Endocrine Pharmacology Notes

Endocrine Pharmacology Introduction

Key Areas

• Signalling molecules (hormones, chemical mediators) affecting biological function.
• Key areas:
  • Adrenal steroids
  • Reproductive function and oral contraceptives
  • Thyroid function
  • Insulin and diabetes
• Important hormones: cortisol, oestrogen, thyroxine, insulin.
• Important mediators: purines, histamine, 5-HT, nitric oxide, peptides.

Cell Signalling Basics

• Cells communicate through messengers.
• Messengers: small chemicals, peptides, antibodies, etc. (hormones, mediators, neurotransmitters).
• Hormones: endocrine system messengers from glands to cells.
• Three hormone classes: peptide/protein, steroid (lipid-derived), amino acid (or fatty acid derivatives).

Cell Signalling Processes

• Synthesis of signalling molecule.
• Release of signalling molecule.
• Transport to target cell.
• Detection by specific receptor protein.
• Change in target cell function.
• Inactivation/removal of signalling molecule.

Hormones

• Peptide/protein hormones: Hypothalamic, anterior & posterior pituitary, calcium regulating, and pancreatic hormones.
• Steroid hormones: Adrenal cortical, male & female reproductive hormones, 1,25-dihydroxyvitamin D.
• Amino acid or fatty acid derived hormones: Thyroid, adrenal medullary, cardiovascular hormones, pineal hormones, growth factors/cytokines, and eicosanoids.

Hormone Structures

• Protein & peptide hormones: Prohormones (e.g., Endothelin), Insulin (A and B chains).
• Steroid hormones: Derived from Cholesterol; Steroid Nucleus
• Amino acid hormones: Derived from Tyrosine; examples include Thyroxine and Epinephrine.

Hormone Synthesis & Regulation

• Cholesterol is a precursor to steroid hormones.
• Regulation involves feedback loops (short and long) and trophic hormone signals.

Types of Signalling

• Endocrine: Long-range via bloodstream (e.g., insulin).
• Paracrine: Short-range to nearby cells (e.g., somatostatin, neurotransmission).
• Autocrine: Affects the cell that released the signal (e.g., neurotransmitters, growth factors).

Endocrine Pharmacology & Hormone Release

• Hypothalamus → pituitary gland → hormone release.
• Effects on organs: adrenal gland (cortisol), sex organs (oestrogen), thyroid gland (thyroxine).
• Downstream effects: blood pressure, heart rate, reproductive function.

HPA Axis & Regulation

• Stress: Hypothalamus (CRH) → Pituitary gland (ACTH) → Adrenal gland (Cortisol, Dehydroepiandrosterone, Aldosterone).
• Thyroid System: Hypothalamus (TRH) → Anterior pituitary gland (TSH) → Thyroid gland (T3 and T4).

Insulin and Diabetes

• Insulin: regulates glucose utilisation, affects metabolism & energy balance.
• Diabetes:
  • Type 1: insulin deficiency
  • Type 2: insulin resistance

Mediators

• A substance released from local cells, producing a biological action on target cells.
• Exogenous application reproduces the endogenous effect.
• Interference modulates the endogenous response.
• All hormones are mediators, but not all mediators are hormones.

Mediators Details

• Involved in endocrine, paracrine, autocrine signalling.
• Hormones (e.g., insulin, steroids) are mediators from glands.
• Physiological responses & pharmacological potential.
• Dysfunction can be pathogenic.
• Agonists/antagonists may have clinical benefit.

Chemical Mediators Types

• Gases (e.g., nitric oxide (NO)).
• Amine neurotransmitters (e.g., noradrenaline, 5-HT).
• Hormones (e.g., steroids, angiotensin, insulin).
• Locally released substances (e.g., eicosanoids, histamine).