Role of prolactin in the regulation of sensitivity of the hypothalamic-pituitary system to steroid feedback.

During sexual maturation, pituitary gonadotropins stimulate the gonads to produce increasing amounts of biologically active steroids and yet gonadotropin release does not become suppressed until concentrations of sex hormones, LH and FSH, in peripheral circulation stabilizes at a higher adult level. There is a substantial amount of evidence that in many mammals, this transition from prepubertal to adult level of activity of the pituitary-gonadal axis is associated with a reduction in the sensitivity of the hypothalamic-adenohypophyseal system to negative feedback of gonadal steroids. In the female, these changes are accompanied by the appearance of positive estrogen feedback on gonadotropin release. In seasonal breeders, annual transitions between the periods of gonadal activity and quiescence are associated with corresponding shifts in the sensitivity to steroid feedback. Peripheral levels of pituitary prolactin (PRL) typically increase during sexual maturation and exhibit large seasonal fluctuations in response to changes in photoperiod and ambient temperature. We propose that PRL is one of the factors which regulate the sensitivity of gonadotropin release to gonadal steroid feedback. In hyperprolactinemic women, responsiveness to negative estrogen feedback increases, while LH response to positive estrogen feedback is reduced or absent. In hyperprolactinemic men, both LH and testosterone levels are reduced, implying increased sensitivity of LH release to negative testosterone feedback. In the male rat, both physiological amounts of PRL and experimentally-induced hyperprolactinemia increase the ability of exogenous testosterone to suppress LH and FSH release. Different regulatory mechanisms appear to operate in the seasonally breeding male golden hamster, in which short photoperiod causes concomitant suppression of PRL, LH, FSH and testosterone release. In this species, pharmacologic suppression of PRL release leads to increased responsiveness of plasma gonadotropin levels to negative feedback effects of testosterone, while PRL-secreting ectopic pituitary transplants exert an opposite effect. We have examined some of the suspected mechanisms of PRL modulation of testosterone feedback in male golden hamsters. In immature animals, the amount of cytoplasmic androgen receptors in the anterior pituitary was decreased by mild hyperprolactinemia and increased by treatment with bromocriptine, an inhibitor of PRL release. Bromocriptine increased pituitary androgen binding also in adult hamsters. These findings would imply that PRL modulates the responsiveness to negative steroid feedback at the pituitary level.(ABSTRACT TRUNCATED AT 400 WORDS)