Betaglycan localization in the female rat pituitary: Implications for the regulation of follicle-stimulating hormone by inhibin
Betaglycan localization in the female rat pituitary: Implications for the regulation of follicle-stimulating hormone by inhibin
复制标题
DOI：
10.1210/en.2003-0670
复制
发表时间：
2003-12-01
期刊：
影响因子：
4.8
通讯作者：
Woodruff, TK
中科院分区：
文献类型：
--
作者：
Chapman, SC;Woodruff, TK
激活素刺激的垂体促性腺激素的FSH合成和分泌受卵巢促性腺激素的负调节;然而，促性腺激素拮抗作用的细胞机制尚不清楚。抑制素和激活素共有一个共同的β-亚基，通过该亚基，抑制素可以与激活素竞争结合激活素II型受体并阻止激活素信号转导。尽管Escherichin与激活素受体结合的亲和力远低于激活素本身，但Escherichin即使在低浓度或等摩尔浓度下也能够抑制激活素刺激的FSH合成和分泌。现在已知TGF β III型受体β聚糖作为一种β受体，其结合β受体并增加它们对激活素II型受体的亲和力，从而增强β受体对激活素信号转导的拮抗作用。然而，尽管在体外的几种细胞模型中β聚糖的特征是一种FSH受体，但这种蛋白在体内FSH调节中的作用尚未得到证实。在这项研究中，我们试图更全面地了解β聚糖在控制促性腺激素释放FSH的功能，通过描述β聚糖在垂体中的免疫定位，并评估其相关性，在整个大鼠发情周期的FSH和FSH的波动。一般来说，β聚糖免疫反应性存在于垂体前叶在所有发情周期的时间点，但仅限于膜的促性腺激素细胞之前和之后的初级和次级FSH激增。重要的是，β聚糖定位于促性腺细胞膜时，卵泡刺激素必须迅速降低FSH到基础水平后，第二次FSH激增。这些数据间接支持β聚糖在体内作为辅受体的作用，这是从垂体中释放卵泡刺激素所需的。
Activin-stimulated FSH synthesis and secretion from the pituitary gonadotrope is negatively modulated by ovarian inhibin; however, the cellular mechanism of inhibin antagonism is unknown. Inhibin and activin share a common beta-subunit through which inhibin can compete with activin for binding to the activin type II receptor and prevent activin signal transduction. Although the affinity of inhibin for binding to the activin receptor is far lower than that of activin itself, inhibin is capable of inhibiting activin-stimulated FSH synthesis and secretion even at low or equimolar concentrations. It is now known that the TGFbeta type III receptor, betaglycan, acts as an inhibin coreceptor that binds the inhibins and increases their affinity for the activin type II receptor, thereby enhancing the antagonistic effect of inhibin on activin signal transduction. Yet, despite the characterization of betaglycan is an inhibin coreceptor in several cell models in vitro, the role of this protein in the regulation of FSH in vivo has not been demonstrated. In this study we sought to understand more fully the function of betaglycan in the control of FSH release by the gonadotrope by describing betaglycan immunolocalization in the pituitary and assessing its correlation to fluctuations in FSH and inhibin throughout the rat estrous cycle. In general, betaglycan immunoreactivity was present in the anterior pituitary at all estrous cycle time points, but was confined to the membrane of gonadotropes just before and after the primary and secondary FSH surges. Importantly, betaglycan localized to the gonadotrope membrane when inhibin must rapidly reduce FSH to basal levels after the secondary FSH surge. These data indirectly support a role for betaglycan in vivo as a coreceptor that is required for inhibin-modulated FSH release from the pituitary.