EFFECT OF ALCOHOL ON THE PROESTROUS SURGE OF LUTEINIZING-HORMONE (LH)AND THE ACTIVATION OF LH-RELEASING HORMONE (LHRH) NEURONS IN THE FEMALE RAT

Reproduction is adversely affected by alcohol abuse in humans and labo ratory animals. In rats, alcohol exposure suppresses both luteinizing hormone (LH) and sex steroid secretion, although consensus is lacking as to which level of the hypothalamic-pituitary-gonadal (HPG) axis is primarily affected. We tested the hypothesis that acute alcohol treatm ent inhibits the HPG axis by blunting release of LH-releasing hormone (LHRH) in female rats, by examining the effect of this drug on the cen tral reproductive endocrine event; i.e., the proestrous surge of gonad otropins, which triggers ovulation. In a first series of experiments, we injected alcohol at 8 A.M. and 12 P.M. on proestrus and measured pl asma levels of LH, estradiol (E(2)), and progesterone during the after noons of proestrus and estrus. Alcohol administration blocked the proe strous surge of LH and ovulation. In subsequent experiments, alcohol i nhibited the surge of LHRH (measured by push-pull cannulation) and LHR H neuronal activation (measured by Fos labeling in LHRH neurons). Beca use alcohol also decreased E(2) levels, we reasoned that it might have prevented positive feedback; however, alcohol retained its ability to inhibit the LH surge evoked by E(2) implantation in ovariectomized fe males, disproving this hypothesis. Additionally, alcohol does not act via increased corticosteroid secretion, because alcohol also blocked t he proestrous surge in adrenalectomized females. Last, exogenous admin istration of LHRH to alcohol-blocked animals evoked LH secretion and o vulation, indicating that pituitary and/or ovarian function could be r estored by mimicking the hypothalamic signal. Collectively, these data indicate that in female rats, alcohol inhibits the gonadotropin surge primarily by decreasing LHRH secretion.