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The Journal of Neuroscience, August 15, 1999, 19(16):7191-7197

Ovarian Hormone Dependence of ₁-Adrenoceptor Activation of the Nitric Oxide-cGMP Pathway: Relevance for Hormonal Facilitation of Lordosis Behavior

Hsiao-Pai Chu¹ and Anne M. Etgen^{1, 2}

Departments of ¹ Neuroscience and ² Psychiatry, Albert Einstein College of Medicine, Bronx, New York 10461

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 ₁-adrenoceptor. In the present studies, we tested the hypotheses that (1) ₁-adrenoceptors in the HYP enhance lordosis responses by activating the nitric oxide (NO)-cGMP signaling pathway, and (2) coupling of ₁-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 ₁-adrenoceptor agonist phenylephrine, cGMP accumulation was observed only if slices had been derived from females treated with both E₂ and P before experimentation. Moreover, ₁-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 ₁-adrenoceptor antagonist prazosin on lordosis behavior in E₂- and P-treated female rats. Thus, the NO-cGMP pathway mediates the facilitatory effects of ₁-adrenoceptors on lordosis behavior in female rats, and previous exposure of the HYP and POA to both E₂ and P are required to link ₁-adrenoceptors to this pathway.

Key words: estradiol; progesterone; ₁-adrenoceptors; hypothalamus; lordosis; cGMP

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19167191-07$05.00/0

This article has been cited by other articles:

				O. Gonzalez-Flores, J. Shu, I. Camacho-Arroyo, and A. M. Etgen Regulation of Lordosis by Cyclic 3',5'-Guanosine Monophosphate, Progesterone, and Its 5{alpha}-Reduced Metabolites Involves Mitogen-Activated Protein Kinase Endocrinology, December 1, 2004; 145(12): 5560 - 5567. [Abstract] [Full Text] [PDF]

				A. Quesada and A. M. Etgen Functional Interactions between Estrogen and Insulin-Like Growth Factor-I in the Regulation of alpha 1B-Adrenoceptors and Female Reproductive Function J. Neurosci., March 15, 2002; 22(6): 2401 - 2408. [Abstract] [Full Text] [PDF]

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