Dalkin A C, Haisenleder D J, Yasin M, Gilrain J T, Marshall J C
University of Virginia Health Science Center, Charlottesville 22908, USA.
Endocrinology. 1996 Feb;137(2):548-54. doi: 10.1210/endo.137.2.8593801.
The activins, hormones produced in the gonads and extragonadal tissues (including the pituitary), rapidly increase FSH beta messenger RNA (mRNA) and FSH secretion. In the rat, activin acts via a family of activin receptor (ActR) subunits that includes at least one type I (ActRI or ALK-2) and two homologous type II (IIA and IIB) subunits. We have previously reported that ActRIIA mRNA rises after ovariectomy (OVX). Potentially, the OVX-induced increases in ActR mRNAs could result from altered activin or the activin-binding protein follistatin. It was the purpose of the current studies to determine whether activin and/or follistatin regulated activin receptor subunit mRNAs. Adult female rat pituitaries were dissociated and plated for 48 h, transferred to wells containing follistatin or activin for 2 or 24 h, then RNA extracted for measurement of ActRI, IIA, and IIB and follistatin mRNAs. All three ActR mRNAs were easily detectable in pituitary RNA, with the relative abundance of ActRI > IIA >> IIB (18:9:1). Between 2-24 h, levels of all three ActR mRNAs increased 2- to 3-fold in wells containing medium alone, whereas levels of follistatin mRNA were unchanged. Follistatin significantly reduced FSH secretion and follistatin mRNA, but not the ActR mRNAs. Activin increased ActRI (4-fold, at 2 h), ActRIIB (2-fold, at 24 h), and follistatin (2-fold, at 24 h) mRNAs and FSH release (2-fold, at 24 h), but did not alter ActRIIA mRNA levels. We conclude that 1) pituitary ActR mRNA expression is under inhibitory tone in vivo, as suggested by the effect of pituitary removal and cell dispersion and an earlier report after OVX. 2) Pituitary-derived activin stimulates follistatin (but not ActR) mRNA production, and additional increases in follistatin mRNA can be induced by exogenous activin. 3) Higher concentrations of activin differentially regulate pituitary ActR mRNA expression, suggesting that activin exerts a positive feedback effect on its own receptor.
激活素是在性腺和性腺外组织（包括垂体）中产生的激素，能迅速增加促卵泡激素β信使核糖核酸（mRNA）和促卵泡激素的分泌。在大鼠中，激活素通过一组激活素受体（ActR）亚基发挥作用，该亚基包括至少一种I型（ActRI或ALK - 2）和两种同源的II型（IIA和IIB）亚基。我们之前报道过，卵巢切除术后（OVX）ActRIIA mRNA会升高。卵巢切除术后激活素受体mRNA的增加可能是由激活素或激活素结合蛋白卵泡抑素的改变引起的。本研究的目的是确定激活素和/或卵泡抑素是否调节激活素受体亚基mRNA。将成年雌性大鼠垂体解离并培养48小时，然后转移到含有卵泡抑素或激活素的孔中培养2或24小时，随后提取RNA以测量ActRI、IIA、IIB和卵泡抑素mRNA。在垂体RNA中很容易检测到所有三种激活素受体mRNA，ActRI、IIA、IIB的相对丰度为18:9:1。在2至24小时之间，仅含培养基的孔中所有三种激活素受体mRNA水平增加了2至3倍，而卵泡抑素mRNA水平未变。卵泡抑素显著降低促卵泡激素分泌和卵泡抑素mRNA，但不影响激活素受体mRNA。激活素增加了ActRI（2小时时增加4倍）、ActRIIB（24小时时增加2倍）和卵泡抑素（24小时时增加2倍）mRNA以及促卵泡激素释放（24小时时增加2倍），但未改变ActRIIA mRNA水平。我们得出以下结论：1）如垂体切除和细胞分散的影响以及卵巢切除术后的早期报告所示体内垂体激活素受体mRNA表达处于抑制状态。2）垂体来源的激活素刺激卵泡抑素（而非激活素受体）mRNA产生，外源性激活素可诱导卵泡抑素mRNA进一步增加。3）较高浓度的激活素对垂体激活素受体mRNA表达有不同调节作用，表明激活素对其自身受体发挥正反馈作用。
