Gonadotrope Responsiveness to GnRH

Viewed mechanistically, a 50% reduction in incremental (peak minus nadir) LH pulse amplitude in aging men could denote a diminished amount of hypothalamic GnRH secreted per burst, an abnormal GnRH waveform, and/or impaired gonadotrope-cell responsiveness to GnRH. Recent GnRH dose-response analyses conducted in randomly assigned order on separate days establish normal maximal and enhanced submaximal acute and short-term (14-d) stimulatory effects of GnRH in the elderly male (28,96,97). Heightened sensitivity to small GnRH amounts would occur predictably in the presence of augmented pituitary LH stores in older individuals, as inferred postmortem (24). A preliminary report indicates that pituitary sensitivity to submaximal GnRH stimulation is accentuated further by short-term androgen depletion in aged volunteers (98). If confirmed, the latter insight would indicate that lower bioavailable testosterone concentrations in older men cause or potentiate disproportionate LH release induced by a submaximal GnRH stimulus.

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