McAbee M D, DonCarlos L L
Program in Neuroscience, Stritch School of Medicine, Loyola University of Chicago, Maywood, Illinois 60153, USA.
Endocrinology. 1999 Apr;140(4):1807-14. doi: 10.1210/endo.140.4.6632.
By postnatal day 10 (PND-10), males express more androgen receptor (AR) messenger RNA (mRNA) than females in the principal portion of the bed nucleus of the stria terminalis (BSTpr) and medial preoptic area (MPO), but not in the ventromedial hypothalamus. The development of these region-specific sex differences in AR mRNA expression may be critical for the organization of male-typical neural circuitry and may represent the onset of sex differences in the sensitivity of the rat brain to the actions of androgens. In this study, we used a 35S-labeled riboprobe and in situ hybridization to address whether postnatal testosterone exposure is important for the up-regulation of AR mRNA content in the developing rat forebrain. In the BSTpr and the MPO of PND-10 rats, males gonadectomized on PND-0 or PND-5 had lower levels of AR mRNA compared with intact or sham-operated control males. Daily replacement of testosterone to animals gonadectomized on PND-0 maintained AR mRNA content in the BSTpr and the MPO at levels equal to those in intact males. In contrast, there was no effect of gonadectomy or testosterone replacement on AR mRNA expression in the ventromedial hypothalamus. Thus, the postnatal hormonal environment may permit the development of region-specific sex differences in AR mRNA. Significant alterations in AR mRNA expression in the BSTpr and MPO in PND-10 male rats were induced by gonadectomy as late as PND-8. Males gonadectomized on PND-8 had levels of AR mRNA significantly lower than those in intact males, but significantly higher than those in intact females. Further, when animals were gonadectomized on PND-0 and given testosterone on PND-8 and PND-9, levels of AR mRNA were also intermediate between those found in intact males and intact females. The exact time course for transcriptional regulation of AR mRNA in the developing rat brain is unknown. However, others have shown significant regulation of AR mRNA within hours of hormone treatment, so that 2 days of hormone withdrawal or replacement are probably sufficient to achieve new steady state levels of message. Moreover, sexually dimorphic neuronal loss has been documented to peak in hypothalamic cell groups during the first postnatal week. Thus, it is likely that changes in the number of AR mRNA-expressing cells as well as the amount of AR mRNA expression per cell are responsible for the development of male-typical AR mRNA content.
到出生后第10天（PND-10），雄性在终纹床核主部（BSTpr）和内侧视前区（MPO）中表达的雄激素受体（AR）信使核糖核酸（mRNA）比雌性多，但在腹内侧下丘脑则不然。AR mRNA表达中这些区域特异性性别差异的发展，对于雄性典型神经回路的构建可能至关重要，并且可能代表大鼠大脑对雄激素作用敏感性的性别差异的起始。在本研究中，我们使用35S标记的核糖探针和原位杂交技术，来探讨出生后睾酮暴露对于发育中大鼠前脑AR mRNA含量上调是否重要。在PND-10大鼠的BSTpr和MPO中，出生当天（PND-0）或出生后第5天（PND-5）接受性腺切除的雄性，与完整或假手术对照雄性相比，AR mRNA水平较低。对出生当天接受性腺切除的动物每天补充睾酮，可使BSTpr和MPO中的AR mRNA含量维持在与完整雄性相当的水平。相反，性腺切除或睾酮替代对腹内侧下丘脑的AR mRNA表达没有影响。因此，出生后的激素环境可能促使AR mRNA出现区域特异性性别差异。在PND-10雄性大鼠中，直到出生后第8天进行性腺切除，才会导致BSTpr和MPO中AR mRNA表达的显著改变。出生后第8天接受性腺切除的雄性，其AR mRNA水平显著低于完整雄性，但显著高于完整雌性。此外，当动物在出生当天接受性腺切除，并在出生后第8天和第9天给予睾酮时，AR mRNA水平也介于完整雄性和完整雌性之间。发育中大鼠大脑中AR mRNA转录调控的确切时间进程尚不清楚。然而，其他人已经表明，在激素处理数小时内AR mRNA就会受到显著调控，因此2天的激素撤除或替代可能足以达到新的信使稳态水平。此外，有文献记载，出生后第一周下丘脑细胞群中性二态性神经元丢失达到峰值。因此，表达AR mRNA的细胞数量变化以及每个细胞中AR mRNA表达量的变化，很可能是导致雄性典型AR mRNA含量发展的原因。
