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 sucklinginduced 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 GnRHR 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.
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