion of cortisol is dependent on ACTH which in turn is regulated by CRH (Corticotropin releasing hormone).
  2. Mineralocorticoid – the production of aldosterone from glomerulosa is regulated by renin-angiotensin system & potassiu



3.   Actions of Mineralocorticoids

  1. Increase rate of tubular reabsorption of Na+ by acting at distal convoluted tubules and collecting duct
  2. These hormones also promote secretion of K+, H+ & NH4+ by kidney so net effect of mineralocorticoid is Na+ retention & K+ secretion.

4.   Disorders of Glucocorticoid Hormone Insufficiency & Excess

  1. Addison’s disease – Primary adrenal insufficiency results in hypoglycemia, intolerance to stress, low blood pressure, Plasma Na+ levels are low, K+ Levels are high & Plasma lymphocytes & eosinophil counts are increased such patients show increased pigmentation because of exaggerated compensatory secretion of ACTH.
  2. Cushing syndrome: Of Glucocorticoid excess 

5.   Disorders of minerals corticoid Excess

Conn’s syndrome – Classic manifestation include Hypertension, Hypokalemia, Hypernatremia & Alkalosis.

Thyroid Hormones

  1. Thyroid hormones are:

    1. Thyroxine (T4) (3,53’5’ Tetraiodothyronine)
    2. Tri-iodothyronine T3 (3,5 3’ – Tri-iodothyronine)      
    3. Reverse T3. (3,3,5’ – Tri-iodothyronine)

Biosynthesis of Thyroid Hormones –Require (1) Thyroglobulin (2) Iodine


B. Thyroglobulin

  1. Is a large, Iodinated, glycosylated protein with molecular mass 660 KDa
  2. Is composed of two subunits & it contains 115 tyrosine residue which are potential site of Iodination.
  3. About 70% of Iodide in thyroglobulin exists as monoiodotyrosine (MIT) and di-iodotyrosine (DIT) while 30% is in the form of Iodothyrosyl residues T4 & T3
  4. When Iodine supplies are sufficient T4:T3 ratio is 7:1, in Iodine deficiency, this ratio decreases.
  5. Iodide – Ingested dietary Iodine is converted to Iodide with an average uptake of Iodide, daily Iodide requirement is between 150 and 200μg3.
  6. Transport of thyroid Hormones :- One half to two third of T4 and T3 hormones are extrathyroroidal and circulates by binding to 2 proteins : Thyroxine binding globulin TBG and thyroxine binding pre albumin (TBPA)
    1. TBG – is glycoprotein with molecular mass 50 kda , it binds T4 and T3 with 100 times the affinity of TBPA under normal circumstances, TBG binds non covalently to nearly all of the T3 and T4 in plasma the small unbound fraction is responsible for biologic activity. Plasma half life of T4 is four to five times that of T3.
      1. T3 is the metabolically active form of the molecule.
      2. Reverse T3 is very weak agonist is made in relatively large amount in chronic disease, carbohydrate starvation and in the foetus.
  7. Normal range T4-60—150- nmoL/L and T3-1-3nmoL/L & 0.2-0.6 nmoL/L for reverse T3

C.  Function of Thyroid Hormone

  1. A major effect of T3 & T4 is to enhance general protein synthesis and causes positive nitrogen balance.
  2. Lipid metabolism – increased lipolysis
  3. Effect on cholesterol — hormone increases the rate of biosynthesis of cholesterol. They increase (i) the rate of degradation (ii) increases the formation of bile acids (iii) increases biliary excretion & to a greater extent.
  4. Effect on carbohydrate metabolism
    1. Thyroid hormone increases rate of absorption of glucose from intestine
    2. Hepatic glycogenolysis
    3. Stimulate glycolysis as well as oxidative metabolism of glucose in a TCA cycle
    4. Thyroid hormone increase hepatic gluconeogenesis by increasing activities of pyruvate carboxylase & PEP carboxykinase

5.  Thyroid hormone is important modulator of developmental process. this is most apparent in amphibian metamorphosis.


Recent Advances

Tamoxifen and Targeting of Estrogen Receptor

  1. Tamoxifen, a drug used w treat breast cancer, is a competitive inhibitor of the estrogen receptor (ER). Breast cancer cells respond to normal estrogen by increasing their proliferation rate. Estrogen activates the estrogen receptor, whereas tamoxifen prevents normal activation and reduces transcription from genes regulated by the estrogen receptor, and hence reduces growth of breast cancer cells.
  2. However, tamoxifen treatment can increase the risk of uterine cancer. The apparent cause lies in the presence of two estrogen receptor subtypes (α and β). Both subtypes exist in breast tissue but estrogen receptor-α predominates in uterine tissue. In uterine tissue tamoxifen apparently activates receptor-α, rather than inhibiting it. The result is stimulation of transcription in conjunction with transcription factors fos and jun.

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