Department of Population Medicine & Diagnostic Sciences, Cornell University, Ithaca, NY 14853, USA.
Gen Comp Endocrinol. 2011 Feb 1;170(3):455-9. doi: 10.1016/j.ygcen.2010.10.016. Epub 2010 Oct 29.
The androgen receptor blocker flutamide and the 5α-reductase inhibitor finasteride have been used in a variety of species to investigate the ontogeny of sexual dimorphisms by treating pregnant females or neonates at critical periods of sexual differentiation. Likewise, we have used these drugs to study the profound masculinization of the external genitalia in female spotted hyenas. However, a potential pitfall of administering flutamide, either alone or in combination with finasteride, is that it maintains or even raises plasma concentrations of luteinizing hormone (LH) and testosterone (T), because negative feedback of the hypothalamic-pituitary-gonadal axis is disrupted. Contrary to expectations, when pregnant spotted hyenas were treated with flutamide and finasteride (F&F), the concentrations of T during late gestation were suppressed relative to values in untreated dams. Herein, we further investigate the paradoxical effects of F&F treatment on a battery of sex hormones in spotted hyenas. Beyond the effects on T, we found plasma concentrations of LH, estradiol, progesterone and androstenedione (A4) were also significantly lower in F&F-treated pregnant hyenas than in controls. Flutamide and finasteride did not have similar effects on LH, T, and A4 concentrations in male hyenas. The paradoxical effect of F&F treatment on LH and T concentrations in the maternal circulation suggests that negative feedback control of gonadotropin and androgen secretion may be modified in spotted hyenas during pregnancy.
雄激素受体阻滞剂氟他胺和 5α-还原酶抑制剂非那雄胺已被用于多种物种，通过在性分化的关键时期对怀孕的雌性或新生动物进行治疗，以研究性二态性的发生。同样，我们也使用这些药物来研究雌性斑点鬣狗外生殖器的显著雄性化。然而，单独或联合使用氟他胺和非那雄胺存在一个潜在的陷阱，即它会维持甚至提高促黄体生成素（LH）和睾酮（T）的血浆浓度，因为下丘脑-垂体-性腺轴的负反馈被破坏。出乎意料的是，当怀孕的斑点鬣狗接受氟他胺和非那雄胺（F&F）治疗时，与未治疗的母鬣狗相比，妊娠晚期 T 的浓度受到抑制。在此，我们进一步研究了 F&F 处理对斑点鬣狗一系列性激素的矛盾影响。除了对 T 的影响外，我们还发现 F&F 处理的怀孕鬣狗的血浆 LH、雌二醇、孕酮和雄烯二酮（A4）浓度也明显低于对照组。氟他胺和非那雄胺对雄性鬣狗的 LH、T 和 A4 浓度没有类似的影响。F&F 处理对母血循环中 LH 和 T 浓度的矛盾影响表明，在怀孕期间，斑点鬣狗的促性腺激素和雄激素分泌的负反馈控制可能会发生改变。
