Kalenga M K, De Gasparo M, Thomas K, De Hertogh R
Department of Obstetrics and Gynecology, University of Louvain, Brussels, Belgium.
J Clin Endocrinol Metab. 1995 Apr;80(4):1233-7. doi: 10.1210/jcem.80.4.7714093.
A complete renin-angiotensin system has been shown to be present in human placenta, but its physiological role is poorly known. To investigate the implication of this system in the regulation of steroid hormone secretion, we studied the effect of angiotensin-II on the release of estradiol and progesterone from human placental explants. Our experiments showed that angiotensin-II stimulated estradiol secretion from term placental explants in a dose- and time-dependent fashion, although progesterone release was unaffected. Estradiol release induced by angiotensin-II (0.2 mumol/L) was blocked by angiotensin AT1 receptor antagonist losartan in a dose-dependent manner, suggesting the involvement of the AT1 receptor subtype in the process. On the contrary, the angiotensin AT2 receptor antagonist PD123319 (1 mumol/L) or the angiotensin AT2 receptor agonist CGP42112A (1 mumol/L) had no effect. Analysis of the amount of steroid hormones in the placental tissues incubated for 12 h showed that angiotensin-II increased estradiol production by 34% compared with the unstimulated explants, whereas the total levels of the estrogen precursor androstenedione and testosterone were decreased by 30-45% in the presence of the peptide, suggesting a stimulatory effect on the aromatization step. This hypothesis was reinforced by the absence of effect of angiotensin-II on both estradiol and testosterone concentrations in the placental explants pretreated with the aromatase inhibitor 4-hydroxyandrostenedione (25 mumol/L). Progesterone synthesis was not affected by angiotensin-II. The present study indicates that angiotensin-II induces the secretion of estradiol from human placenta through the angiotensin AT1 receptor subtype activation, and this effect seems to be linked to the stimulation of local androgen aromatization.
完整的肾素 - 血管紧张素系统已被证明存在于人类胎盘中，但其生理作用却鲜为人知。为了研究该系统在类固醇激素分泌调节中的作用，我们研究了血管紧张素 - II对人胎盘外植体中雌二醇和孕酮释放的影响。我们的实验表明，血管紧张素 - II以剂量和时间依赖性方式刺激足月胎盘外植体分泌雌二醇，尽管孕酮释放未受影响。血管紧张素 - II（0.2 μmol/L）诱导的雌二醇释放被血管紧张素AT1受体拮抗剂氯沙坦以剂量依赖性方式阻断，这表明AT1受体亚型参与了该过程。相反，血管紧张素AT2受体拮抗剂PD123319（1 μmol/L）或血管紧张素AT2受体激动剂CGP42112A（1 μmol/L）没有作用。对培养12小时的胎盘组织中类固醇激素含量的分析表明，与未刺激的外植体相比，血管紧张素 - II使雌二醇产量增加了34%，而在该肽存在的情况下，雌激素前体雄烯二酮和睾酮的总水平降低了30 - 45%，这表明对芳香化步骤有刺激作用。芳香化酶抑制剂4 - 羟基雄烯二酮（25 μmol/L）预处理的胎盘外植体中，血管紧张素 - II对雌二醇和睾酮浓度均无影响，这进一步支持了这一假设。孕酮合成不受血管紧张素 - II影响。本研究表明，血管紧张素 - II通过激活血管紧张素AT1受体亚型诱导人胎盘分泌雌二醇，这种作用似乎与局部雄激素芳香化的刺激有关。
