Sorbonne Paris Cité, Université Paris-Diderot, CNRS, INSERM, Biologie Fonctionnelle et Adaptative UMR 8251, Physiologie de l'Axe Gonadotrope U1133, Paris, France.
APHP CIB GHU Sud Henri Mondor, INSERM IMRB U955, Eq.07, Faculté de Médecine, Créteil, France.
J Endocrinol. 2019 Feb 1;240(2):215-228. doi: 10.1530/JOE-18-0313.
Anti-Müllerian hormone (AMH) regulates ovarian function in cyclic females, notably by preventing premature follicle-stimulating hormone (FSH)-mediated follicular growth and steroidogenesis. Its expression in growing follicles is controlled by FSH and by estradiol (E2). In infantile females, there is a transient increase in the activity of the gonadotrope axis, as reflected by elevated levels of both gonadotropins and E2. We previously demonstrated in mice that elevated FSH concentrations are necessary to induce E2 production by preantral/early antral follicles through the stimulation of aromatase expression without supporting their growth. However, whether this action of FSH could involve AMH is unknown. Here, we show that Amh mRNA and protein abundance and serum AMH levels are elevated in infantile mouse females, compared with those in adults. By experimentally manipulating FSH and E2 levels in infantile mice, we demonstrate that high FSH concentrations lower Amh expression specifically in preantral/early antral follicles, whereas E2 has no effect. Importantly, treatment of infantile ovaries in organotypic cultures with AMH decreases FSH-mediated expression of Cyp19a1 aromatase, but it does not alter the expression of cyclin D2-mediating granulosa cell proliferation. Overall, our data indicate that the infantile elevation in FSH levels suppresses Amh expression in preantral/early antral follicles, thereby favoring Cyp19a1 aromatase expression and E2 production. Together with recent discoveries that AMH can act on both the hypothalamus and the pituitary to increase gonadotropin levels, this work suggests that AMH is a critical regulator of the gonadotrope axis during the infantile period, thereby contributing to adult reproductive function programming.
抗缪勒管激素 (AMH) 在循环雌性动物中调节卵巢功能，特别是通过防止过早的卵泡刺激素 (FSH) 介导的卵泡生长和类固醇生成。其在生长卵泡中的表达受 FSH 和雌二醇 (E2) 的控制。在婴儿期女性中，性腺轴的活性会短暂增加，这反映在两种促性腺激素和 E2 水平的升高。我们之前在小鼠中证明，升高的 FSH 浓度通过刺激芳香化酶表达来诱导原始/早期窦卵泡产生 E2，而无需支持它们的生长，这是必需的。然而，FSH 的这种作用是否涉及 AMH 尚不清楚。在这里，我们显示与成年小鼠相比，幼年小鼠雌性的 Amh mRNA 和蛋白丰度以及血清 AMH 水平升高。通过在婴儿期小鼠中实验性地操纵 FSH 和 E2 水平，我们证明高 FSH 浓度特异性地下调原始/早期窦卵泡中的 Amh 表达，而 E2 没有影响。重要的是，在器官型培养物中用 AMH 处理婴儿期卵巢会降低 FSH 介导的 Cyp19a1 芳香化酶表达，但不会改变调节颗粒细胞增殖的 cyclin D2 表达。总的来说，我们的数据表明，婴儿期 FSH 水平的升高抑制了原始/早期窦卵泡中的 Amh 表达，从而有利于 Cyp19a1 芳香化酶表达和 E2 产生。结合最近发现 AMH 可以作用于下丘脑和垂体以增加促性腺激素水平，这项工作表明 AMH 是婴儿期性腺轴的关键调节因子，从而有助于成年生殖功能的编程。
