Emanuele M A, Tentler J, Emanuele N V, Kelley M R
Department of Molecular and Cellular Biochemistry, Loyola University of Chicago, Stritch School of Medicine, Maywood, IL 60153.
Alcohol. 1991 Sep-Oct;8(5):345-8. doi: 10.1016/0741-8329(91)90543-6.
The suppressive effects of ethanol (EtOH) on the male rodent reproductive axis, especially on serum luteinizing hormone (LH) levels, are well known. In this study we examined, in coordinate fashion, the effects of EtOH on LH secretion and on steady-state levels of the mRNA for the two genes that direct LH synthesis, namely alpha- and beta-LH. A single intraperitoneal (IP) injection of EtOH given to castrated male rats produced a statistically significant fall in serum LH levels at 1.5 (p less than 0.05) and 3 hours (p less than 0.01) after injection compared to saline-injected controls. This effect had dissipated by 24 and 72 hours after treatment. Intrapituitary LH content was significantly increased in EtOH-compared to saline-treated animals 1.5 hours after injection (p less than 0.05) at the same time there was a significant decrease in serum LH. Steady-state levels of beta-LH mRNA were significantly diminished in EtOH-treated animals at 1.5 (p less than 0.05) and 3 hours (p less than 0.001) after injection, but returned to control levels thereafter. Since the half-life of beta-LH mRNA is greater than 8 hours, this fall is most likely due to decreased beta-LH mRNA stability and may also involve decreased beta-LH gene transcription. alpha mRNA levels were unchanged at all time points investigated. These findings were verified in four repetitions of this experiment. These data suggest that the EtOH-induced fall in serum LH is due to impaired secretion of LH and to decreased LH synthesis as indicated by diminished steady-state levels of beta-LH subunit mRNA, secondary mainly to altered mRNA stability.
乙醇(EtOH)对雄性啮齿动物生殖轴的抑制作用,尤其是对血清促黄体生成素(LH)水平的抑制作用,是众所周知的。在本研究中,我们以协同方式研究了乙醇对LH分泌以及对指导LH合成的两个基因(即α-LH和β-LH)的mRNA稳态水平的影响。给去势雄性大鼠单次腹腔注射乙醇后,与注射生理盐水的对照组相比,在注射后1.5小时(p<0.05)和3小时(p<0.01)血清LH水平出现统计学显著下降。该作用在治疗后24小时和72小时消失。与生理盐水处理的动物相比,注射后1.5小时,乙醇处理动物的垂体LH含量显著增加(p<0.05),同时血清LH显著下降。注射后1.5小时(p<0.05)和3小时(p<0.001),乙醇处理动物的β-LH mRNA稳态水平显著降低,但此后恢复到对照水平。由于β-LH mRNA的半衰期大于8小时,这种下降很可能是由于β-LH mRNA稳定性降低,也可能涉及β-LH基因转录减少。在所有研究的时间点,α mRNA水平均未改变。该实验重复四次验证了这些发现。这些数据表明,乙醇诱导的血清LH下降是由于LH分泌受损以及LH合成减少,如β-LH亚基mRNA稳态水平降低所示,主要是由于mRNA稳定性改变所致。