Absence of Gonadotropin Surges and Gonadotropin-Releasing Hormone Self-Priming in Ovariectomized (OVX), Estrogen (E2)-Treated, Progesterone Receptor Knockout (PRKO) Mice*

作者：Patrick Everett Chappell, Johanna S. Schneider, Pauline Kim, Ming Xu, John P. Lydon, Bert W. O’Malley, Jon E. Levine · 发表于：Endocrinology · 年份：1999 · DOI：10.1210/endo.140.8.6895 · 被引用次数：168 · 研究领域：Estrogen and related hormone effects、Ovarian function and disorders、Hypothalamic control of reproductive hormones

It is well known that estrogen (E2) stimulates expression of progesterone receptors (PRs), thereby inducing responsiveness of several tissues to the actions of progesterone (P). Recent studies have also suggested, however, that biological actions previously ascribed to E2 alone may also be mediated by activation of E2-induced PRs, even independently of signal changes in P concentrations. In the present experiments, the progesterone receptor knockout (PRKO) mice were used to assess the role of PR activation in the positive feedback actions of E2 on gonadotropin release. Ovariectomized (OVX) PRKO mice were tested for their capacity to mount primary gonadotropin surges in response to exogenous E2, and to exhibit a GnRH self-priming effect in response to sequential injections of the decapeptide. Wild-type (WT) and PRKO mice were OVX, treated with both 17beta-estradiol and estradiol benzoate (EB), and then killed at 1900 h on day 7 postOVX. Plasma LH RIA revealed that WT mice exhibited surges in response to the E2 treatment; the PRKO mice, however, showed no elevation in plasma LH above untreated controls. Instead, plasma LH levels in E2-treated, OVX PRKO mice decreased significantly in comparison to untreated OVX PRKO mice, suggesting that E2 can exert a negative feedback influence on LH release in PRKO mice, despite the absence of positive feedback effects. A slight but significant rise in plasma FSH was observed in E2-treated OVX WT mice in comparison to untreated controls: an ...