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The Journal of Neuroscience, November 15, 1998, 18(22):9556-9563

Induction of Progestin Receptors by Estradiol in the Forebrain of Estrogen Receptor- Gene-Disrupted Mice

C. A. Moffatt¹, E. F. Rissman², M. A. Shupnik³, and J. D. Blaustein¹

¹ Neuroscience and Behavior Program and Center for Neuroendocrine Studies, University of Massachusetts, Amherst, Massachusetts 01003, and Departments of ² Biology and ³ Internal Medicine, University of Virginia, Charlottesville, Virginia 22903

Mice, rats, and humans have two types of estrogen receptors, estrogen receptor- (ER) and estrogen receptor- (ER). Estrogen receptor- gene-disrupted (ER-disrupted) mice bear two nonfunctional copies of the ER gene. This mutation blocks the synthesis of full-length ER, renders the animals infertile, and inhibits the induction of female sexual behaviors by estradiol and progesterone. It is likely that many of the processes contributing to the regulation of sexual receptivity by estradiol and progesterone are compromised in ER-disrupted mice. However, given the importance of progesterone in the regulation of sexual receptivity and given the importance of progestin receptors (PRs) in mediating the responses of females to progesterone, we investigated the effects of ER disruption on the induction of PRs by estradiol in the forebrain.

We hypothesized that estradiol would induce PRs in wild-type mice but not in ER-disrupted mice. Ovariectomized wild-type and ER-disrupted mice were implanted with either estradiol-filled capsules or empty capsules for 5 d, after which their brains were processed for the immunocytochemical detection of PR. Estradiol increased the number of PR-immunoreactive cells in both wild-type and ER-disrupted mice. The residual responsiveness of ER-disrupted mice to estradiol could be accounted for by an ER-dependent mechanism or another as yet unidentified estrogen receptor; however, because ER-immunoreactivity and PCR product representing the 3' end of ER mRNA were found in at least one PR-containing region of the ER-disrupted mice, an ER splice variant may also mediate the induction of PR-immunoreactivity in ER-disrupted mice.

Key words: estrogen receptors; progestin receptors; ventromedial hypothalamus; ovariectomy; estradiol; progesterone

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18229556-08$05.00/0

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