Acute administration of estrogen suppresses LH secretion without altering GnRH release in ovariectomized rhesus macaques

The pattern of hypothalamic gonadotropin-releasing hormone (GnRH) release was examined during estrogen (E)-induced suppression of plasma luteinizing hormone (LH) in ovariectomized (OVX) rhesus macaques. In Expt. 1, 4 OVX macaques were fitted with a jugular catheter and a push-pull cannula (PPC) directed into the median eminence (ME). Push-pull perfusion (PPP) was initiated 10 h before and continued for 10 h after subcutaneous estradiol benzoate (EB) injection (42 μg/kg b.wt.). In Expt. 2, 4 additional monkeys were subjected to local intrahypothalamic perfusion with estradiol-17β (E₂, 3 μM) for the last 10 h of a 20-h PPP. In Expt. 3, OVX animals were challenged with 5 μg exogenous GnRH 3 h before and 8 h after EB injection to test for changes in altered LH release. Integrated 10-min ME perfusate and intermittent 10- or 60-min peripheral plasma samples were assayed for GnRH and LH by radioimmunoassay and bioassay, respectively. In addition, 2 other OVX macaques that received similar ME-PPC placement were sacrificed 2 days after the completion of a PPP for immunocytochemical labeling of GnRH neurons at the perfusion site. The results show that after EB, hypothalamic GnRH (MBH-GnRH) release remained unaltered while LH levels declined rapidly (Expt. 1). Similarly, intrahypothalamic perfusion of E₂ failed to change the pattern of MBH-GnRH release in any of 4 monkeys (Expt. 2). Conversely, plasma LH release in response to exogenous GnRH was greatly reduced after EB (Expt. 3). Immunocytochemically labeled GnRH-containing nerve fibers and cell bodies were observed adjacent to the site of PPP in the 2 monkeys examined after the completion of 20 h of PPP. Collectively, these data suggest that acute administration of E exerts immediate negative feedback effects at the pituitary through a process that is unrelated to changes in patterns of mediobasal hypothalamic GnRH release.