Inhibin binding protein in rats: alternative transcripts and regulation in the pituitary across the estrous cycle.
Inhibin binding protein in rats: alternative transcripts and regulation in the pituitary across the estrous cycle.
复制标题
DOI：
10.1210/mend.15.4.0630
复制
发表时间：
2001-04
影响因子：
--
通讯作者：
Daniel J. Bernard;Teresa K Woodruff
中科院分区：
文献类型：
--
作者：
Daniel J. Bernard;Teresa K Woodruff
抑制素结合蛋白(InhBP)和转化生长因子-β(TGF-β)III型受体β-葡聚糖已被确定为可能的抑制素辅受体。在这里，我们在大鼠中克隆了InhBP基因，并预测它编码一个大的跨膜蛋白，该蛋白是免疫球蛋白超家族的一部分，就像人类所描述的那样。在成年大鼠脑垂体中检测到两个丰富的InhBP转录本(4.4和1.8kb)。较大的转录本编码全长蛋白质，而1.8kb的转录本(InhBP-Short或InhBP-S)对应于受体的剪接变体。这个截短的异构体只包含N-末端信号肽和在全长InhBP(InhBP-Long或InhBP-L)中观察到的前两个(12个)Ig样结构域。InhBP-S不含跨膜区，预测为可溶性蛋白。在脑下垂体中也检测到了β-葡聚糖，但在中间叶中含量最高。虽然我们也观察到垂体前叶中的β-葡聚糖免疫阳性细胞，但它们很少与FSH-β产生细胞共存。接下来，我们研究了大鼠发情周期中辅助受体的生理调节。与循环抑制素A和B一样，垂体InhBP-L和InhBP-S的mRNA水平在整个周期内受到动态调节，并与血清FSH水平呈负相关。两种形式的InhBP的表达也与血清抑制素B水平呈正相关，但与抑制素A水平无关。这些数据特别有趣，因为我们在体外观察到InhBP可能作为抑制素B特异性的辅助受体发挥作用。垂体β-葡聚糖的mRNA水平在整个周期中没有波动，也没有与血清FSH相关。这些观察，再加上它在脑下垂体中的表达模式，表明β-糖蛋白的功能可能不仅仅是脑下垂体内的抑制素辅助受体。InhBP或β-葡聚糖在体内抑制素调节垂体FSH中的直接作用尚未确定，但证明整个发情周期中垂体InhBP的动态调节及其与血清FSH的负相关是朝着这一方向迈出的重要一步。
Inhibin binding protein (InhBP) and the transforming growth factor-beta (TGF beta) type III receptor, beta glycan, have been identified as putative inhibin coreceptors. Here we cloned the InhBP cDNA in rats and predict that it encodes a large membrane-spanning protein that is part of the Ig superfamily, as has been described for humans. Two abundant InhBP transcripts (4.4 and 1.8 kb) were detected in the adult rat pituitary. The larger transcript encodes the full-length protein while the 1.8-kb transcript (InhBP-short or InhBP-S) corresponds to a splice variant of the receptor. This truncated isoform contains only the N-terminal signal peptide and first two (of 12) Ig-like domains observed in the full-length InhBP (InhBP-long or InhBP-L). InhBP-S does not contain a transmembrane domain and is predicted to be a soluble protein. Beta glycan was also detected in the pituitary; however, it was most abundant within the intermediate lobe. Although we also observed beta glycan immunopositive cells in the anterior pituitary, they rarely colocalized with FSH beta-producing cells. We next examined physiological regulation of the coreceptors across the rat estrous cycle. Like circulating inhibin A and inhibin B levels, pituitary InhBP-L and InhBP-S mRNA levels were dynamically regulated across the cycle and were negatively correlated with serum FSH levels. Expression of both forms of InhBP was also positively correlated with serum inhibin B, but not inhibin A, levels. These data are particularly interesting in light of our in vitro observations that InhBP may function as an inhibin B-specific coreceptor. Pituitary beta glycan mRNA levels did not fluctuate across the cycle nor did they correlate with serum FSH. These observations, coupled with its pattern of expression within the pituitary, indicate that beta glycan likely functions as more than merely an inhibin coreceptor within the pituitary. A direct role for InhBP or beta glycan in regulation of pituitary FSH by inhibin in vivo has yet to be determined, but the demonstration of dynamic regulation of pituitary InhBP and its negative relation to serum FSH across the estrous cycle is an important step in this direction.