Activation of estradiol-positive feedback at puberty: Estradiol sensitizes the LHRH-releasing system at two different biochemical steps

Experiments were performed to examine whether estradiol (E₂) can influence some of the intraneuronal mechanisms involved in luteinizing hormone-releasing hormone (LHRH) release during the onset of puberty in the female rat. The capacity of median eminence (ME) nerve terminals to secrete LHRH, as determined by both their basal release of LHRH and by their response to prostaglandin E₂ (PGE₂) in vitro, increased significantly during the juvenile-early peripubertal periods of development (postnatal days 22-34). Ovariectomy (OVX) on day 22 led to a striking reduction in LHRH response to PGE2 on day 34. E₂ administered via s.c. Silastic capsules, at a dose that reproduces juvenile serum E₂ levels, restored the response. Simulation of first proestrous serum E2 levels in late juvenile (28-day-old) female rats enhanced both the sensitivity and the responsivenes of LHRH-containing terminals to PGE₂. Furthermore, E₂ enhanced the sensitivity and the responsiveness of LHRH terminals to norepinephrine (NE). This effect appeared to be related to both the increased LHRH response to PGE₂ and an enhanced sensitivity of the PGE₂-synthesizing pathway to NE. This is because MEs from E2-treated rats showed a marked increase in PGE₂ release in response to a NE concentration which was barely effective in untreated controls. It is suggested that one of the mechanisms by which E₂ activates the first preovulatory discharge of LHRH release in the female rat is by facilitating the occurrence of two different but sequentially related biochemical events: The stimulation of PGE₂ formation by NE and the enhancement of LHRH release by PGE₂. In addition, it appears that maintenance of LHRH responsiveness to PGE₂, which has been implicated as an obligatory component of NE-induced LHRH release, is E₂-dependent.