A membrane-associated progesterone-binding protein, 25-Dx, is regulated byprogesterone in brain regions involved in female reproductive behaviors

The ventromedial hypothalamus (VMH) plays a central role in the regulation of the female reproductive behavior lordosis, a behavior dependent upon the sequential activation of receptors for the ovarian steroid hormones estrad iol (E) and progesterone (P). These receptors function as transcription fac tors to alter the expression of target genes. To discover behaviorally rele vant genes targeted by E and P in the VMH. we used the differential display PCR to identify messenger RNAs that are differentially expressed in the hy pothalamus of ovariectomized (ovx) rats treated with E alone compared with ovariectomized rats treated with E and P. We show here that one interesting mRNA within the hypothalamus that is repressed by P after E priming encode s the protein 25-Dx, the rat homolog of the human membrane-associated P-bin ding protein Hpr6.6. Neurons in the brain containing the highest levels of 25-Dx are located in several nuclei of the basal forebrain, including the V MH. 25-Dx expression is also higher in the hypothalamus of female P recepto r "knockout" mice than in their wild-type littermates. These findings sugge st a mechanism in which the activation of nuclear P receptor represses expr ession of a membrane P receptor. 25-Dx, during lordosis facilitation.