Estrogen differentially regulates neuropeptide gene expression in a sexually dimorphic olfactory pathway.

The posterodorsal part of the medial nucleus of the amygdala (MeAp) receives its major sensory input from the accessory olfactory bulb and projects massively to the medial preoptic nucleus and other sexually dimorphic hypothalamic nuclei thought to play key roles in mediating steroid-sensitive reproductive functions. A combined axonal transport/double-immunohistochemical method was used to show that at least one-quarter of the cholecystokinin-immunoreactive cells in the MeAp cocontain substance P and that a substantial proportion of these cells project to the medial preoptic nucleus. In situ hybridization histochemistry was then used to demonstrate that estrogen regulates the expression of preprocholecystokinin in these cells at the mRNA level in male and female rats. In contrast, levels of preprotachykinin mRNA within the MeAp do not appear to be sensitive to acute changes in circulating gonadal steroids in either sex. Although posttranscriptional regulation of mRNA stability may contribute to the observed effects, it appears likely that estrogen stimulates preprocholecystokinin expression within the MeAp by selectively inducing transcription of the corresponding gene, thereby altering the relative amounts of cholecystokinin and substance P coexpressed within individual neurons of the MeAp that project to the hypothalamus.