Effects of ethanol on leptin secretion and the leptin-induced luteinizing hormone (LH) release from late juvenile female rats

Background: Chronic ethanol (EtOH) exposure lowers serum insulin-like growt h factor-1 (IGF-1) and luteinizing hormone (LH) levels and also delays fema le puberty, similar to the deficits in the reproductive system that occur d uring leptin deficiency. Leptin administration restores fertility and gonad otropin secretion in the ob/ob mouse and can induce recovery of reproductiv e function in food-restricted animals. This study assessed the effects of E tOH on serum leptin levels, and whether exogenous leptin administration cou ld restore IGF-1 and LH levels in the EtOH-treated animals. Methods: In the first study, 29-day-old female rats were divided into contr ol and EtOH-treated groups, each of which received their respective diet re gimen for 5 consecutive days. The EtOH-treated animals were subdivided and received an intraperitoneal injection of either leptin (100 mu g/0.1 ml) or saline twice daily. Control animals also received intraperitoneal saline i njections twice daily. On day 34, animals were killed, and serum leptin, LH , and IGF-1 were measured by RIA. In a second study we assessed the acute e ffects of a single 3 g/kg dose of EtOH on the ability of leptin to act cent rally to induce LH release. For this, leptin (1 mu g) was administered via a third ventricular (3V) cannula and blood sampling via jugular cannula. In a third experiment, animals were again subjected to a chronic feeding regi men. When 34 days old, they were killed and the anterior pituitaries remove d and incubated in a static incubation system for 60 min to establish basal LH release, then for an additional 60 min in medium containing leptin (10( -7) M). Results: Chronic EtOH exposure lowered serum leptin (p < 0.01), IGF-1 (p < 0.01), and LH (p < 0.05) levels. Leptin administration to EtOH-treated anim als did not restore serum IGF-1 levels. This peptide did, however, effectiv ely restore LH levels to normal, but did not advance the timing of puberty. Acute EtOH administration was found to block leptin-induced LH release fol lowing central administration of the peptide. Conversely, anterior pituitar ies from control and 5-day EtOH-treated animals that were incubated in vitr o released (p < 0.01) equal amounts of LH in response to leptin (10(-7) M). Conclusions: These data demonstrate that EtOH administration not only can s uppress peripheral levels of leptin, but also blocks its central action to facilitate LH secretion. Although replacement of leptin can reverse the EtO H-induced suppression of LH by a direct action at the level of the pituitar y, it cannot elevate serum IGF-1; a peripheral signal that acts centrally t o stimulate LH releasing-hormone (LHRH)/LH release during the juvenile-peri pubertal transition period, and thus accelerates the initiation of female p uberty. These results demonstrate further the complex actions and interacti ons of multiple hormones involved in the pubertal process and the vulnerabi lity of their actions to the toxic effects of EtOH.