Neonatal progesterone and feminine sexual development

IT has been generally concluded that the inherent programme of sexual differentiation in both sexes of mammals is female. If androgens are present during the critical periods of sexual differentiation, then both genetic males and females will be organised for masculine reproductive organs 1 , hepatic steroidogenic enzymes 2 , hypothalamic control of gonadotropin secretion (tonic) 3 and sexual behaviour 4 ; whereas an absence of either gonad during the critical developmental periods allows for the expression of the inborn female programme 1–3,5 . These results have led to the generally held concept that feminine differentiation requires no hormonal imprinting and will occur normally as long as androgens are not present during the critical periods of sexual embryogenesis. We have reported, however, that interference with perinatal pituitary or adrenal function in female rats causes defects in normal pubertal feminine development which suggests that endogenous hormones may be essential for feminine organisation 6 . Unlike oestradiol and testosterone which both masculinise the female rat 7 , progesterone treatment antagonises these effects and protects the developing female from exogenous oestrogens and androgens 8 . In fact, serum progesterone levels in the foetal monkey have been shown to be significantly higher in the female than in the male 9 and we have recently postulated that perinatal progesterone may be required for feminine neural differentiation 10 . We present here evidence demonstrating that neonatal female rats have a markedly higher level of serum and adrenal progesterone than do neonatal males, and since serum progesterone levels can be further increased by exogenous gonadotropins–adrenal (progesterone) axis may be required for normal feminine sexual differentiation.