Role of steroid 5 alpha-reductase activity in sexual differentiation of the guinea pig.
The possible role of 5 alpha-reduction of steroids in the sexual differentiation of guinea pigs was determined by treating pregnant guinea pigs with a 5 alpha-reductase activity (5 alpha RA) inhibitor (17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one, 4MA, 10 mg/day) from day 30 to 55 of gestation. 5 alpha RA 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 micrograms 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 less than 0.05) and greater amounts at the time of the LH surge (p less than 0.05). Regardless of treatment males did not respond to EB.(ABSTRACT TRUNCATED AT 250 WORDS)
Connolly
P B
PB
Department of Physiology, School of Medicine, Oregon Health Sciences University, Portland.
Resko
J A
JA
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000731:Androstanes / Q000494:pharmacology*; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000096:biosynthesis; D005260:Female; D005836:Genitalia, Female / Q000187:drug effects / Q000254:growth & development; D005837:Genitalia, Male / Q000187:drug effects* / Q000254:growth & development; D006168:Guinea Pigs; D008297:Male; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects* / Q000378:metabolism; D012733:Sex Differentiation / Q000187:drug effects*; D013260:Steroids, Heterocyclic / Q000494:pharmacology*; D013739:Testosterone / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D000731:Androstanes; D001378:Azasteroids; D013260:Steroids, Heterocyclic; D013196:Dihydrotestosterone; C051710:L 636028; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase