Ovarian hormone dependence of alpha(1)-adrenoceptor activation of the nitric oxide-cGMP pathway: Relevance for hormonal facilitation of lordosis behavior

The ovarian hormones estradiol (E-2) and progesterone (P) facilitate rat lo rdosis behavior in part by regulating the expression of and signal transduc tion by adrenoceptors in the hypothalamus (HYP) and preoptic area (POA). Th e major adrenoceptor subtype mediating E-2 and P facilitation of lordosis i s the ct, adrenoceptor. In the present studies, we tested the hypotheses th at (1) alpha(1)-adrenoceptors in the HYP enhance lordosis responses by acti vating the nitric oxide (NO)-cGMP signaling pathway, and (2) coupling of al pha(1)-adrenoceptors to this signal transduction pathway is hormone-depende nt. Basal levels of cGMP were significantly higher in HYP and POA slices fr om animals treated with E-2 and P when compared with slices from ovariectom ized controls or females treated with only E-2 or P. When slices of HYP and POA from ovauiectomized female rats were incubated with norepinephrine or the selective alpha(1)-adrenoceptor agonist phenylephrine, cGMP accumulatio n was observed only if slices had been derived from females treated with bo th E-2 and P before experimentation. Moreover, alpha(1)-adrenoceptor stimul ation of cGMP synthesis was blocked by an inhibitor of NO synthase, confirm ing that these receptors act by NO-mediated stimulation of soluble guanylyl cyclase. Behavioral studies demonstrated further that the cell-permeable c GMP analog 8-bromoadenosine-cGMP reverses the inhibitory effects of the alp ha(1)-adrenoceptor antagonist prazosin on lordosis behavior in E-2- and P-t reated female rats. Thus, the NO-cGMP pathway mediates the facilitatory eff ects of alpha(1)-adrenoceptors on lordosis behavior in female rats, and pre vious exposure of the HYP and POA to both E-2 and P are required to link al pha(1)-adrenoceptors to this pathway.