Cunha Gerald R, Place Ned J, Baskin Larry, Conley Alan, Weldele Mary, Cunha Tristan J, Wang Y Z, Cao Mei, Glickman Stephen E
Departments of Anatomy, University of California, San Francisco, CA 94143, USA.
Biol Reprod. 2005 Sep;73(3):554-64. doi: 10.1095/biolreprod.105.041129. Epub 2005 May 25.
Studies were conducted to elucidate the importance of androgen-mediated induction of the extreme masculinization of the external genitalia in female spotted hyenas. Phallic size and shape; androgen receptor (AR) and alpha-actin expression; and sex-specific differences in phallic retractor musculature, erectile tissue, tunica albuginea, and urethra/urogenital sinus were examined in male and female fetuses from Day 30 of gestation to term. Similar outcomes were assessed in fetuses from dams treated with an AR blocker and a 5alpha-reductase inhibitor (antiandrogen treatment). Clitoral and penile development were already advanced at Day 30 of gestation and grossly indistinguishable between male and female fetuses throughout pregnancy. Sex-specific differences in internal phallic organization were evident at Gestational Day 45, coincident with AR expression and testicular differentiation. Antiandrogen treatment inhibited prostatic development in males and effectively feminized internal penile anatomy. We conclude that gross masculinization of phallic size and shape of male and female fetuses is androgen-independent, but that sexual dimorphism of internal phallic structure is dependent on fetal testicular androgens acting via AR in the relevant cells/tissues. Androgens secreted by the maternal ovaries and metabolized by the placenta do not appear to be involved in gross masculinization or in most of the sex differences in internal phallic structure.
开展了多项研究，以阐明雄激素介导的雌性斑鬣狗外生殖器极度雄性化的重要性。在妊娠第30天至足月的雄性和雌性胎儿中，检查了阴茎的大小和形状、雄激素受体（AR）和α-肌动蛋白的表达，以及阴茎退缩肌、勃起组织、白膜和尿道/泌尿生殖窦的性别特异性差异。在用AR阻滞剂和5α-还原酶抑制剂治疗的母鼠所产胎儿（抗雄激素治疗）中评估了类似的结果。在妊娠第30天时，阴蒂和阴茎的发育就已提前，并且在整个孕期中，雄性和雌性胎儿之间的外观没有明显差异。妊娠第45天时，阴茎内部组织的性别特异性差异明显，这与AR表达和睾丸分化同时出现。抗雄激素治疗抑制了雄性前列腺的发育，并有效地使阴茎内部解剖结构雌性化。我们得出结论，雄性和雌性胎儿阴茎大小和形状的总体雄性化与雄激素无关，但阴茎内部结构的性别二态性取决于胎儿睾丸雄激素通过相关细胞/组织中的AR起作用。母体卵巢分泌并经胎盘代谢的雄激素似乎不参与总体雄性化或阴茎内部结构的大多数性别差异。
