Prolactin release in response to blockade of dopaminergic receptors and to TRH injection in developing and adult rats: Role of estrogen in determining sex differences

Female rats released more prolactin in response to blockade of dopaminergic receptors with Pimozide (P) than males at all ages studied (from day 15 to day 75). Testosterone propionate (Tp) administered during the neonatal period did not change the female response to P. The male response to P was not facilitated by neonatal orchidectomy, orchidectomy at day 21 or “feminization” of male fetuses, but it was enhanced by an injection of estradiol benzoate (Eb; 5 μg, SC, 48 h before P). Ovariectomy of adult androgenized or normal female rats blunted the prolactin response to P and an estrogen injection facilitated it. Pituitary prolactin reserve was evaluated by injecting TRH and measuring the resulting plasma prolactin levels. Adult males released less prolactin in response to TRH than females on proestrus or on diestrus day 1. The response of adult females to TRH varied during the cycle, being maximal on proestrus and minimal on diestrus day 2. In both sexes, castration suppressed the prolactin response to TRH and a single Eb injection restored it. Pituitary prolactin content was lower in males than in females and decreased following castration in both sexes. Eb partially restored it. The results indicate that a) the prolactin response to blockade of DA receptors is more pronounced in females than in males, b) this difference is not determined by a process of neonatal or fetal hypothalamic sexual differentiation, but rather is a consequence of a modulating action of estrogen at the hypothalamichypophyseal level during the course of sexual development, and c) the main site of action of estrogen in determining this sex difference appears to be the pituitary gland.