Pregnanolone, a metabolite of progesterone, stimulates LH-RH release: in vitro and in vivo studies.

The effect of 5 beta- and 5 alpha-reduced progestins on luteinizing hormone-releasing hormone (LH-RH) release was examined using either an in vitro superfusion or an in vivo push-pull perfusion (PPP) technique. Ovariectomized rats (at least 6 days post operation: OVX) were implanted subcutaneously in the neck region with a silastic capsule containing 17 beta-estradiol (235 micrograms/ml: E2). Two days afterwards, these OVX + E2 rats were subjected to experimental conditions. Pregnanolone(5 beta-pregnane-3 beta-ol-20-one) at a low concentration of 0.01 ng/ml and an apparent latency of 1 h stimulated in vitro LH-RH release from superfused hypothalamic fragments containing the preoptic-anterior hypothalamic-mediobasal hypothalamic area (POA-AHA-MBH). The stimulatory effect of pregnanolone required estrogen-priming and a pulsatile mode of administration. In addition, the effect appeared quite specific since other closely related steroids such as epipregnanolone, R-5020 and 5 alpha-DHP were ineffective. In OVX + E2 rats bearing a push-pull cannula (PPC) in the hypothalamic area, in vivo infusion of repetitive pulses of pregnanolone through the PPC was also effective, confirming in vivo the stimulatory effect of pregnanolone on LH-RH release obtained from in vitro preparations. In these experiments, the same OVX + E2 rats served both as an experimental animal receiving pulses of pregnanolone and as a control subject when perfused only with medium after a week interval. The basal release rate of LH-RH and the response to pulsatile pregnanolone were variable among animals apparently due to different locations of PPC in the hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)