FETAL ALCOHOL EXPOSURE AND FEMALE REPRODUCTIVE FUNCTION

Young adult female rats exposed to alcohol in utero exhibit several
hormonal abnormalities. One of these is a reduced ability to secrete
luteinizing hormone (LH) in response to estrogen (positive feedback), This
deficit in positive feedback is similar to that previously described in the
middle aged female rat immediately prior to the onset of sterility and
suggest that the female rat expose to ethanol in utero may undergo
premature reproductive senescence. This grant application will describe
some mechanisms which may underlie the reduced positive feedback response
of young adult female rats exposed to ethanol in utero. In addition, a
strategy is proposed and examined in hopes of ameliorating the deficits in
LH secretion in this population of fetal alcohol exposed (FAE) females. The reproductive history of the FAE female will be characterized in terms
of 1) onset of puberty, 2) regularity of cyclicity and onset of persistent
vaginal estrous, 3) proestrus gonadotropin secretion and gonadotropin
response to estrogen and progesterone, 4) reproductive and non-reproductive
behaviors. The mechanisms to be examined which might underlie reduced LH secretion in
FAE females are: 1) Alterations in estrogen sensitivity as revealed by changes in estrogen
receptor (ER). ER concentration and synthesis (determined by in vitro
binding assay, solution hybridization and in situ hybridization. 2) Reductions in gonadotropin releasing hormone (GnRH) concentration as
determined by RIA, synthesis as determined by in situ hybridization or GnRH
secretion as determined using an in vitro perfusion system. Based on our existing knowledge, as therapeutic strategy involving the
prepuberal administration of low doses of estrogen will be evaluated to
determine its potential in ameliorating the observed reduced LH secretion
of FAE females. These studies are important in determining the factors underlying the
reduced reproductive potential of FAE females and to determine the efficacy
of a therapeutic strategy which can be used clinically to ameliorate
reproductive deficits in FAE females.