Yasin M, Dalkin A C, Haisenleder D J, Marshall J C
Department of Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
Endocrinology. 1996 Apr;137(4):1265-71. doi: 10.1210/endo.137.4.8625898.
Pulsatile GnRH stimulates the synthesis and secretion of LH and FSH in both male and female rats. In the male rat, exogenous GnRH pulses increase alpha, LH and FSH beta messenger RNAs (mRNAs) 3-fold within 24 h. In contrast, the results of recent in vivo and in vitro studies have shown that GnRH stimulates an increase in alpha and FSH beta mRNAs, but not LHbeta. However, during the estrous cycle, LHbeta mRNA increases during the GnRH-induced LH surge on proestrus afternoon. This increase in LHbeta mRNA appears to be coincident with a transient rise in serum testosterone (T). Therefore, the present study was conducted to determine whether T has a role in facilitating GnRH stimulation of LHbeta mRNA expression. In the first group of studies, adult female rats were ovariectomized, and T implants were inserted sc 7 days before the study (serum T, 1.86 ng/ml). Animals received iv pulses of GnRH (25 ng; 30-min interval) for 6-24 h (saline pulses to controls). The data showed that in the presence of T, GnRH stimulated a significant increase in LHbeta (as well as alpha and FSH beta) mRNAs within 6 h (P < 0.05 vs. saline-pulsed controls). Other results revealed that T treatment was critical to the stimulatory effect of GnRH on LH beta mRNA. A second group of studies examined the time course and dose effects of T on LH beta mRNA expression. Maximal LH beta mRNA responses to GnRH (3-fold increase vs. saline controls; P < 0.05) were seen after pretreatment with the lowest dose of T examined (serum T, 0.42 ng/ml), which is similar to T concentrations on proestrus. Higher doses of T suppressed LH release, as well as LH mRNA responses to GnRH. The T-induced LHbeta mRNA response to pulsatile GnRH was seen within 24 h of exposure to T and was the result of an androgenic action, as similar results were observed in rats that received dihydrotestosterone. These findings suggest that T is required to facilitate GnRH stimulation of LHbeta mRNA in the female rat. Moreover, in the presence of the concentrations of T seen on proestrus, LHbeta mRNA increases within 6 h, which is similar to the time course seen during the LH surge. Thus, the present results also suggest that the combined effects of the rise in serum T and increased GnRH secretion induce the rapid rise in LHbeta mRNA expression on the afternoon of proestrus.
脉冲式促性腺激素释放激素（GnRH）可刺激雄性和雌性大鼠促黄体生成素（LH）和促卵泡生成素（FSH）的合成与分泌。在雄性大鼠中，外源性GnRH脉冲可在24小时内使α、LH和FSHβ信使核糖核酸（mRNA）增加3倍。相比之下，近期体内和体外研究结果表明，GnRH可刺激α和FSHβ mRNA增加，但不会刺激LHβ mRNA增加。然而，在发情周期中，LHβ mRNA在发情前期下午GnRH诱导的LH峰期间会增加。LHβ mRNA的这种增加似乎与血清睾酮（T）的短暂升高同时出现。因此，本研究旨在确定T是否在促进GnRH对LHβ mRNA表达的刺激作用中发挥作用。在第一组研究中，成年雌性大鼠接受卵巢切除术，并在研究前7天皮下植入T（血清T，1.86 ng/ml）。动物接受静脉注射GnRH脉冲（25 ng；间隔30分钟），持续6 - 24小时（给对照组注射生理盐水脉冲）。数据显示，在有T存在的情况下，GnRH在6小时内刺激LHβ（以及α和FSHβ）mRNA显著增加（与注射生理盐水脉冲的对照组相比，P < 0.05）。其他结果表明，T处理对于GnRH对LHβ mRNA的刺激作用至关重要。第二组研究考察了T对LHβ mRNA表达的时间进程和剂量效应。在用所检测的最低剂量T（血清T，0.42 ng/ml）预处理后，观察到对GnRH的最大LHβ mRNA反应（与生理盐水对照组相比增加3倍；P < 0.05），这与发情前期的T浓度相似。更高剂量的T会抑制LH释放以及LH mRNA对GnRH的反应。在接触T的24小时内可观察到T诱导的LHβ mRNA对脉冲式GnRH的反应，这是雄激素作用的结果，因为在接受双氢睾酮的大鼠中也观察到了类似结果。这些发现表明，在雌性大鼠中，T是促进GnRH刺激LHβ mRNA所必需的。此外，在发情前期所见的T浓度存在时，LHβ mRNA在6小时内增加，这与LH峰期间所见的时间进程相似。因此，本研究结果还表明，血清T升高和GnRH分泌增加的联合作用诱导了发情前期下午LHβ mRNA表达的快速升高。
