FREE ESTRADIOL IN SERUM AND BRAIN UPTAKE OF ESTRADIOL DURING FETAL AND NEONATAL SEXUAL-DIFFERENTIATION IN FEMALE RATS
FREE ESTRADIOL IN SERUM AND BRAIN UPTAKE OF ESTRADIOL DURING FETAL AND NEONATAL SEXUAL-DIFFERENTIATION IN FEMALE RATS
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DOI：
10.1095/biolreprod53.5.1198
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发表时间：
1995-11-01
影响因子：
3.6
通讯作者：
VOMSAAL, FS
中科院分区：
文献类型：
--
作者：
MONTANO, MM;WELSHONS, WV;VOMSAAL, FS
循环中的雌二醇被认为对脑或其他雌激素靶组织的性别分化没有贡献。唯一可用于结合雌激素受体的雌二醇被认为是在脑细胞内通过睾酮芳构化为雌二醇产生的，作为脑中雄激素作用的一部分。然而，我们报告说，游离的，具有生物活性的血清雌二醇浓度在胎儿和新生儿性分化早期，游离雌二醇（不与血浆蛋白结合的浓度）为0.54-2.17 pg/ml，这些值与整个动情周期中成年雌性大鼠所观察到的游离雌二醇浓度范围相同（动情间期= 0.53 pg/ml;动情前期= 2.26 pg/ml），雌二醇在动情间期和动情前期明显具有生理作用。当P日龄雌性幼鼠使用硅橡胶胶囊达到总[H-3]雌二醇49 pg/ml（游离0.61 pg/ml）的稳定生理血液浓度时，回收的[H-3]雌二醇特异性结合脑细胞核，约为2.7 fmol/幼鼠脑或12.4 fmol/mg DNA。脑摄取循环雌二醇的发现与目前的假设相反，这些发现表明，胎儿和新生儿循环中的雌二醇可能能够与睾酮及其代谢产物相互作用，以调节脑和其他雌激素靶组织的性分化。
Circulating estradiol is assumed not to contribute to sexual differentiation of the brain or other estrogen target tissues, The only estradiol available for binding to estrogen receptors is thought to be produced within brain cells by the aromatization of testosterone to estradiol as part of the action of androgen in the brain. However, we report that the concentration of free, biologically active serum estradiol (the concentration not bound to plasma proteins) was 0.54-2.17 pg/ml during the fetal and early neonatal period of sexual differentiation, These values were within the same concentration range for free estradiol observed in adult female rats throughout the estrous cycle (diestrus = 0.53 pg/ml; proestrus = 2.26 pg/ml), and estradiol clearly has physiological effects during diestrus as well as proestrus in adult females. When a stable, physiological blood concentration of [H-3]estradiol of 49 pg/ml total (0.61 pg/ml free) was achieved with Silastic capsules in P-day-old female pups, [H-3]estradiol was recovered specifically bound to brain cell nuclei at approximately 2.7 fmol per pup brain or 12.4 fmol/mg DNA. The finding of brain uptake of circulating estradiol is contrary to current hypotheses, These findings suggest that estradiol in the fetal and neonatal circulation may be able to interact with testosterone and its metabolites to regulate sexual differentiation of the brain and other estrogen target tissues.