Modulation of pituitary gonadotropin-releasing hormone receptors during lactation in the rat.

Lactation is associated with a suppression of pituitary GnRH receptors (GnRH-R), and removal of the suckling stimulus for 24 h causes a 4- to 5-fold increase in GnRH-R. These studies were designed to examine the time course of recovery of GnRH-R after pup removal and to determine the roles that GnRH and PRL may play in modulating GnRH-R during lactation and after pup removal. All studies were performed on day 10 postpartum using ovariectomized rats suckling eight or zero pups. GnRH-R had more than doubled by 8 h after pup removal and had increased 4-5 times 16 h after pup removal to reach levels observed in nonsuckled controls. The increase in GnRH-R after pup removal resulted in a significant increase in pituitary responsiveness to GnRH. Maintenance of hyperprolactinemia after pup removal, by injecting ovine PRL, reduced the increase in GnRH-R by about 50%. Simultaneous administration of GnRH with ovine PRL restored GnRH-R to control levels. Administration of a potent antiserum to GnRH at the time of pup removal completely blocked the up-regulation of GnRH-R 24 h later. In the presence of the suckling stimulus and hyperprolactinemia, administration of pharmacological doses of GnRH caused a complete restoration of GnRH-R to levels observed in nonsuckled controls. Inhibition of suckling-induced PRL secretion with CB-154 caused a 2-fold increase in GnRH-R, and this effect could be completely reversed by simultaneous treatment with ovine PRL. These studies show that the suppression of pituitary GnRH-R during lactation appears to be due primarily to inhibition of GnRH secretion. After pup removal, recovery of GnRH-R occurs very rapidly, with recovery (4- to 5-fold increase) being completed by 16 h. Endogenous GnRH secretion is absolutely necessary for the up-regulation of GnRH-R to occur. The decrease in PRL levels after pup removal contributes to this process, most likely by causing an increase in GnRH secretion.