Estrogen regulates preproenkephalin-A mRNA levels in the rat ventromedial nucleus: temporal and cellular aspects.

Numerous studies suggest that the ventromedial nucleus of the hypothalamus is a primary locus of control for reproductive behavior in the female rat. The display of lordosis behavior is estrogen dependent and its regulation appears to involve the activity of endogenous opioid circuits in the mediobasal hypothalamus and brainstem. Hypothalamic levels of preproenkephalin-A mRNA and the neuropeptide which it encodes, methionine-enkephalin, are dramatically up-regulated by estrogen. To characterize the temporal and cellular aspects of the effect of an acute exposure to estrogen on preproenkephalin-A mRNA levels in the ventromedial nucleus and arcuate nucleus of the hypothalamus, ovariectomized female rats were injected with 50 micrograms estradiol benzoate and used for quantitative in situ hybridization histochemistry of preproenkephalin-A mRNA. In the ventromedial nucleus, estrogen treatment caused a biphasic increase in the number of preproenkephalin-A mRNA cells. Maximal numbers of cells expressing preproenkephalin-A mRNA were observed at 1 and 48 h after estrogen injection. At 4 and 96 h after estrogen injection, the numbers of preproenkephalin-A mRNA cells were similar to that which was seen in the ovariectomized female. The induction of preproenkephalin-A mRNA expression in cells of the arcuate nucleus followed a similar pattern that peaked 48 h after exposure to estrogen. Levels of preproenkephalin-A mRNA per cell did not change in either nucleus as a function of estrogen treatment. Thus, acute estrogen treatment induces expression of preproenkephalin-A mRNA in populations of cells in the ventromedial hypothalamus and arcuate nucleus in which preproenkephalin-A mRNA expression is undetectable by in situ hybridization in the absence of circulating estrogen.