Hormones & Hormones Antagonists

8/13/2019 Hormones & Hormones Antagonists

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Hormones & Hormones

antagonists

• Anterior and Posterior Pituitary hormones

• Corticosteroids and corticosteroid antagonists

• Thyroid and antithyroid drugs, parathyroid hormones, drugs regulating

calcium homeostasis, Vitamin D

• Insulin, Oral hypoglycemic agents, glucagon

• Gonadal hormones and Oral contraceptives, antifertility agents

• Oxytocin and drugs acting on uterus.



Hormone

It is a substance of intensebiological activity that is

produced by specific cells in

the body and is transported

through circulation to act onits target cells.

Hormones regulate body functions to bring about a

programmed pattern of life events and maintainhomeostasis

These are secreted by the endocrine glands. These are



Pituitary Hormones



Thyroid Hormones

Thyroid gland is responsible for the secretion of three

hormones essential for proper regulation of metabolism.

Thyroxine (T4)- Follicular cells

Triodothyronine (T3)- Follicular cells Calcitonin- Parafollicular cells

Parathyroid Hormones

Parathormone (PTH)



Pancreas

The pancreas has two mainfunctions:

[1] to produce pancreatic

endocrine hormones

(e.g., insulin & glucagon)which help regulate many

aspects of metabolism and

[2] to produce pancreatic

digestive enzymes.



Adrenal Gland

Cortex: Glucocorticoids (Hydrocortisone)

Mineralocorticoids (Aldosterone)

Sex steroids (Dehydroepiandrosterone)

Medulla: Adrenaline, Noradrenaline



Gonads

Androgens (Testosterone)

Estrogens (Estradiol)

Progestins (Progesterone)



In addition,

Hypothalamus produces many releasing and

inhibitory hormones which control the secretion ofanterior pituitary hormones

Placenta also secrets many hormones

Chorionic gonadotropin

Estrogens

Placental lactogen Prolactin

Progesterone

Chorionic thyrotropin



Sites and mechanisms of hormone

action Hormones act on their specific receptors located

on or within their target cells

1. At cell- membrane receptor

2. At cytoplasmic receptor

3. At nuclear receptor

Hormone

Receptor

Response



At cell membrane receptors A) Through alteration of intracellular cAMP conc.

Hormone

ReceptorAdenyl

cyclase

Mg++

Cyclic 3’,5’- AMP

ATP

• activate enzymes, alters cell permeability, protein synthesis, secretions

Protein kinase A Ca2+ acts as third

messenger

E.g. : Adrenaline, glucagon, TSH,FSH, LH, PTH, Calcitonin, ACTH,

some hypothalamic releasing hormones, vasopressin (V2)



B) Through IP3/DAG Pathway:

Release intracellular Ca2+ and

Activates Protein kinase C

E.g.: Vasopressin (V1) & Oxytocin



C) Direct Transmembrane

activation of tyrosine

protein kinase: Phosphorylation cascade

Regulation of various

enzymes

E.g.: Insulin,

growth hormone, Prolactin

1

2



At cytoplasmic receptors

Penetrates cell membrane

Combines with cytoplasmic

receptor

Exposes DNA molecule forbinding site

Migrates to nucleus and binds

to specific genes

Mediates synthesis of mRNA

and functional proteins

E.g.: glucocorticoids, mineralocorticoids, androgens, Estrogens, progestins,

calcitriol



At nuclear receptor

Penetrates the nucleus

Combines with receptor

Alters DNA-RNA mediated protein synthesis

Nuclear receptor

E.g.: Thyroxine, Triiodothyronine



Anterior Pituitary (Adenohypophysis)

Hormones

Growth Hormone

A 191 amino acid, single chain peptide of MW 22000

Physiological functions Promotes growth of all organs by inducing hyperplasia

Promotes retention of nitrogen and other tissue

constituents

Promotes utilization of fats and spares carbohydrates



GH acts on cell surface JAK-STAT protein kinase

receptors



Indirect actions of GH

Growth promoting

Nitrogen retaining and

Metabolic actions

Are exerted through theelaboration of peptides called

somatomedins or Insulin like

growth factors (mainly IGF-1)

Like insulin, IGF-1 promotes

lipogenesis and glucose uptake

by muscles

(Major source

of IGF-1)



Direct actions of GH

Induce lipolysis in adipose tissue

Glycogenolysis in liver

Decrease glucose utilization by muscles

Opposite

effects to

those of IGF-1

& Insulin



Pathological involvement Excess production of GH –

Gigantism in childhood Acromegaly in adults





Preparations & Use

Primary indication for GH is

Pituitary dwarfism- 0.03-0.07 mg/kg (0.06-0.16 units/kg) i.m. or

s.c. 3 times a week upto the age of 20-25 years

Two forms of human GH produced by recombinant DNAtechnique (rhGH) Somatropin (191AA) and Somatrem (192AA)

are available for clinical use

rhGH can also be used in Turner’s syndrome and in children with

renal failure

It is also approved for AIDS-related wasting: higher dose (0.05-

0.1 mg/kg/day)

Should not be given postoperatively, trauma, cancer and other

critically ill patients



Adverse effects

Pain at injection site and lipodystrophy

Glucose intolerance

Hypothyroidism

Salt and water retention Hand stiffness

Myalgia (Pain in muscle or group of muscles)

Headache

Rise in intracranial pressure can occur in few cases



GH inhibitors

Somatostatin 14 amino acid peptide

Inhibits the secretion of GH, TSH and Prolactin by pituitary

insulin and glucagon by pancreas and almost all GIT secretions

Side effect: steatorrhoea, diarrhoea, hypochlorhydria, dyspepsia

and nausea

Decreased GI mucosal blood flow helps in controlling bleeding

esophageal & peptic ulcer

Antisecretory action is beneficial in pancreatic , biliary orintestinal fistulae

Used as adjuvant in diabetic ketoacidosis

Use in acromegaly is limited due to short duration of action (t1/2 ~

2-3 min)



Octreotide Synthetic Octapeptide 40 times more potent in suppressing GH secretion

Longer acting (t1/2 ~ 90 min)

It is preferred over somatostatin for acromegaly and secretory

diarrhoeas associated with carcinoid, AIDS, cancer chemotherapy or

diabetes

It controls diarrhoea due to suppression of hormones which enhance

intestinal mucosal secretions

Dose: initially 50-100 g s.c.twice daily, increased upto 500 g TDS

Adverse effects: abdominal pain, nausea, steatorrhoea, diarrhoea and gall stones

Octreotide i.v. injection (100 g followed by 25-50 g/hr)- reduces hepatic blood

flow and helps stop esophageal variceal bleeding





Congenital disease due to absence or deficiency of normal

thyroid secretion, characterized by physical deformity,

dwarfism, mental retardation, and often by goiter



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Hormones & Hormones Antagonists