Molenda-Figueira Heather A, Williams Casey A, Griffin Andreana L, Rutledge Eric M, Blaustein Jeffrey D, Tetel Marc J
Center for Neuroendocrine Studies, Neuroscience and Behavior Program, University of Massachusetts, Amherst, MA 01003, USA.
Horm Behav. 2006 Sep;50(3):383-92. doi: 10.1016/j.yhbeh.2006.04.005.
The ovarian hormones, estradiol (E) and progesterone (P) facilitate the expression of sexual behavior in female rats. E and P mediate many of these behavioral effects by binding to their respective intracellular receptors in specific brain regions. Nuclear receptor coactivators, including Steroid Receptor Coactivator-1 (SRC-1) and CREB Binding Protein (CBP), dramatically enhance ligand-dependent steroid receptor transcriptional activity in vitro. Previously, our lab has shown that SRC-1 and CBP modulate estrogen receptor (ER)-mediated induction of progestin receptor (PR) gene expression in the ventromedial nucleus of the hypothalamus (VMN) and hormone-dependent sexual receptivity in female rats. Female sexual behaviors can be activated by high doses of E alone in ovariectomized rats, and thus are believed to be ER-dependent. However, the full repertoire of female sexual behavior, in particular, proceptive behaviors such as hopping, darting and ear wiggling, are considered to be PR-dependent. In the present experiments, the function of SRC-1 and CBP in distinct ER- (Exp. 1) and PR- (Exp. 2) dependent aspects of female sexual behavior was investigated. In Exp. 1, infusion of antisense oligodeoxynucleotides to SRC-1 and CBP mRNA into the VMN decreased lordosis intensity in rats treated with E alone, suggesting that these coactivators modulate ER-mediated female sexual behavior. In Exp. 2, antisense to SRC-1 and CBP mRNA around the time of P administration reduced PR-dependent ear wiggling and hopping and darting. Taken together, these data suggest that SRC-1 and CBP modulate ER and PR action in brain and influence distinct aspects of hormone-dependent sexual behaviors. These findings support our previous studies and provide further evidence that SRC-1 and CBP function together to regulate ovarian hormone action in behaviorally-relevant brain regions.
卵巢激素雌二醇（E）和孕酮（P）促进雌性大鼠性行为的表现。E和P通过与特定脑区中各自的细胞内受体结合来介导许多此类行为效应。核受体共激活因子，包括类固醇受体共激活因子-1（SRC-1）和CREB结合蛋白（CBP），在体外显著增强配体依赖性类固醇受体的转录活性。此前，我们实验室已表明，SRC-1和CBP调节雌激素受体（ER）介导的下丘脑腹内侧核（VMN）中孕激素受体（PR）基因表达的诱导以及雌性大鼠激素依赖性性接受能力。在去卵巢大鼠中，高剂量的E alone可激活雌性性行为，因此被认为是ER依赖性的。然而，雌性性行为的全部表现，特别是诸如跳跃、飞奔和耳朵摆动等求偶行为，被认为是PR依赖性的。在本实验中，研究了SRC-1和CBP在雌性性行为不同的ER依赖性（实验1）和PR依赖性（实验2）方面的功能。在实验1中，向VMN中注入针对SRC-1和CBP mRNA的反义寡脱氧核苷酸可降低仅用E治疗的大鼠的脊柱前凸强度，这表明这些共激活因子调节ER介导的雌性性行为。在实验2中，在给予P前后注入针对SRC-1和CBP mRNA的反义寡核苷酸可减少PR依赖性的耳朵摆动、跳跃和飞奔。综上所述，这些数据表明SRC-1和CBP调节大脑中的ER和PR作用，并影响激素依赖性性行为的不同方面。这些发现支持了我们之前的研究，并进一步证明SRC-1和CBP共同发挥作用，以调节行为相关脑区中的卵巢激素作用。
