Effects of ovariectomy on the neuroendocrine axes regulating reproduction and energy balance in young cynomolgus macaques.
Effects of ovariectomy on the neuroendocrine axes regulating reproduction and energy balance in young cynomolgus macaques.
复制标题
卵巢切除术对幼年食蟹猴调节生殖和能量平衡的神经内分泌轴的影响。
DOI：
10.1111/j.0953-8194.2004.01143.x
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发表时间：
2004
影响因子：
3.2
通讯作者：
Rance,NE
中科院分区：
文献类型：
--
作者：
Sandoval-Guzmán,T;Stalcup,ST;Krajewski,SJ;Voytko,ML;Rance,NE
中年女性卵巢的退化导致卵巢类固醇的去势水平和垂体前叶促性腺激素分泌增加。妇女的老龄化也伴随着能量稳态的重大变化。我们观察到老年女性下丘脑形态和基因表达的改变，包括神经激肽B（NKB）神经元肥大和基因表达增加，促性腺激素释放激素（GnRH）mRNA水平升高和表达阿黑皮素原（POMC）mRNA的神经元数量减少。为了确定卵巢类固醇的损失是否会在年轻灵长类动物中产生类似的基因表达变化，我们测量了卵巢切除术对年轻食蟹猴中NKB、GnRH和POMC基因表达的影响。我们还测量了血清瘦素和体重，以检查卵巢切除术对能量平衡的影响。与正常对照组相比，去卵巢猴漏斗核中的NKB神经元更大，数量更多，NKB mRNA水平升高。此外，卵巢切除术增加了表达GnRH基因转录本的神经元的数量，并升高了血清促黄体生成素。相比之下，卵巢切除术后，与能量平衡相关的几个参数，包括POMC基因表达、血清瘦素和体重均无变化。因此，在老年妇女中NKB和GnRH基因表达的增加是通过猴子卵巢切除术模拟的，但POMC基因表达和能量平衡的变化不是。这项研究为卵巢功能衰竭导致绝经后妇女NKB和GnRH基因表达增加的假设提供了有力的支持。
Degeneration of the ovary in middle‐aged women results in castrate levels of ovarian steroids and increased gonadotropin secretion from the anterior pituitary gland. Ageing in women is also accompanied by significant changes in energy homeostasis. We have observed alterations in hypothalamic morphology and gene expression in older women, including hypertrophy and increased gene expression of neurokinin B (NKB) neurones, elevated levels of gonadotropin releasing‐hormone (GnRH) mRNA and decreased numbers of neurones expressing pro‐opiomelanocortin (POMC) mRNA. To determine if loss of ovarian steroids could produce comparable changes in gene expression in young primates, we measured the effects of ovariectomy on NKB, GnRH and POMC gene expression in young cynomolgus monkeys. We also measured serum leptin and body weight to examine the consequences of ovariectomy on energy balance. NKB neurones in the infundibular nucleus of ovariectomized monkeys were larger, more numerous and displayed increased levels of NKB mRNA compared to those of intact controls. Moreover, ovariectomy increased the number of neurones expressing GnRH gene transcripts and elevated serum luteinizing hormone. By contrast, several parameters related to energy balance, including POMC gene expression, serum leptin and body weights, were unchanged by ovariectomy. Thus, the rise in NKB and GnRH gene expression in older women was simulated by ovariectomy in monkeys, but the changes in POMC gene expression and energy balance were not. This study provides strong support for the hypothesis that ovarian failure contributes to the increased NKB and GnRH gene expression observed in postmenopausal women.