Pluchino Nicola, Ninni Filippo, Casarosa Elena, Lenzi Elena, Begliuomini Silvia, Cela Vito, Luisi Stefano, Freschi Letizia, Merlini Sara, Giannini Andrea, Cubeddu Alessandra, Genazzani Andrea Riccardo
Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy.
J Sex Med. 2008 Dec;5(12):2780-92. doi: 10.1111/j.1743-6109.2008.00999.x.
Clinical and biological evidences have shown a wide range of neuroactive effects of testosterone administration.
Evaluation of the effects of 2-weeks treatment with testosterone (T), Dihydrotestosterone (DHT), and estradiol valerate (E2V) on brain and serum allopregnanolone (AP) in gonadectomized rats of both sexes.
AP levels were measured in frontal and parietal lobe, hippocampus, hypothalamus, anterior pituitary, and in serum.
Eight groups of Wistar female and eight groups of Wistar male rats were included. For each sex, one group of fertile and one group of gonadectomized rats were employed as control receiving placebo. The others groups received subcutaneous T at the dose of 10 microg/kg/day and 100 microg/kg/day for female rats, and 1 mg/kg/day and 5 mg/kg/day for male rats, or DHT at the doses of 1 microg/kg/day, 10 microg/kg/day, and 100 microg/kg/day for females, and 0, 1 microg/kg/day, 1 mg/kg/day and 5 mg/kg/day for males, or E2V (0.05 mg/Kg/day).
Ovariectomy (OVX) and orchidectomy (OCX) induced a significant decrease in AP in all brain areas analyzed, as well as in serum. In OVX rats, T replacement, as well as E2V, significantly increased AP content in all brain areas and in plasma. In OCX, T and E2V did not actively result in influencing AP concentration in frontal and parietal lobe, while it produced a significant rise in AP levels in the hippocampus, hypothalamus, anterior pituitary, and serum. Conversely, DHT replacement had no affect on AP levels anywhere or at any administered dose, either in males or in female rats.
Gender difference and T therapy affect brain AP synthesis/release during the reproductive aging. This effect becomes particularly evident in the brain of ovariectomized animals, where the content of this specific neurosteroid is much more responsive than male animals to testosterone replacement.
临床和生物学证据表明，睾酮给药具有广泛的神经活性作用。
评估睾酮（T）、双氢睾酮（DHT）和戊酸雌二醇（E2V）对两性去势大鼠脑和血清中孕烷醇酮（AP）的影响，为期2周。
测量额叶、顶叶、海马体、下丘脑、垂体前叶及血清中的AP水平。
纳入八组雌性Wistar大鼠和八组雄性Wistar大鼠。对于每种性别，一组正常生育大鼠和一组去势大鼠作为接受安慰剂的对照组。其他组雌性大鼠皮下注射剂量为10微克/千克/天和100微克/千克/天的T，雄性大鼠皮下注射剂量为1毫克/千克/天和5毫克/千克/天的T，或雌性大鼠皮下注射剂量为1微克/千克/天、10微克/千克/天和100微克/千克/天的DHT，雄性大鼠皮下注射剂量为0、1微克/千克/天、1毫克/千克/天和5毫克/千克/天的DHT，或皮下注射剂量为0.05毫克/千克/天的E2V。
卵巢切除术（OVX）和睾丸切除术（OCX）导致所有分析脑区以及血清中的AP显著降低。在OVX大鼠中，T替代以及E2V显著增加了所有脑区和血浆中的AP含量。在OCX大鼠中，T和E2V对额叶和顶叶的AP浓度没有积极影响，而在海马体、下丘脑、垂体前叶和血清中AP水平显著升高。相反，无论在雄性还是雌性大鼠中，DHT替代在任何给药剂量下对任何部位的AP水平均无影响。
在生殖衰老过程中，性别差异和T治疗会影响脑AP的合成/释放。这种影响在去势动物脑中尤为明显，在这种特定神经甾体的含量方面，去势动物脑比雄性动物对睾酮替代的反应更敏感。
