Connolly P B, Handa R J, Resko J A
Department of Physiology, Oregon Health Sciences University, Portland 97201.
Endocrinology. 1988 Jun;122(6):2547-53. doi: 10.1210/endo-122-6-2547.
Androgen receptors (AR) were determined in cytosol and nuclear extracts of pituitary and neural tissue from intact male guinea pigs by a binding assay using [3H]dihydrotestosterone as ligand. Saturation analyses of cytosol from hypothalamus-preoptic area (POA)-amygdala regions and anterior pituitary revealed receptors (ARc) with apparent Kd values of 2.52 and 3.83 X 10(-10) M, respectively. Nuclear salt extracts from the same tissues contained receptors (ARn) with Kd values of 4.38 and 5.12 X 10(-10) M. Reproductive behavior of 10 males was observed with receptive females for 10 min once a week. After 4 weeks, half of the animals received 10 mg progesterone (P)/day for an additional 4 weeks. P treatment significantly (P less than 0.05) increased latency to first mount and decreased mounts per test period. After behavioral testing, analysis of the AR content of specific brain regions revealed that the highest concentrations of ARc and ARn were in the POA and medial basal hypothalamus, and the lowest were in the cerebral cortex. The ARn content was significantly suppressed in POA and medial basal hypothalamus (P less than 0.05) from P-treated males compared to the control value. These data show that AR content is highest in areas thought to control behavior and gonadotropin release within the brain of the male guinea pig. In addition, the antiandrogenic actions of P on the central nervous system, which in this experiment were expressed as a significant decline in reproductive behavior, may be explained by its interference with the retention of the AR in the nucleus.
通过使用[3H]双氢睾酮作为配体的结合试验,测定了完整雄性豚鼠垂体和神经组织的胞质溶胶和核提取物中的雄激素受体(AR)。对下丘脑-视前区(POA)-杏仁核区域和垂体前叶的胞质溶胶进行饱和分析,发现受体(ARc)的表观解离常数(Kd)值分别为2.52和3.83×10(-10)M。相同组织的核盐提取物中含有Kd值为4.38和5.12×10(-10)M的受体(ARn)。每周一次观察10只雄性豚鼠与处于接受期的雌性豚鼠进行10分钟的生殖行为。4周后,一半动物额外接受4周每天10mg孕酮(P)的处理。P处理显著(P<0.05)增加了首次骑跨的潜伏期,并减少了每个测试期的骑跨次数。行为测试后,对特定脑区AR含量的分析表明,ARc和ARn的最高浓度位于POA和下丘脑内侧基底部,最低浓度位于大脑皮层。与对照值相比,P处理的雄性豚鼠POA和下丘脑内侧基底部的ARn含量显著降低(P<0.05)。这些数据表明,在雄性豚鼠大脑中,AR含量在被认为控制行为和促性腺激素释放的区域最高。此外,P对中枢神经系统的抗雄激素作用,在本实验中表现为生殖行为显著下降,可能是由于其干扰了AR在细胞核中的保留。