Sir T
Departamento de Medicina, Facultad de Medicina, Universidad de Chile, Santiago de Chile.
Rev Med Chil. 1997 Jun;125(6):710-8.
In hyperandrogenic states an abnormal pattern of LH secretion in women is observed, which is presumed to result from a direct action of androgen or its conversion to estrogen. Two strategies are available to study the effect of testosterone on LH secretion. One involves the use of non-steroidal compounds that block the negative feedback actions of endogenous androgens by binding to androgen receptors; the other consists only in the administration of androgens. Following these two strategies, we first studied the pulsatile gonadotrophin secretion in hyperandrogenic women, following flutamide administration, a specific androgen receptor blocker. Flutamide treatment was followed by a decrease in LH pulse amplitude and mean LH concentrations, demonstrating that androgen receptor blockade reduces LH secretion in hyperandrogenic women. To establish the level at which the androgen effect is exerted, we further studied the acute effect of testosterone (hyperandrogenic levels) and the blockade of its receptor on LH secretion in patients with severe hypothalamic deficiency treated with pulsatile GnRH (GnRHp). LH pulse profiles were assessed under GnRHp treatment alone, during testosterone and during testosterone and flutamide administration. Testosterone increased LH secretion and LH pulse amplitude. Flutamide significantly reverted the LH increase induced by testosterone. These results strongly suggest that testosterone in the hyperandrogenic female range, may facilitate LH secretion by the pituitary, effect that is reversed by the blockade of the androgen receptor.
在高雄激素状态下,女性会出现异常的促黄体生成素(LH)分泌模式,据推测这是雄激素直接作用或其转化为雌激素所致。有两种策略可用于研究睾酮对LH分泌的影响。一种是使用非甾体化合物,通过与雄激素受体结合来阻断内源性雄激素的负反馈作用;另一种仅包括给予雄激素。按照这两种策略,我们首先研究了在给予氟他胺(一种特异性雄激素受体阻滞剂)后高雄激素女性的促性腺激素脉冲式分泌情况。氟他胺治疗后,LH脉冲幅度和LH平均浓度降低,表明雄激素受体阻断可减少高雄激素女性的LH分泌。为确定雄激素发挥作用的水平,我们进一步研究了睾酮(高雄激素水平)及其受体阻断对接受脉冲式促性腺激素释放激素(GnRHp)治疗的严重下丘脑功能减退患者LH分泌的急性影响。在单独使用GnRHp治疗期间、给予睾酮期间以及给予睾酮和氟他胺期间评估LH脉冲情况。睾酮增加了LH分泌和LH脉冲幅度。氟他胺显著逆转了睾酮诱导的LH增加。这些结果强烈表明,高雄激素女性范围内的睾酮可能促进垂体分泌LH,而雄激素受体阻断可逆转这种作用。