Sex differences in estrogenic regulation of preproenkephalin mRNA levels in the medial preoptic area of prepubertal rats.

Opioids have been implicated in sexual differentiation of the brain and in the regulation of reproductive behavior and endocrinology of mammals. Previous studies have indicated that estrogen administration in adults regulates preproenkephalin MRNA levels in several hypothalamic brain nuclei. We have determined preproenkephalin mRNA levels in estrogen-treated juvenile male and female rats to investigate the developmental pattern of estrogenic regulation of enkephalinergic neurons in the medial preoptic area. Rats were treated with estradiol benzoate (20 microgram/kg/day) or oil from day 21 to 23. Sections of the medial preoptic area (mPOA) were studied by in situ hybridization histochemistry at the single cell level and quantified with the assistance of an image analysis system. Our data indicate that males contain higher levels of preproenkephalin mRNA per neuron than females. In addition, our results indicate that estrogen causes an upward shift in the amount of mRNA expressed per cell, females demonstrating a greater response to estrogen than males. An increase in soma cell area following estrogen treatment was observed only in female mPOA enkephalinergic neurons. Taken together, these results indicate a sex difference in total preproenkephalin levels and in estrogenic regulation of preproenkephalin mRNA in the POA of juvenile rats. These results are discussed in relation to the differential role opioids may play in male and female reproductive physiology.