Estrogen Receptor Immunoreactivity in Specific Brain Areas of the Prairie Vole (Microtus ochrogaster) is Altered by Sexual Receptivity and Genetic Sex

Abstract The prairie vole is a small rodent with an unusual reproductive strategy. A sexually naive female vole requires male contact to initiate the maturation of her reproductive functions. Contact with an unfamiliar adult male vole increases blood estrogen levels, reproductive tissue weights, and brain nuclear estrogen receptor binding levels of female voles. What is not known is: 1) What is the precise distribution of estrogen receptor containing neurons in the prairie vole brain? 2) Does male induced sexual receptivity alter the distribution or number of estrogen receptors in specific brain areas of the female vole? 3) Do male and female voles differ in the distribution or number of estrogen receptor containing neurons? We compared sexually receptive‐male‐exposed females, sexually naive females, and sexually naive males, for the presence of estrogen receptor immunoreactive (ER‐IR) neurons in specific cell groups of the brain. The number of ER‐IR neurons per cell group was counted and the relative amount of immunoreactivity per neuron was measured by densitometry. The neuroanatomical distribution of estrogen receptor containing neurons in the vole was similar to the distribution of estrogen receptors in most rodents. The mean number of ER‐IR neurons did not differ between naive and male‐exposed females. The induction of sexual receptivity however significantly decreased the concentration of estrogen receptor immunoreactivity per neuron in the medial preoptic nucleus, the medial preoptic area, the encapsulated bed nucleus of the stria terminalis, and the ventromedial nucleus of the hypothalamus. Compared with naive males, the mean number of ER‐IR neurons was up to four fold greater in naive females in the medial preoptic nucleus, anteroventral periventricular preoptic nucleus, the encapsulated bed nucleus of the stria terminalis, the medial amygdala, and the ventromedial nucleus of the hypothalamus. Additionally the amount of estrogen receptor immunoreactivity per neuron was considerably greater in the medial preoptic nucleus, the medial preoptic area, the encapsulated bed nucleus of the stria terminalis, and the ventromedial nucleus of the hypothalamus of naive females. If the amount of estrogen receptor per cell is a determinant of a tissue's responsiveness to estrogen, reduced estrogen receptor immunoreactivity in males, and in females exposed to males suggests that they may be less responsive to estrogen than naive females. We propose that this reduced estrogen receptor immunoreactivity in males is a result of reduced estrogen receptor protein levels. Currently, we cannot definitively prove our working hypothesis that decreased estrogen receptor immunoreactivity in females exposed to males is due to reduced receptor levels, and not due to ligand altered epitope availability. Our working hypothesis is supported by the brain region‐specific nature of our findings in the females. Experiments using additional antibodies directed against different epitopes of the estrogen receptor and examining ER mRNA will pursue this hypothesis. Brain regions in which estrogen receptor content differs depending upon genetic sex and experiential factors may be particularly important in the regulation of reproduction.