The anteroventral periventricular nucleus of the hypothalamus (AVPv) is a nodal point in the neural circuitry that controls ovulation in rodents. We previously determined that this important nucleus contains sexually dimorphic populations of opioid neurons, and treatment of newborn female animals with testosterone reverses these sexual dimorphisms. There are 2-3 times as many cells that express the opioid peptide precursor proenkephalin (PENK) in the AVPv of male rats compared with females, but there are five fold more cells that express the prodynorphin (PDYN) mRNA in female animals. During the rodent estrous cycle levels of PDYN mRNA decrease, then increase, during the transition from proestrus to estrus. Although this finding would suggest that progesterone may influence PDYN gene expression in the AVPv, treatment of estrogen primed animals with progesterone had no effect on levels of PDYN. Despite high levels of progesterone receptors in the AVPv, progesterone does not appear to influence PENK gene expression. These peptides do not appear to be co-expressed within individual neurons, so our findings suggest that sex steroids control expression of opioid peptides in the AVPv in a cell type-specific manner. We tested the hypotheses that the differential expression of opioid peptides in the AVPv are due to different patterns of hormone receptor expression by these neurons. Double labeling studies indicate that estrogen receptors are expressed in dynorphin containing neurons in the AVPv and a minority of enkephalinergic neurons also express estrogen receptors. Nearly all of the dynorphin neurons in the AVPv co-express progesterone receptors, but enkephalinergic neurons do not appear to express receptors for progesterone. Thus, opioid peptide containing neurons in the AVPv show distinct patterns of hormonal regulation of gene expression and distinct hormone receptor profiles. In addition, the transcription factors cfos and CREB appear to be hormonally regulated in the AVPV. Work in progress will determine if these transacting factors are differentially expressed in PDYN and PENK neurons of the AVPV. Although it is clear that the AVPv is present in the monkey hypothalamus, the chemical identities of its cells have not been established. Because well characterized species differences exist in the regulation of gonadotropin secretion, species differences in the development and mature regulation of PENK and PDYN expression are also likely. It will be necessary to isolate cDNAs from rhesus macaque brain to synthesize probes for these studies to provide maximum sensitivity.
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