Chronic elevation of estradiol in young ovariectomized rats causes aging-like loss of steroid-induced luteinizing hormone surges

This study was designed to test the hypothesis that the loss of LH surges in response to the stimulatory actions of estradiol and progesterone in middle-aged, persistent-estrous (PE) rats may be caused by chronic elevations in circulating estradiol. Five groups of regularly cycling young rats received an s.c. es-tradiol implant immediately after ovariectomy (Day 0). For de-termination of LH surges, blood samples were collected hourly between 1200–1900 h from each of the five groups at one of the following times: 3 days, or 1, 2, 4, or 8 wk later. On the next day, either progesterone (0.5 mg/100 g BW) or corn oil was injected s.c. at 1200 h, and samples were obtained as be-fore. Incidence and amplitude of estradiol-induced LH surges decreased during the first 2 wk of estradiol treatment, after which no surges occurred. Progesterone enhanced the incidence and amplitude of estradiol-induced LH surges thus delaying their disappearance. These results support our hypothesis and dem-onstrate that the stimulatory actions of estradiol and progester-one on the LH surge sequentially diminish with time after ex-posure to estradiol in young rats. Thus, young rats chronically treated with estradiol may be a useful model for studying the mechanisms whereby LH surges are abolished in middle age dur-ing the hyperestrogenic state of PE. aging, estradiol, LH surges, progesteron