Sustained effects of a single injection of ethanol on the hypothalamic-pituitary-gonadal axis in the male rat

Abstract

The hormones responsible for regulating the hypothalamic-pituitary-gonadal axis are essential for proper reproductive function. Ethanol (EtOH) has been shown to exert its effect at all three levels of this axis. The present study defines striking differences in the time course of recovery of luteinizing hormone (LH) in gonadally intact, compared with, castrated male rats after acute EtOH administration. Serum levels of LH and testosterone were measured at various time points up to 2 weeks (1.5, 3, 24, 48, 72, 96, 168, and 336 hr) after a single intraperitoneal injection of either saline or 3 g/kg of EtOH in intact adult male rats. One EtOH injection significantly suppressed testosterone levels as low as 20% (p < 0.01) of saline-injected intact rats. This occurred as early as 1.5 hr after EtOH administration (the first measured time point), and statistically significant suppression was sustained for 96 hr. Similarly, LH levels showed a significant decrease. However, this significant fall in LH did not begin until 3 hr (p < 0.05) and continued up to 96 hr (p < 0.01), with a gradual return to control levels at 168 and 336 hr after treatment. Despite the significant and prolonged fall in testosterone levels in the EtOH-treated intact rats, beta-LH mRNA levels were inappropriately not elevated, as would be expected in the context of low circulating testosterone. However, at 168 and 336 hr, steady-state levels of beta-LH mRNA were significantly higher than seen in saline-injected controls (p < 0.05 and p < 0.01, respectively), temporally correlating with the return of serum LH to control. LH levels in the castrated animals were significantly suppressed at 1.5 hr (p < 0.05) and 3 hr (p < 0.01) after EtOH treatment, compared with controls, yet they returned much more quickly by 24 hr after treatment. beta-LH mRNA levels of castrated animals also showed a significant depression at 1.5 and 3 hr, and returned to control levels by 24 hr. In these rats, the hypothalamic LH-releasing hormone mRNA levels were not altered by a single EtOH injection at any time point. However, in the intact animals, there was a transient increase in LH-releasing hormone mRNA at 72 and 96 hr (p < 0.01 and p < 0.05, respectively) that may lead to the upregulation of beta-LH mRNA expression. These studies indicate that EtOH causes prolonged decreases in important serum hormones that are essential to the reproductive axis of the adult male rat.