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The ovarian hormones estradiol (E2) and progesterone (P) facilitate rat lordosis behavior in part by regulating the expression of and signal transduction by adrenoceptors in the hypothalamus (HYP) and preoptic area (POA). The major adrenoceptor subtype mediating E2 and P facilitation of lordosis is the α1-adrenoceptor. In the present studies, we tested the hypotheses that (1) α1-adrenoceptors in the HYP enhance lordosis responses by activating the nitric oxide (NO)–cGMP signaling pathway, and (2) coupling of α1-adrenoceptors to this signal transduction pathway is hormone-dependent. Basal levels of cGMP were significantly higher in HYP and POA slices from animals treated with E2 and P when compared with slices from ovariectomized controls or females treated with only E2 or P. When slices of HYP and POA from ovariectomized female rats were incubated with norepinephrine or the selective α1-adrenoceptor agonist phenylephrine, cGMP accumulation was observed only if slices had been derived from females treated with both E2 and P before experimentation. Moreover, α1-adrenoceptor stimulation of cGMP synthesis was blocked by an inhibitor of NO synthase, confirming that these receptors act by NO-mediated stimulation of soluble guanylyl cyclase. Behavioral studies demonstrated further that the cell-permeable cGMP analog 8-bromoadenosine-cGMP reverses the inhibitory effects of the α1-adrenoceptor antagonist prazosin on lordosis behavior in E2- and P-treated female rats. Thus, the NO–cGMP pathway mediates the facilitatory effects of α1-adrenoceptors on lordosis behavior in female rats, and previous exposure of the HYP and POA to both E2 and P are required to link α1-adrenoceptors to this pathway.

the journal of neuroscience/the journal of neuroscience

Ovarian Hormone Dependence of α<sub>1</sub>-Adrenoceptor Activation of the Nitric Oxide–cGMP Pathway: Relevance for Hormonal Facilitation of Lordosis Behavior

Ovarian Hormone Dependence of α1-Adrenoceptor Activation of the Nitric Oxide–cGMP Pathway: Relevance for Hormonal Facilitation of Lordosis Behavior

Ovarian Hormone Dependence of α₁-Adrenoceptor Activation of the Nitric Oxide–cGMP Pathway: Relevance for Hormonal Facilitation of Lordosis Behavior