A membrane-associated progesterone-binding protein, 25-Dx, is regulated by progesterone in brain regions involved in female reproductive behaviors
A membrane-associated progesterone-binding protein, 25-Dx, is regulated by progesterone in brain regions involved in female reproductive behaviors
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DOI：
10.1073/pnas.97.23.12816
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发表时间：
2000-11-07
影响因子：
11.1
通讯作者：
Pfaff, DW
中科院分区：
文献类型：
--
作者：
Krebs, CJ;Jarvis, ED;Pfaff, DW
下丘脑腹内侧区 (VMH) 在调节女性生殖行为前凸方面发挥着核心作用，这种行为依赖于卵巢类固醇激素雌二醇 (E) 和黄体酮 (P) 受体的顺序激活。这些受体充当转录因子来改变靶基因的表达。发现 VMH 中 E 和 P 靶向的行为相关基因。我们使用差异显示PCR来鉴定仅用E治疗的卵巢切除（ovx）大鼠与用E和P治疗的卵巢切除大鼠相比，其下丘脑中差异表达的信使RNA。我们在此表明，下丘脑内一种有趣的mRNA在E启动后被P抑制，编码蛋白25-Dx，人膜相关P结合蛋白Hpr6.6的大鼠同源物。大脑中含有最高水平 25-Dx 的神经元位于基底前脑的几个核中，包括 VMH。雌性 P 受体“基因敲除”小鼠下丘脑中 25-Dx 的表达也高于其野生型同窝小鼠。这些发现表明核 P 受体的激活抑制膜 P 受体的表达的机制。 25-Dx，脊柱前凸促进期间。
The ventromedial hypothalamus (VMH) plays a central role in the regulation of the female reproductive behavior lordosis, a behavior dependent upon the sequential activation of receptors for the ovarian steroid hormones estradiol (E) and progesterone (P). These receptors function as transcription factors to alter the expression of target genes. To discover behaviorally relevant genes targeted by E and P in the VMH. we used the differential display PCR to identify messenger RNAs that are differentially expressed in the hypothalamus of ovariectomized (ovx) rats treated with E alone compared with ovariectomized rats treated with E and P. We show here that one interesting mRNA within the hypothalamus that is repressed by P after E priming encodes the protein 25-Dx, the rat homolog of the human membrane-associated P-binding protein Hpr6.6. Neurons in the brain containing the highest levels of 25-Dx are located in several nuclei of the basal forebrain, including the VMH. 25-Dx expression is also higher in the hypothalamus of female P receptor "knockout" mice than in their wild-type littermates. These findings suggest a mechanism in which the activation of nuclear P receptor represses expression of a membrane P receptor. 25-Dx, during lordosis facilitation.