Ovarian Hormone Dependence of α1-Adrenoceptor Activation of the Nitric Oxide–cGMP Pathway: Relevance for Hormonal Facilitation of Lordosis Behavior
Autor: | Anne M. Etgen, Hsiao-Pai Chu |
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Rok vydání: | 1999 |
Předmět: |
Agonist
medicine.medical_specialty medicine.drug_class Posture Hypothalamus Stimulation Biology Nitric Oxide Article Rats Sprague-Dawley Norepinephrine Sexual Behavior Animal Internal medicine Prazosin medicine Animals Cyclic GMP Progesterone Estradiol General Neuroscience Ovary Lordosis behavior Preoptic Area Rats Preoptic area Endocrinology Ovariectomized rat Female Adrenergic alpha-1 Receptor Agonists Soluble guanylyl cyclase Adrenergic alpha-Agonists Signal Transduction medicine.drug |
Zdroj: | The Journal of Neuroscience. 19:7191-7197 |
ISSN: | 1529-2401 0270-6474 |
DOI: | 10.1523/jneurosci.19-16-07191.1999 |
Popis: | The ovarian hormones estradiol (E(2)) 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 E(2) and P facilitation of lordosis is the alpha(1)-adrenoceptor. In the present studies, we tested the hypotheses that (1) alpha(1)-adrenoceptors in the HYP enhance lordosis responses by activating the nitric oxide (NO)-cGMP signaling pathway, and (2) coupling of alpha(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 E(2) and P when compared with slices from ovariectomized controls or females treated with only E(2) or P. When slices of HYP and POA from ovariectomized female rats were incubated with norepinephrine or the selective alpha(1)-adrenoceptor agonist phenylephrine, cGMP accumulation was observed only if slices had been derived from females treated with both E(2) and P before experimentation. Moreover, alpha(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 alpha(1)-adrenoceptor antagonist prazosin on lordosis behavior in E(2)- and P-treated female rats. Thus, the NO-cGMP pathway mediates the facilitatory effects of alpha(1)-adrenoceptors on lordosis behavior in female rats, and previous exposure of the HYP and POA to both E(2) and P are required to link alpha(1)-adrenoceptors to this pathway. |
Databáze: | OpenAIRE |
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