TY - JOUR
T1 - Alterations in the estrogen sensitivity of hypothalamic proenkephalin mRNA expression with age and prenatal exposure to alcohol
AU - Li, Yanbing
AU - McGivern, Robert F.
AU - Nagahara, Alan H.
AU - Handa, Robert J.
N1 - Funding Information:
We acknowledge the technical assistance of George Hejna. This research was presented, in part, at the Research Society on Alcoholism, Maui, HI, June 1994. These studies were supported by USPHS AA08696 (to R.J.H.) and AA06478 (to R.F.M.).
PY - 1997/7
Y1 - 1997/7
N2 - Studies suggest that exposure to alcohol in utero causes reproductive and neuroendocrine deficits in adult female rats. The ventromedial nucleus of the hypothalamus (VMN) is an estrogen-sensitive brain region which is regarded as a primary locus for modulating female reproduction. Proenkephalin (PE) mRNA expression in the VMN is dramatically increased by estrogen and this elevation is thought to be involved in modulating female reproductive behavior and neuroendocrine function. To examine whether prenatal alcohol exposure has long-term effects on the ability 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 dams, were studied. 7 days following ovariectomy, animals received either estrogen or sham treatment for 2 days prior to sacrifice. PE mRNA levels in the VMN and striatum were determined by in situ hybridization histochemistry. Film autoradiogram density, numbers of PE mRNA-expressing cells and exposed silver grains/cell were analyzed. Estrogen treatment increased hybridization density, the number of PE mRNA-expressing cells and PE mRNA (grains) level/cell in the VMN of normal adult 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 expressed PE mRNA did not increase following estrogen treatment at any age. Elevation of grain density/cell following estrogen was observed in FAE animals but only at 7-8 months of age. Overall, these data indicate that the estrogen responsiveness of PE mRNA expression in the VMN declines with age and, furthermore, prenatal exposure to alcohol blunts estrogen's effects on PE mRNA expression in the adult VMN. These finding may help to explain the mechanisms underlying the loss of reproductive function observed in FAE females.
AB - Studies suggest that exposure to alcohol in utero causes reproductive and neuroendocrine deficits in adult female rats. The ventromedial nucleus of the hypothalamus (VMN) is an estrogen-sensitive brain region which is regarded as a primary locus for modulating female reproduction. Proenkephalin (PE) mRNA expression in the VMN is dramatically increased by estrogen and this elevation is thought to be involved in modulating female reproductive behavior and neuroendocrine function. To examine whether prenatal alcohol exposure has long-term effects on the ability 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 dams, were studied. 7 days following ovariectomy, animals received either estrogen or sham treatment for 2 days prior to sacrifice. PE mRNA levels in the VMN and striatum were determined by in situ hybridization histochemistry. Film autoradiogram density, numbers of PE mRNA-expressing cells and exposed silver grains/cell were analyzed. Estrogen treatment increased hybridization density, the number of PE mRNA-expressing cells and PE mRNA (grains) level/cell in the VMN of normal adult 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 expressed PE mRNA did not increase following estrogen treatment at any age. Elevation of grain density/cell following estrogen was observed in FAE animals but only at 7-8 months of age. Overall, these data indicate that the estrogen responsiveness of PE mRNA expression in the VMN declines with age and, furthermore, prenatal exposure to alcohol blunts estrogen's effects on PE mRNA expression in the adult VMN. These finding may help to explain the mechanisms underlying the loss of reproductive function observed in FAE females.
KW - Aging
KW - Estrogen
KW - Fetal alcohol exposure
KW - Proenkephalin
KW - Ventromedial nucleus
KW - mRNA
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U2 - 10.1016/S0169-328X(97)00050-8
DO - 10.1016/S0169-328X(97)00050-8
M3 - Article
C2 - 9221919
AN - SCOPUS:0030945561
SN - 0169-328X
VL - 47
SP - 215
EP - 222
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 1-2
ER -