PROGESTERONE-RECEPTOR FUNCTION FROM A BEHAVIORAL-PERSPECTIVE

Hormonal induction of sexual receptivity in ovariectomized female mice can be effectively reinstated by sequential administration of estradi ol and progesterone. In this regard, mice appear to be similar to othe r rodents. While it is generally accepted that hypothalamic progestero ne receptors function as estradiol-induced transcription factors in th e induction of sexual receptivity in rats, hamsters, and guinea pigs, relatively little is known about their role in the mouse, a species wh ich exhibits genotypic and strain differences in the responsiveness to steroid hormones. Using a transgenic mouse carrying a null mutation f or the progesterone receptor by gene targeting, we examined the role o f the progesterone receptor as a coordinator of key regulatory events in the induction of sexual receptivity. A concordance between hypothal amic progesterone receptor levels and behavioral responsiveness was es tablished by comparing the homozygous mutant, heterozygous mutant, and wildtype littermates. The behavioral and biochemical findings reveal the importance of estradiol-induced progesterone receptors for the exp ression 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 o n the ligand-independent activation of progesterone receptors by neuro transmitters, the behavioral effect of dopamine in the facilitation of sexual receptivity in mice was also examined. The studies provide fur ther evidence that steroid hormone receptors function as general trans cription factors to achieve the integration of neural information in t he central nervous system, and they assign a more important role for p rogesterone receptors than hitherto envisioned. (C) 1997 Academic Pres s.