ALTERATIONS IN THE ESTROGEN-SENSITIVITY OF HYPOTHALAMIC PROENKEPHALINMESSENGER-RNA EXPRESSION WITH AGE AND PRENATAL EXPOSURE TO ALCOHOL

Studies suggest that exposure to alcohol in utero causes reproductive and neuroendocrine deficits in adult female rats. The ventromedial nuc leus of the hypothalamus (VMN) is an estrogen-sensitive brain region w hich is regarded as a primary locus for modulating female reproduction . Proenkephalin (PE) mRNA expression in the VMN is dramatically increa sed by estrogen and this elevation is thought to be involved in modula ting female reproductive behavior and neuroendocrine function. To exam ine whether prenatal alcohol exposure has long-term effects on the abi lity of estrogen to influence hypothalamic PE mRNA levels, female rats at 2-3, 6-7 or 15-18 months of age, derived from alcohol- or control- fed darns, were studied. 7 days following ovariectomy, animals receive d either estrogen or sham treatment for 2 days prior to sacrifice. PE mRNA levels in the VMN and striatum were determined by in situ hybridi zation histochemistry. Film autoradiogram density, numbers of PE mRNA- expressing cells and exposed silver grains/cell were analyzed. Estroge n treatment increased hybridization density, the number of PE mRNA-exp ressing cells and PE mRNA (grains) level/cell. in the VMN of normal ad ult female rats. In old rats, estrogen increased the number of PE mRNA -expressing cells without up-regulating PE mRNA grain density/cell. In fetal alcohol-exposed (FAE) female rats, the number of cells that exp ressed PE mRNA did not increase following estrogen treatment at any ag e. Elevation of grain density/cell following estrogen Tvas observed in FAE animals but only at 7-8 months of age. Overall, these data indica te that the estrogen responsiveness of PE mRNA expression in the VMN d eclines with age and, furthermore, prenatal exposure to alcohol blunts estrogen's effects on PE mRNA expression in the adult VMN. These find ing may help to explain the mechanisms underlying the loss of reproduc tive function observed in FAE females.