Progesterone receptor function from a behavioral perspective.

Hormonal induction of sexual receptivity in ovariectomized female mice can be effectively reinstated by sequential administration of estradiol and progesterone. In this regard, mice appear to be similar to other rodents. While it is generally accepted that hypothalamic progesterone receptors function as estradiol-induced transcription factors in the induction of sexual receptivity in rats, hamsters, and guinea pigs, relatively little is known about their role in the mouse, a species which exhibits genotypic and strain differences in the responsiveness to steroid hormones. Using a transgenic mouse carrying a null mutation for the progesterone receptor by gene targeting, we examined the role of the progesterone receptor as a coordinator of key regulatory events in the induction of sexual receptivity. A concordance between hypothalamic progesterone receptor levels and behavioral responsiveness was established by comparing the homozygous mutant, heterozygous mutant, and wild-type littermates. The behavioral and biochemical findings reveal the importance of estradiol-induced progesterone receptors for the expression of sexual behavior in female mice. The behavioral response of the two parental mouse strains from which the recombinant genotype was generated was also examined. As an extension of our earlier studies on the ligand-independent activation of progesterone receptors by neurotransmitters, the behavioral effect of dopamine in the facilitation of sexual receptivity in mice was also examined. The studies provide further evidence that steroid hormone receptors function as general transcription factors to achieve the integration of neural information in the central nervous system, and they assign a more important role for progesterone receptors than hitherto envisioned.