Bentvelsen F M, Brinkmann A O, van der Schoot P, van der Linden J E, van der Kwast T H, Boersma W J, Schröder F H, Nijman J M
Department of Pediatric Urology, Erasmus University, Rotterdam, The Netherlands.
Mol Cell Endocrinol. 1995 Sep 22;113(2):245-53. doi: 10.1016/0303-7207(95)03593-v.
Distribution and regulation of androgen receptor expression during fetal and neonatal virilization of the rat fetus was assessed by immunohistochemistry. In mesonephric duct derivatives the androgen receptor expression became evident first in the efferent ductules and epididymis (on fetal day 14), subsequently in the vas deferens and finally in the seminal vesicle. Mesenchymal cells of the urogenital tubercle were positive for androgen receptors from fetal day 14 onwards. In the mesenchymal cells of the prostate anlagen, androgen receptor positive cells were found first on fetal day 16. Administration of 5alpha-dihydrotestosterone to pregnant rats from day 11 to day 20 of gestation caused a stabilization of the wolffian duct in female fetuses. The androgen receptor expression pattern became similar as found in mail fetuses, and showed an increase in density and in frequency of androgen receptor positive cells. Administration of the androgen antagonist flutamide during the same interval caused a reduction in density and frequency of androgen receptor positive cells in male fetuses. These findings indicate that androgens enhance the expression of androgen receptors in the developing rat genital tract by induction of androgen receptor positive cells, and by increasing the frequency. The developmental pattern of androgen receptor expression in the rat mesonephric duct system reflects the androgen-responsiveness of the ducts, and is consistent with induction of the androgen receptor along the ducts by testosterone reaching these structures in an exocrine fashion.
通过免疫组织化学评估大鼠胎儿在胎儿期和新生儿期男性化过程中雄激素受体表达的分布和调节。在中肾管衍生物中,雄激素受体表达首先在输出小管和附睾中明显出现(在胎儿第14天),随后在输精管中出现,最后在精囊中出现。从胎儿第14天起,泌尿生殖结节的间充质细胞雄激素受体呈阳性。在前列腺原基的间充质细胞中,在胎儿第16天首次发现雄激素受体阳性细胞。在妊娠第11天至第20天给怀孕大鼠施用5α-二氢睾酮可使雌性胎儿的中肾管稳定。雄激素受体表达模式变得与雄性胎儿相似,并显示雄激素受体阳性细胞的密度和频率增加。在相同时间段内施用雄激素拮抗剂氟他胺会导致雄性胎儿中雄激素受体阳性细胞的密度和频率降低。这些发现表明,雄激素通过诱导雄激素受体阳性细胞并增加频率来增强发育中大鼠生殖道中雄激素受体的表达。大鼠中肾管系统中雄激素受体表达的发育模式反映了导管的雄激素反应性,并且与睾酮以外分泌方式到达这些结构后沿导管诱导雄激素受体一致。