In the rat, ovarian LHRH receptor content, measured by the binding of [125I]D-Ala6-Pro9-LHRH ([125I]ALHRH) to ovarian membranes, declines during the days preceding the first preovulatory LH surge. The present results show that LHRH receptor content is low during neonatal-infantile days (days 5-15) and increases markedly thereafter to a maximum by day 25. When ovarian membranes from 10-day-old rats were pretreated with MgCl2 to dissociate endogenously bound hormone, LHRH-binding capacity increased to levels similar to those in untreated ovaries from 25-day-old rats. No significant increase was observed in ovaries from the latter group after MgCl2 exposure. Equilibrium association constants were similar (6-8 × 109 M-1) in MgCl2-treated and control ovaries, indicating that the increase in binding was not due to a change in receptor affinity. Pups prevented from suckling for various time intervals (1-24 h) exhibited an increase in available ovarian LHRHbinding sites which was maximal by 4 h. When pups were allowed to suckle subsequent to a 6-h fast, available ovarian LHRH receptors decreased rapidly (1 h). This decline was not due to a local increase in LHRH triggered by a neural reflex in response to suckling and/or stomach distension. Intragastric administration of milk reproduced the decline in available receptors induced by suckling, whereas stomach distension produced by saline was ineffective. Concomitant with the decline in receptors, suckling produced a significant increase in both stomach content and plasma levels of an LHRH-like material. Fractionation of acid milk extracts in Sephadex G-25 yielded two peaks, one in a position similar to that of synthetic LHRH. Milk LHRH purified in a C-18 Sep-Pak column displaced binding of [125I]A-LHRH to ovarian membranes and yielded a parallel binding curve in the LHRH RIA. This milk LHRH also released LH and FSH from pituitaries in vitro and inhibited FSH-induced estradiol and progesterone secretion from granulosa cells in culture in a dose-related manner, comparable to ALHRH. The suckling-induced decrease in available LHRH receptors was prevented by iv administration of a specific LHRH antiserum directed against all 10 amino acids of native LHRH, suggesting that milk LHRH reaches the ovary via the bloodstream. The results indicate that an LHRH-like substance of milk origin binds to LHRH receptors in the pup ovary, thereby controlling receptor availability. In view of the known inhibitory effects of long term exposure to LHRH, it is suggested that infantile ovarian development in the rat is modulated by the mother via milk LHRH.
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