Sex hormone-dependent brain maturation and sexual behaviour in rats

Abstract

In male and female rats the endogenous steroid and gonadotrophin secretion was inhibited by injecting high doses of chlormadinone acetate (CmAc) from day 14 to 24 of life, i. e. during the period of brain maturation. In adulthood the males treated prepubertally with CmAc exhibited reduced sexual activity and fertility, whereas the females did not differ from the controls. More complete sex hormone deficiency during brain maturation was achieved by castration on day 14 of life. Controls were castrated at normal puberty time (40--60 days). Both groups were then substituted with androgens or oestrogens. In the females castrated on day 14 no impairment of sexual behaviour was observed as compared to the later castrated controls. In contrast, the early castrated males showed delayed onset of mounting behaviour. At autopsy, the weights of their sex organs were found to be lower than in the controls despite equal testosterone replacement for several months. These findings speak in favour of a permanently diminished responsiveness to androgens in males having been exposed to more or less severe androgen deficiency during sex specific brain maturation. Hence, the maturation of a male hypothalamus as well as the differentiation appears to depend at least in part on the presence of androgens, whereas in females it runs without hormonal influence.

PIP: Sex hormone-dependent brain maturation and sexual behavior in rats was studied in animals castrated at an early age and in animals treated with an antigonadotropic and antiandrogenic drug. 30 male and 25 female rats were treated with 6 mg chlormadinone acetate (CMA) from Days 14 to 24 of life. Male and female sexual behavior was tested. In adulthood these treated males were stimulated with 5 IU of follicle stimulating hormone plus 30 IU human chorionic gonadotropin daily and sexual behavior observed. Males treated with CMA exhibited reduced sexual activity and fertility, whereas females were similar in response to controls. In a 2nd experiment, males and females were castrated on Day 14 of life. Other animals were castrated at the start of sexual activity. Both groups then received androgens or estrogens. Sexual behavior was again tested. In females castrated by Day 14, sexual behavior was unimpaired as compared with the older castrates. However, early castrated males showed delayed onset of mounting and ejaculatory behavior after beginning androgen replacement. The reduced mounting frequency and ejaculatory behavior were permanently observed during 2-4 months of hormone replacement. At autopsy the weights of the sex organs were lower than controls despite equal testosterone regimen. In males exposed to severe androgen deficiency during sex-specific brain maturation there is a permanently diminished responsiveness. Female maturation occurs without hormonal influence.