STEROIDAL REGULATION OF BIOLOGICALLY-ACTIVE LUTEINIZING-HORMONE SECRETION IN MEN AND WOMEN

The biological activity of circulating luteinizing hormone (LH) molecu les can be assessed with high sensitivity, specificity, and precision by the in-vitro rat interstitial (Leydig)-cell testosterone (RICT) bio assay. Compared to immunoreactive estimates of the LH content of plasm a, the living Leydig-cell bioassay integrates the functional in-vitro potency of all circulating LH isoforms, while simultaneously reflectin g the effects of otherwise potentially confounding in-vivo antagonists of LH action on steroidogenesis. Here, we review the pathophysiologic al regulation by steroid hormones of bioactive LH secretion and cleara nce in men and women. Our investigations and those in the available li terature indicate that: (i) exogenous (non-aromatizable) 5-alpha-dihyd rotestosterone infusion suppresses LH bioactivity, whereas blockade of the endogenous androgen receptor with flutamide increases secretion o f biopotent LH in men; (ii) endogenous androgen excess due to a mascul inizing testosterone-secreting adrenal tumour in a post-menopausal wom an reversibly suppressed plasma LH bioactivity markedly; (iii) exogeno us oestradiol infusion will reduce whereas the antioestrogen, tamoxife n-HCI, can increase bioactive LH secretion in young men; (iv) the effe ct of anti-oestrogen is blunted in healthy older men; (v) endogenous h yperoestrogenism due to an adrenal oestrogen-secreting tumour in a mid dle-aged man with gynaecomastia profoundly but reversibly inhibited bi oactive LH secretion; (vi) in post-menopausal women, exogenous oestrog en administration, whether oral (diethylstilbestrol), percutaneous (oe stradiol), or intravaginal (oestradiol-impregnated silastic ring), exe rts a temporally biphasic effect on basal bioactive LH secretion, i.e. acute suppression (within 24 h), subacute escape (at 5 - 10 days), an d longer-term inhibition (30 days); (vii) during the normal menstrual cycle, bioactive LH secretion is pulsatile and both frequency, and amp litude regulated; and (viii) oestrogen exposure can enhance gonadotrop hin releasing hormone (GnRH)'s stimulatory action on biologically acti ve LH secretion, resulting in so-called GnRH self-priming. Oestrogen's facilitative effects are achieved by a novel mechanism, in which oest rogen augments LH secretory burst mass and duration. Moreover, GnRH do se-LH secretory response studies show that oestrogen promotes an incre ase in GnRH efficacy (maximal effects) but not GnRH sensitivity (poten cy or half-maximally effective doses of GnRH). We conclude that steroi d hormones are primary regulators of physiologically pulsatile bioacti ve LH secretion in healthy men and women. Moreover, steroids exert pot ent pathological effects on biologically active LH release in conditio ns of selective hyperandrogenism or hyperoestrogenism due to steroid-s ecreting adrenal or gonadal tumours.