Kalloo N B, Gearhart J P, Barrack E R
Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
J Clin Endocrinol Metab. 1993 Sep;77(3):692-8. doi: 10.1210/jcem.77.3.8370691.
Using immunohistochemistry, we investigated the distribution of androgen receptors (AR) and estrogen receptors (ER) in the external genitalia of human male and female fetuses at 18-22 weeks gestation. In the male, the corpus cavernosum, and the stroma of the inner prepuce, scrotum, and periphery of the glans were AR rich. The corpus spongiosum, a well defined structure that surrounds the penile urethra in the neonate, was not yet developed at this fetal age, but the periurethral mesenchyme (presumably the primordium of the corpus spongiosum) was intensely AR positive. In contrast, the epithelium of the preputial skin, penile shaft skin, and scrotal skin were AR negative. The urethral plate in the distal glans was nonpatent and was filled with a meshwork of AR-negative epithelial cells. Canalization of the AR-negative urethral plate was observed to begin where it joined the patent distal penile urethra, which was AR positive. Male external genitalia lacked ER, ruling out a direct influence of maternal estrogen on male genital development. Interestingly, female external genital structures contained AR, and the distribution of AR and staining intensity were strikingly similar to that in the male. The distribution of AR in the female provides a mechanism to explain how female external genitalia become masculinized if exposed to elevated androgen levels in the first trimester. Moreover, it implies that in the male, these AR indeed mediate androgen-dependent male external genital development. Female fetal external genitalia were also intensely ER positive in the stroma of the labia minora and in the periphery of the glans and inner prepuce. The presence of ER suggests that maternal estrogen may play a direct role in female external genital development, challenging the widely held view that female external genital development is passive because it can occur in the absence of fetal gonadal hormones.
我们采用免疫组织化学方法，研究了妊娠18 - 22周的人类男性和女性胎儿外生殖器中雄激素受体（AR）和雌激素受体（ER）的分布情况。在男性胎儿中，海绵体以及内包皮、阴囊和龟头周边的间质富含AR。海绵体在新生儿期是围绕阴茎尿道的一个明确结构，但在这个胎儿时期尚未发育，不过尿道周围间质（可能是海绵体的原基）AR呈强阳性。相比之下，包皮皮肤、阴茎体皮肤和阴囊皮肤的上皮AR呈阴性。龟头远端的尿道板未贯通，充满了AR阴性的上皮细胞网络。观察到AR阴性的尿道板在与AR阳性的阴茎远端贯通尿道连接处开始贯通。男性外生殖器缺乏ER，排除了母体雌激素对男性生殖器发育的直接影响。有趣的是，女性外生殖器结构含有AR，其AR的分布和染色强度与男性惊人地相似。女性体内AR的分布提供了一种机制，用以解释如果在孕早期暴露于升高的雄激素水平下，女性外生殖器如何变得男性化。此外，这意味着在男性中，这些AR确实介导了雄激素依赖的男性外生殖器发育。女性胎儿外生殖器在小阴唇间质、龟头周边和内包皮中ER也呈强阳性。ER的存在表明母体雌激素可能在女性外生殖器发育中起直接作用，这对广泛持有的观点提出了挑战，即女性外生殖器发育是被动的，因为它可以在没有胎儿性腺激素的情况下发生。
