Anterior pituitary gene expression with reproductive aging in the female rat.
Anterior pituitary gene expression with reproductive aging in the female rat.
复制标题
雌性大鼠垂体前叶基因表达与生殖衰老的关系。
DOI：
10.1095/biolreprod.106.057877
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发表时间：
2007
影响因子：
3.6
通讯作者：
Halvorson,LisaM
中科院分区：
文献类型：
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作者：
Zheng,Weiming;Jimenez-Linan,Mercedes;Rubin,BeverlyS;Halvorson,LisaM
虽然传统上认为女性的生殖衰老是由于卵泡的丧失，但最近的数据表明，整个下丘脑-垂体-卵巢轴随着时间的推移而发生功能变化。本研究的目的是研究已知对促性腺激素功能有重要作用的因子的年龄相关性基因表达变化，包括1)类固醇激素受体，2)孤儿核受体[Nr5a1(类固醇生成因子-1)和Nr5a2(肝脏受体同源1)]，3)垂体源性多肽(激活素、抑制素和卵泡抑素)，以及4)促性腺激素亚单位和5)GnRH受体。我们选择利用中年大鼠模型进行这些研究。幼年(Y；3月龄)和中年(MA；9月龄至12月龄)大鼠去卵巢，注射雌二醇和孕酮以诱导黄体生成素(LH)峰。与年轻动物相比，中年雌性动物促性腺激素亚单位和GnRH受体的mRNA水平降低，而卵巢切除后Y动物的Nr5a1和卵泡抑素mRNA水平显著高于MA动物。此外，类固醇诱导的这些基因的调节在MA动物中丢失。对Nr5a2、Inhba和Inhbb转录本的调控也仅限于幼年动物。相反，在任何时间点，不同年龄组之间的EsrorPgr家族成员的mRNA水平没有显著差异。虽然这个体内模型使卵巢类固醇水平正常化，但它不能控制GnRH刺激随年龄增长的潜在差异。因此，在第二组实验中，我们使用体外灌流系统来比较脉冲GnRH在两个年龄组中的作用。在两个年龄组中，Y动物的Nr5a1mRNA表达高于MA动物，并且GnRH脉冲显著降低两个年龄组的Nr5a1mRNA表达。随着GnRH的处理，Y动物的卵泡抑素mRNA水平显着增加，而雌性雌性动物的水平没有显着变化。综上所述，这些数据表明，在中年大鼠中，垂体基因表达在卵巢切除后和类固醇诱导激增期间发生了基因特异性的钝化。我们认为，与年龄相关的垂体腺生理变化可能与生殖衰老有关。
Although reproductive aging in women is classically attributed to loss of ovarian follicles, recent data have suggested that the entire hypothalamic-pituitary-ovarian axis undergoes functional changes with time. The aim of this study was to characterize age-related changes in pituitary gene expression for factors with known importance for gonadotroph function, including 1) steroid hormone receptors (EsrandPgr), 2) orphan nuclear receptors [Nr5a1(steroidogenic factor-1) andNr5a2(liver receptor homologue-1)], and 3) pituitary-derived polypeptides (activin, inhibin, and follistatin), as well as 4) gonadotropin subunits and 5) GnRH receptors. We chose to utilize a middle-aged rat model for these studies. Young (Y; 3-mo-old) and middle-aged (MA; 9- to 12-mo-old) rats were ovariectomized, primed with estradiol, and injected with progesterone to induce an LH surge. The mRNA levels for the gonadotropin subunits and GnRH receptors were decreased in middle-aged females relative to young animals.Nr5a1and follistatin mRNA levels were significantly greater in Y versus MA animals following ovariectomy. Furthermore, steroid-induced regulation of these genes was lost in the MA animals. Regulation of theNr5a2,Inhba, andInhbbtranscripts was also limited to the young animals. In contrast, there were no significant differences in the mRNA levels ofEsrorPgrfamily members between age groups at any time point. Although this in vivo model normalizes ovarian steroid levels, it does not control for potential differences in GnRH stimulation with aging. Therefore, in a second set of experiments, we used an in vitro perifusion system to compare the effects of pulsatile GnRH in the two age groups.Nr5a1mRNA expression was greater in Y than MA animals and was significantly decreased by GnRH pulses in both age groups. Follistatin mRNA levels increased significantly with GnRH treatment in Y animals but were not significantly changed in the MA females. Taken together, these data demonstrate gene-specific blunting of pituitary gene expression postovariectomy and during the steroid-induced surge in middle-aged rats. We propose that age-related changes in pituitary physiology may contribute to reproductive senescence.