ETHANOL-INDUCED ALTERATIONS IN THE POSTTRANSLATIONAL PROCESSING, BUT NOT SECRETION OF LUTEINIZING-HORMONE-RELEASING HORMONE IN-VITRO

The effects of ethanol (EtOH) on the male hypothalamic pituitary repro ductive axis are multiple and varied. Although direct gonadal toxicity has been reported, hypothalamic-pituitary perturbations have also bee n noted. The difficulty of sampling the hypothalamus has made direct i nvestigation of EtOH-induced alterations on luteinizing hormone-releas ing hormone (LHRH) frought with interpretation problems. To circumvent this, we have conducted a series of experiments exploring the effect of 200 mg% EtOH in vitro on GT1-7 cells, a newly developed LHRH secret ing neural cell line. Cell lines were treated with EtOH-containing or EtOH-free media for 2, 6, 24, or 48 hr. EtOH caused no significant cha nge in LHRH secretion at any time point, although there was a trend to increased secretion after 2 hr EtOH exposure when compared with contr ol. Significantly increased total (i.e., cellular plus secreted) pro-L HRH coupled with significantly reduced cellular LHRH after 6 hr only o f EtOH exposure suggested that EtOH caused a transient decrease in pro cessing from bioinactive pro-LHRH to bioactive LHRH. However, even at this time point, LHRH secretion from these EtOH-exposed cells was no d ifferent than from control cells. Steady-state LHRH mRNA levels were n ot changed by EtOH at any time point. These findings are concordant wi th previous in vitro data using hypothalamic tissue that has similarly demonstrated no effect of EtOH on LHRH secretion. Taken together with the in vivo demonstration that EtOH reduces hypothalamic-pituitary po rtal blood levels of LHRH, these data indicate that EtOH exerts its ef fect either at an extrahypothalamic locus and/or on non-LHRH-producing cells within the hypothalamus.