Bauer-Dantoin A C, Weiss J, Jameson J L
Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Endocrinology. 1996 May;137(5):1634-9. doi: 10.1210/endo.137.5.8612495.
Follistatin is produced in the gonadotrope and folliculostellate cells of the pituitary gland and is thought to indirectly regulate FSH biosynthesis and secretion through its ability to bind activin. Recent measurements of follistatin gene expression during the rat estrous cycle revealed a marked increase in pituitary follistatin messenger RNA (mRNA) levels at the time of the preovulatory FSH surge. This finding suggests a role for follistatin in the regulation of FSH at this dynamic time of the cycle. The aim of the present study was to identify the hormonal control mechanisms responsible for stimulating follistatin gene expression on proestrus. In particular, the roles of estrogen (E) and GnRH were assessed using an in vivo ovariectomized (OVX) animal model in which steroid priming results in daily gonadotropin surges. Follistatin mRNA and serum FSH levels were unchanged throughout the day in untreated OVX rats. E priming of OVX rats elicited a 2-fold elevation in follistatin mRNA levels between 1600-2000 h coincident with the peak of the E-induced FSH surge. To determine whether this effect of E on follistatin mRNA levels was the result of the direct or indirect effects of E on the pituitary, follistatin mRNA levels were examined in E-primed OVX rats that had been treated with pentobarbital at 1430 h (to block hypothalamic neurosecretion). Pentobarbital treatment prevented the E-induced increase in follistatin mRNA levels, suggesting that the effects of E are mediated via GnRH or other hypothalamic factors. The effects of GnRH on follistatin gene expression were examined further using an in vitro perifusion model. Proestrous or metestrous pituitaries were perifused for 8 h with pulsatile GnRH (one pulse per h), continuous GnRH, or medium only. Continuous GnRH treatment resulted in a significant elevation in follistatin mRNA levels in both proestrous and metestrous pituitaries, whereas pulsatile GnRH had no effect at either cycle stage. These results suggest that the proestrous GnRH surge is responsible at least in part for the elevation in pituitary follistatin mRNA levels that is associated with the primary FSH surge. GnRH-induced follistatin production on proestrus probably plays a role in the dynamic regulation of FSH at this time of the ovulatory cycle.
卵泡抑素由垂体促性腺激素细胞和滤泡星状细胞产生，被认为通过其结合激活素的能力间接调节促卵泡激素（FSH）的生物合成和分泌。最近对大鼠发情周期中卵泡抑素基因表达的测量显示，在排卵前FSH激增时，垂体卵泡抑素信使核糖核酸（mRNA）水平显著升高。这一发现表明卵泡抑素在该周期的这一动态时期对FSH的调节中发挥作用。本研究的目的是确定负责在发情前期刺激卵泡抑素基因表达的激素控制机制。具体而言，使用体内卵巢切除（OVX）动物模型评估雌激素（E）和促性腺激素释放激素（GnRH）的作用，在该模型中，类固醇预处理导致每日促性腺激素激增。在未处理的OVX大鼠中，卵泡抑素mRNA和血清FSH水平在一天中保持不变。对OVX大鼠进行E预处理后，在1600 - 2000 h期间卵泡抑素mRNA水平升高了2倍，这与E诱导的FSH激增峰值一致。为了确定E对卵泡抑素mRNA水平的这种影响是E对垂体的直接还是间接作用的结果，在1430 h用戊巴比妥处理（以阻断下丘脑神经分泌）的E预处理OVX大鼠中检测卵泡抑素mRNA水平。戊巴比妥处理阻止了E诱导的卵泡抑素mRNA水平升高，表明E的作用是通过GnRH或其他下丘脑因子介导的。使用体外灌流模型进一步研究了GnRH对卵泡抑素基因表达的影响。用脉冲式GnRH（每小时一个脉冲）、连续GnRH或仅用培养基对发情前期或动情后期的垂体进行8小时灌流。连续GnRH处理导致发情前期和动情后期垂体中卵泡抑素mRNA水平显著升高，而脉冲式GnRH在两个周期阶段均无作用。这些结果表明，发情前期的GnRH激增至少部分负责与主要FSH激增相关的垂体卵泡抑素mRNA水平的升高。发情前期GnRH诱导的卵泡抑素产生可能在排卵周期的这个时候对FSH的动态调节中发挥作用。
