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
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DOI：
10.1523/jneurosci.19-16-07191.1999
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发表时间：
1999-08-15
影响因子：
5.3
通讯作者：
Etgen, AM
中科院分区：
文献类型：
--
作者：
Chu, HP;Etgen, AM
卵巢激素雌二醇(E-2)和孕酮(P)通过调节下丘脑(HYP)和视前区(POA)肾上腺素受体的表达和信号转导来促进大鼠的前凸行为。介导E-2和P易化的主要肾上腺素能受体亚型是ct-肾上腺素受体。在本研究中，我们验证了以下假设：(1)HYP中的α(1)肾上腺素受体通过激活一氧化氮(NO)-cGMP信号通路来增强前凸反应，以及(2)α(1)肾上腺素受体与该信号转导通路的偶联是激素依赖性的。与去卵巢对照组或仅用E-2或P处理的雌性大鼠的HYP和POA切片相比，用E-2和P处理的动物的HYP和POA切片中cGMP的基础水平显著升高。当去卵巢雌性大鼠的HYP和POA切片与去甲肾上腺素或选择性α(1)肾上腺素受体激动剂苯肾上腺素孵育时，只有在实验前同时用E-2和P处理的雌性大鼠的切片才能观察到cGMP的积累。此外，α(1)-肾上腺素能受体对cGMP合成的刺激可被一氧化氮合酶抑制剂阻断，证实这些受体是通过一氧化氮介导的对可溶性鸟苷酸环化酶的刺激而起作用的。行为学研究进一步证明，细胞通透性cGMP类似物8-溴腺苷-cGMP可逆转α(1)-肾上腺素能受体拮抗剂哌唑嗪对雌鼠前凸行为的抑制作用。因此，NO-cGMP途径介导了α(1)肾上腺素受体对雌性大鼠前凸行为的易化作用，而HYP和POA需要预先暴露于E-2和P，才能将α(1)肾上腺素受体与这一途径联系起来。
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 ct, 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 ovauiectomized 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.