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).