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 intense biological activity that is produced by specific cells in the body and is transported through circulation to act on its target cells.

Hormones regulate body functions to bring about a programmed pattern of life events and maintain homeostasis 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 main functions: [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 of anterior 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
Receptor

ATP
Adenyl cyclase

Mg++ Cyclic 3,5- AMP

Protein kinase A

Ca2+ acts as third messenger

activate enzymes, alters cell permeability, protein synthesis, secretions

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

At cytoplasmic receptors

Penetrates cell membrane Combines with cytoplasmic receptor Exposes DNA molecule for binding 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 the elaboration of peptides called somatomedins or Insulin like growth factors (mainly IGF-1)

(Major source of IGF-1)

Like insulin, IGF-1 promotes lipogenesis and glucose uptake by muscles

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

Hyposecretion of GH Pituitary dwarfism

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 DNA technique (rhGH) Somatropin (191AA) and Somatrem (192AA) are available for clinical use rhGH can also be used in Turners syndrome and in children with renal failure It is also approved for AIDS-related wasting: higher dose (0.050.1 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 or intestinal 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

Prolactin

Physio-pathological involvement

Hyperprolactinaemia is responsible forgalactorrhoea- amenorrhoea- infertility syndrome

Congenital disease due to absence or deficiency of normal thyroid secretion, characterized by physical deformity, dwarfism, mental retardation, and often by goiter