Changes in androgen receptor, estrogen receptor alpha, and sexual behavior with aging and testosterone in male rats.
Changes in androgen receptor, estrogen receptor alpha, and sexual behavior with aging and testosterone in male rats.
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DOI：
10.1016/j.yhbeh.2010.03.001
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发表时间：
2010-07
影响因子：
3.5
通讯作者：
Gore, Andrea C.
中科院分区：
文献类型：
--
作者：
Wu, Di;Gore, Andrea C.
关键词：
男性生殖老化的特征是从中年开始性行为减少。本研究探讨了雄性大鼠下丘脑中睾酮、雄激素受体（AR）和雌激素受体α（ERα）细胞数量之间的关系及其与性行为的关系。对年轻（3个月）和中年（12个月）大鼠进行性行为测试，然后去势并植入载体或睾酮胶囊。再次测试大鼠的性行为。计数室周前腹侧核和视前内侧核内AR和ERα免疫反应阳性细胞数，并测定血清激素水平。与年轻雄性大鼠相比，中年完整大鼠的所有性行为指标均显著受损。在阉割和睾酮植入后，中年男性的性行为在很大程度上与年轻男性相当。在下丘脑中，睾酮给药组雄性动物的AR细胞密度显著高于溶剂给药组雄性动物（5倍），ERα细胞密度显著低于溶剂给药组雄性动物（6倍），无年龄差异。因此，青年和中年大鼠血清睾酮恢复到相当水平导致相似的视前AR和ERα细胞密度，同时大多数行为恢复。这些数据表明，性行为中与年龄相关的差异不能归因于睾酮的绝对水平，此外，中年大脑保留了对下丘脑AR和ERα表达变化的外源性睾酮的反应能力。我们的研究发现，老年男性睾酮替代对下丘脑受体和行为有深远的影响，对治疗男性年龄相关性性腺功能减退症有潜在的医学意义。
Reproductive aging in males is characterized by a diminution in sexual behavior beginning in middle age. We investigated the relationships among testosterone, androgen receptor (AR) and estrogen receptor alpha (ERα) cell numbers in the hypothalamus, and their relationship to sexual performance in male rats. Young (3 months) and middle-aged (12 months) rats were given sexual behavior tests, then castrated and implanted with vehicle or testosterone capsules. Rats were tested again for sexual behavior. Numbers of AR and ERα immunoreactive cells were counted in the anteroventral periventricular nucleus and the medial preoptic nucleus, and serum hormones were measured. Middle-aged intact rats had significant impairments of all sexual behavior measures compared to young males. After castration and testosterone implantation, sexual behaviors in middle-aged males were largely comparable to those in the young males. In the hypothalamus, AR cell density was significantly (5-fold) higher, and ERα cell density significantly (6-fold) lower, in testosterone- than vehicle-treated males, with no age differences. Thus, restoration of serum testosterone to comparable levels in young and middle-aged rats resulted in similar preoptic AR and ERα cell density concomitant with a reinstatement of most behaviors. These data suggest that age-related differences in sexual behavior cannot be due to absolute levels of testosterone, and further, the middle-aged brain retains the capacity to respond to exogenous testosterone with changes in hypothalamic AR and ERα expression. Our finding that testosterone replacement in aging males has profound effects on hypothalamic receptors and behavior has potential medical implications for the treatment of age-related hypogonadism in men.
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DOI：
10.1073/pnas.0610410104
发表时间：
2007-04-03
影响因子：
11.1
作者：
Crews, David;Gore, Andrea C.;Skinner, Michael K.
通讯作者：
Skinner, Michael K.
影响因子：
2.9
作者：
Edinger, Kassandra L.;Frye, Cheryl A.
通讯作者：
Frye, Cheryl A.
影响因子：
3.2
作者：
Boettner, M.;Leonhardt, S.;Jarry, H.
通讯作者：
Jarry, H.
影响因子：
3.5
作者：
Clancy, AN;Zumpe, D;Michael, RP
通讯作者：
Michael, RP
影响因子：
3.9
作者：
FRANKEL, AI
通讯作者：
FRANKEL, AI