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Mechanism of hormone action

Hormones (1st messengers) can act directly inside the cell (group 1) or via cell surface receptors (group 2).



Group 1

Group 2


Lipid soluble

water soluble

Transport by plasma protein



Plasma half life

Long (due to protein binding)


Mechanism of action

Receptor - hormone complex

Cell surface receptor via 2nd messenger(eg. cAMP,DAG)


1.Sex Steroids

2.Gluco corticoids & mineralocorticoids

3.Vitamin D

4Thyroid hormones

5.Vitamin A

LH, FSH, TSH, Insulin, Catecholamines



A. Nuclear receptors: Thyroid Hormones

B. Cytoplasmic receptors: Sex Steroids , Vitamin D, Gluco corticoids & mineralocorticoids

C. Cell surface receptor: Can act via either G proteins or Tyrosine Kinase mechanism.

G proteins :

G proteins are present inside the cell coupled to the cell membrane receptor.

  1. They are made up of three subunits designated αβ & γ.
  2. The α subunit is bound to GDP. When Hormone binds to the receptor GDP is exchanged for GTP and α subunit separates.
  3. This can either stimulate (Gs) or inhibit(Gi)  membrane bound enzymes like Adenyl Cyclase(cAMP), Guanylyl cyclases (cGMP) & phospholipase C via Gq (DAG & IP3).
  4. The intrinsic GTPase activity of the α subunit then converts GTP to GDP & terminate the action. DAG acts by activating protein kinase C & IP3 by increasing Ca2+.

Tyrosine Kinase: The Cell surface receptor has enzyme Tyrosine Kinase which phosphorylate receptor and then a no. of cytoplasmic proteins resulting in its action. Remember almost all GROWTH FACTORS act via Tyrosine Kinase using JAK-STAT pathway.eg NGF, IGF -1,2, PDGF, EDF etc.




 Tyrosine Kinase




Growth hormone







AT II (vascular & smooth muscle)




Substance P





IGF -1,2







Muscarinic M1 & M3(Acetylcholine)

Growth Factors



ADH (V1 receptor)






ADH (V2 receptor)


α11 adrenergic















α 2(-) & β adrenergic




Somatostatin (-)




M2  Muscarinic (-)





Note: (-) denotes inhibit Adenyl Cyclase.


Pituitary Gland:  Growth Hormone & Prolactin

  1. The pituitary gland, or hypophysis, is an endocrine gland present in sella turcica covered by a dural fold (diaphragma sellae).
  2. The pituitary fossa, in which the pituitary gland sits, is situated in the sphenoid bone in the middle cranial fossa. It Develops from called Ratheke's pouch.
  3. It has 3 divisions: Adenohypophysis (Anterior Pituitary), Intermediate lobe( secrete α MSH) & Neurohypophysis (Posterior Pituitary which secrete Oxytocin & ADH).
  4. Anterior has 2 type of cells ACIDOPHILS [secrete Growth hormone from Somatotrope (most common cell type) & Prolactin from Lactotrope] & BASOPHILS (secrete ACTH, TSH, LH & FSH).

Growth Hormone

  1. The long arm of human chromosome 17 contains gene for growth hormone and hCS.
  2. The plasma growth hormone level is less than 3 ng/mL.
  3. The half-life of circulating growth hormone in humans is 6–20 min.
  4. Daily growth hormone output is 0.2–1.0 mg/day in adults.
  5. It acts via Tyrosine Kinase using JAK-STAT pathway

Stimulators of GH secretion include:

Inhibitors of GH secretion include:


REM Sleep

Propranolol (by inhibiting somatostatin)

Somatostatin from the periventricular nucleus

Deep sleep

Circulating concentrations of GH and IGF-1



Protein diet & amino acids like arginine


Vigorous exercise


ADH, Glucagon, Ghrelin


GHRH also known as somatocrinin


Increased androgen & estrogen secretion


Clonidine and L-DOPA by stimulating GHRH release




1. Increases the mineralization of bone & epiphyseal growth

2. Ketogenic and increases circulating free fatty acid (FFA) levels

3. Promotes lipolysis & decrease in plasma cholesterol

4. Increases protein synthesis and increases muscle mass

5. GI absorption of Ca2+ is increased and produces a positive nitrogen & phosphorus balance

6. Stimulates the growth of all internal organs excluding the brain

7. Reduces liver uptake of glucose, decreased insulin sensitivity (diabetogenic)

8. Promotes gluconeogenesis in the liver

9. Excretion of the amino acid 4-hydroxyproline is increased(collagen synthesis)

10.GH stimulates production of somatomedin like insulin-like growth factor 1 (IGF-1) from liver

  1. The effects of growth hormone on growth, cartilage, and protein metabolism depend on an interaction between growth hormone and somatomedins, which are polypeptide growth factors secreted by the liver and other tissues.
  2. The first of these factors isolated was called sulfation factor because it stimulated the incorporation of chondroitin  sulfate into cartilage.
  3. However, it also stimulated collagen formation, and its name was changed to somatomedin. It then became clear that there are a variety of different somatomedins and that they are members of an increasingly large family of growth factors that affect many different tissues and organs.
  4. The principal (and in humans probably the only) circulating somatomedins are insulin-like growth factor I (IGF-I, somatomedin C) and insulin-like growth factor II (IGF-II). These factors are closely related to insulin, except that their C chains are not separated


Hypophysectomized animals have a tendency to become hypoglycemic, especially when fasted. Hypophysectomy ameliorates diabetes mellitus and markedly increases the hypoglycemic effect of insulin. This is due in part to the deficiency of adrenocortical hormones, but hypophysectomized animals are more sensitive to insulin than adrenalectomized animals because they also lack the anti-insulin effect of growth hormone.


  1. It is a luteotropic hormone & gene encoding prolactin is located on chromosome 6.
  2. The normal plasma prolactin concentration is approximately 5 ng/mL in men and 8 ng/mL in women.
  3. Secretion is tonically inhibited by hypothalamic prolactin-inhibiting hormone (PIH) i.e.dopamine from tuberoinfundibulum (TIDA) neurons of the arcuate nucleus.
  4. It stimulates the mammary glands to produce milk (lactation)
  5. Prolactin provides the body with sexual gratification after sexual acts. The hormone counteracts the effect of dopamine, which is responsible for sexual arousal. This is thought to cause the sexual refractory period.
  6. Unusually high amounts are suspected to be responsible for impotence and loss of libido.
  7. Prolactin also stimulates proliferation of oligodendrocyte precursor cells.
  8. Prolactin increases surfactant synthesis of the fetal lungs
  9. Factors increasing its production are: Sleep, Nursing, Breast stimulation, Stress, Hypoglycemia, Strenuous exercise, Sexual intercourse in women, Pregnancy (maximum), Estrogens (maximum), Hypothyroidism, TRH, Opioids & Somatostatin.

HIGH prolactin is associated with: (AIIMS Nov 09)

a. Increase FSH                    
b. Increase estradiol
c. Increase testosterone  
d. Increase libido



Increase estradiol

High prolactin levels tend to suppress the ovulatory cycle by inhibiting the secretion of both follicle-stimulating hormone (FSH) and gonadotropic-releasing hormone (GnRH). They also result in decreased levels of both testosterone and estrogens.


Kisspeptin the product of the gene Kiss1 is a G-protein coupled receptor ligand for Kiss1 was originally identified as a human metastasis suppressor gene that has the ability to suppress melanoma and breast cancer metastasis. It is recently become clear that kisspeptin-GPR54 signaling has an important role in initiating GnRH secretion at puberty. Before puberty the GnRH neurons are under inhibition by GABA.mcq

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