Screening of Endocrine and Hormonal Drugs

Screening of Endocrine and Hormonal Drugs

1. Definition, scope & rationale

• Endocrine/hormonal drug screening is the systematic experimental evaluation of natural and synthetic hormone agonists, antagonists and modulators using in vitro and in vivo biological models to establish their potency, agonist/antagonist profile and relative activity against a defined reference standard (Vogel 4e Part XIV, pp.3393–3521; SK Gupta Ch.39, pp.569–612)
• The endocrine system is a collection of ductless glands secreting hormones — specialized signalling molecules synthesized, stored and released directly into the bloodstream to act on distant target cells bearing appropriate receptors (SK Gupta Ch.39, p.569)
  • Neural control resides in the hypothalamus, which secretes releasing/inhibitory hormones to the pituitary via the hypothalamic–hypophyseal portal system; the pituitary ("master gland") then governs peripheral glands through an integrated negative-feedback loop (SK Gupta Ch.39, p.569)
• Elucidation of hormone structures enabled synthesis of peptide and steroid agonists and antagonists of diagnostic and therapeutic value; screening models are needed to characterise each new derivative before development (SK Gupta Ch.39, p.569)
• The classical evaluation strategy for any endocrine target is ablate-and-replace: surgically remove the hormone-producing gland (adrenalectomy, ovariectomy, orchiectomy, thyroidectomy, hypophysectomy) then substitute exogenous extract or synthetic hormone and measure the restored end-organ response (Vogel 4e Part XIV, p.3393; SK Gupta Ch.39, pp.594, 598, 605)
• Scope of this topic (experimental methods, not clinical endocrine pharmacotherapy): estrogen/antiestrogen, progestational, androgen/anabolic, thyroid/antithyroid, corticosteroid (gluco- and mineralocorticoid) and oxytocic/uterine-stimulant bioassays; hormone bioassay versus immunoassay; reference-standard principles (Vogel 4e Part XIV; SK Gupta Ch.39)