Sex-specific postnatal development of negative oestrogen feedback in rats

Experiments were performed in immature and adult male and female rats to study the postnatal development of the negative oestrogen feedback in males and to investigate the mechanisms underlying this development. The following results were obtained: 1. Immature male and neonatally androgenized female rats were less responsive to the LH-inhibiting effect of oestradiol benzoate (OB) than untreated females. In contrast, long-term castrated adult males and females with the androgen-induced persistent oestrus syndrome were distinctively more sensitive than cyclic females to the negative feedback action of oestrogen. 2. The low oestrogen sensitivity in prepubertal males is probably caused by the testicular androgen secretion during the perinatal critical differentiation phase, because after neonatal castration, the LH response to OB injected at 21 days of age did not differ between both sexes. 3. As opposed to the peripubertal desensitization to the negative feedback action of testosterone, the sensitivity to the inhibitory effect of oestrogen on LH secretion did not decrease in males at the time of puberty. 4. Whereas former studies have shown that implantation of OB in the medial preoptic area results in significant reduction of the oestrogen sensitivity in female rats, medial preoptic implants containing oestradiol, testosterone or 5 alpha-dihydrotestosterone did not diminish the LH-suppressing effect of s.c. injected OB in males. The results suggest that 1. a marked sex difference exists in the postnatal development of the negative oestrogen feedback in rats. 2. Higher oestrogen sensitivity in adult male as compared to adult female rats may depend, at least partly, on prepubertal and cyclic desensitization of the negative oestrogen feedback in females and more or less constant sensitivity in males from infancy to adulthood. 3. In males the oestrogen sensitivity seems to be settled for long by the testicular androgen secretion during the perinatal critical differentiation phase. 4. The prepubertal increase of gonadotrophin secretion necessary for the induction of male puberty may mainly be caused by diminution of the gonadotrophin-inhibiting effect of androgens and by the decline of testicular release of inhibin. 5. The oestrogen-induced desensitization of the negative oestrogen feedback mediated by the medial preoptic area is probably a sex-specific mechanism that is only operative in female rats.