Jahagirdar V, Quadros P S, Wagner C K
Department of Psychology and Centre for Neuroscience Research, University at Albany, SUNY, Albany, NY 12222, USA.
J Neuroendocrinol. 2008 Mar;20(3):359-65. doi: 10.1111/j.1365-2826.2008.01647.x. Epub 2008 Jan 15.
Testosterone secreted by male testes during fetal development is aromatized to oestradiol (E(2)) or reduced to the androgen, dihydrotestosteorne (DHT), within specific tissues. The female brain is assumed to develop in the relative absence of gonadal steroid hormones, as the ovary is steroidogenically quiescent until later in postnatal life. However, the proximity of a female fetus to male littermates in utero can increase her exposure to testosterone, and thereby its metabolites. To date, it is has been difficult to dissociate the effects of male-derived E(2) from those of DHT on the developing female brain. In the present study, anogential distance (AGD) in females was used as an androgen-dependent bioassay, whereas progesterone receptor (PR) expression within the medial preoptic nucleus (MPN) was used as an E-dependent measure. Pregnant dams received the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD), or vehicle from embryonic day 16 (ED16) to ED21. On ED22, AGD and PR-immunoreactivity (-ir) were measured in females that had zero, one, or two males (0-2M) or females that had three, four, or five males (3-5M) in the uterine horn. AGD was significantly greater in 3-5M females compared to 0-2M females, suggesting that male littermates are the source of androgenic exposure in the female fetus. ATD treatment significantly decreased PR-ir in the MPN, demonstrating E(2) regulation of PR. However, the total number of males in the uterine horn did not effect PR expression. There was no correlation between PR-ir and AGD, suggesting that these measures are influenced independently. Together, these results suggest that although male littermates provide a significant source of androgens to female fetuses, the amount of E(2) aromatized from male-derived testosterone may not be the only biologically relevant source of androgens or E(2). Alternative sources of E(2) may be essential in ensuring the normal development of the female brain.
在胎儿发育过程中，雄性睾丸分泌的睾酮会在特定组织内被芳香化为雌二醇（E₂）或还原为雄激素双氢睾酮（DHT）。由于卵巢在出生后才开始具有类固醇生成活性，因此一般认为雌性大脑是在相对缺乏性腺类固醇激素的环境中发育的。然而，雌性胎儿在子宫内与雄性同窝仔的距离较近会增加其接触睾酮及其代谢产物的机会。迄今为止，很难区分雄性来源的E₂和DHT对发育中的雌性大脑的影响。在本研究中，雌性的肛门生殖距离（AGD）被用作雄激素依赖性生物测定指标，而内侧视前核（MPN）内的孕激素受体（PR）表达则被用作E依赖性测量指标。怀孕母鼠从胚胎第16天（ED16）至ED21接受芳香化酶抑制剂1,4,6 - 雄甾三烯 - 3,17 - 二酮（ATD）或溶剂。在ED22时，测量子宫角中有零只、一只或两只雄性（0 - 2M）的雌性或有三只、四只或五只雄性（3 - 5M）的雌性的AGD和PR免疫反应性（-ir）。与0 - 2M雌性相比，3 - 5M雌性的AGD显著更大，这表明雄性同窝仔是雌性胎儿雄激素暴露的来源。ATD处理显著降低了MPN中的PR-ir，证明了E₂对PR的调节作用。然而，子宫角中雄性的总数并未影响PR表达。PR-ir与AGD之间没有相关性，这表明这些测量指标受到独立影响。总之，这些结果表明，虽然雄性同窝仔是雌性胎儿雄激素的重要来源，但从雄性来源的睾酮芳香化而来的E₂量可能不是雄激素或E₂的唯一生物学相关来源。E₂的其他来源可能对确保雌性大脑的正常发育至关重要。
