Role of Steroid 5α-Reductase Activity in Sexual Differentiation of the Guinea Pig

Publisher Website
Google Scholar
Abstract
The possible role of 5α-reduction of steroids in the sexual differentiation of guinea pigs was determined by treating pregnant guinea pigs with a 5α-reductase activity (5αRA) inhibitor (17β-N, N-diethylcarbamoyl-4-methyl-4-aza-5α-androstan-3-one, 4MA, 10 mg/day) from day 30 to 55 of gestation. 5αRA in fetal diencephalon tissue obtained from 4MA-treated mothers on day 55 of gestation was suppressed compared to that of control tissue. Four litters receiving 4MA were carried to term along with an equal number of litters receiving the vehicle alone. Males that received 4MA in utero (n = 6) had altered external genitalia, i.e., hypospadias and reduced anogenital distances, but their adult copulatory behavior did not differ from that of controls (n = 7). In order to evaluate treatment effects on the hypothalamic-pituitary axis, all animals were challenged with estradiol benzoate (EB, 10 µg in oil, s.c.) 2 weeks after gonadectomy. Serial plasma samples were obtained and analyzed for luteinizing hormone (LH) using an heterologous radioimmunoassay. Control females (n= 13) and 4MA-treated females (n = 5) released LH in surge quantities about 42 h after EB treatment. Plasma from 4MA-treated females differed from controls in that it contained greater overall quantities of LH (p < 0.05) and greater amounts at the time of the LH surge (p < 0.05). Regardless of treatment males did not respond to EB. However, 4MA-treatment appeared to blunt the post-castration rise in LH since control plasma (n = 7) contained significantly more LH (p < 0.05) compared to plasma obtained from 4MA-treated animals (n = 6). These data suggest that 5α-reduction of testosterone is not required for androgenization of the male brain but is needed for normal development of external genitalia. The data also suggest that 5α-reduced steroids exert developmental effects on female fetuses since inhibition of 5αRA in fetal life renders them more responsive to the positive feedback action of EB.