Volume 17, Number 7,
Issue of April 1, 1997
pp. 2595-2604
Copyright ©1997 Society for Neuroscience
Effect of Alcohol on the Proestrous Surge of Luteinizing Hormone
(LH) and the Activation of LH-Releasing Hormone (LHRH) Neurons in the
Female Rat
Received Nov. 14, 1996; revised Jan. 13, 1997; accepted Jan. 22, 1997.
Kathleen M. Ogilvie and
Catherine Rivier
Clayton Foundation Laboratories for Peptide Biology, The Salk
Institute for Biological Studies, La Jolla, California 92037
Reproduction is adversely affected by alcohol abuse in humans and
laboratory 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 treatment inhibits the HPG axis by blunting release of
LH-releasing hormone (LHRH) in female rats, by examining the effect of
this drug on the central reproductive endocrine event; i.e., the
proestrous surge of gonadotropins, which triggers ovulation. In a first
series of experiments, we injected alcohol at 8 A.M. and 12 P.M. on
proestrus and measured plasma levels of LH, estradiol (E2),
and progesterone during the afternoons of proestrus and estrus. Alcohol
administration blocked the proestrous surge of LH and ovulation. In
subsequent experiments, alcohol inhibited the surge of LHRH (measured
by push-pull cannulation) and LHRH neuronal activation (measured by
Fos labeling in LHRH neurons). Because alcohol also decreased
E2 levels, we reasoned that it might have prevented
positive feedback; however, alcohol retained its ability to inhibit the
LH surge evoked by E2 implantation in ovariectomized
females, disproving this hypothesis. Additionally, alcohol does not act
via increased corticosteroid secretion, because alcohol also blocked
the proestrous surge in adrenalectomized females. Last, exogenous
administration of LHRH to alcohol-blocked animals evoked LH secretion
and ovulation, indicating that pituitary and/or ovarian function could
be restored by mimicking the hypothalamic signal. Collectively, these
data indicate that in female rats, alcohol inhibits the gonadotropin
surge primarily by decreasing LHRH secretion.
Key words:
luteinizing hormone;
LH;
luteinizing hormone-releasing
hormone;
LHRH;
gonadotropin-releasing hormone;
GnRH;
alcohol;
ethanol;
proestrous