Distribution of androgen and estrogen receptor mRNA-containing cells in the rat brain: An in situ hybridization study

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Abstract

The distribution of cells that express mRNA encoding the androgen (AR) and estrogen (ER) receptors was examined in adult male and female rats by using in situ hybridization. Specific labeling appeared to be largely, if not entirely, localized to neurons. AR and ER mRNA-containing neurons were widely distributed in the rat brain, with the greatest densities of cells in the hypothalamus, and in regions of the telencephalon that provide strong inputs to the hypothalamus. Thus large numbers of heavily labeled cells were found in the medial preoptic and ventromedial nuclei, each of which is thought to play a key role in mediating the hormonal control of copulatory behavior, as well as in the lateral septal nucleus, the medial and cortical nuclei of the amygdala, the amygdalohippocampal area, and the bed nucleus of the stria terminalis. Heavily labeled ER mRNA-containing cells were found in regions known to be involved in the neural control of gonadotropin release, such as the anteroventral periventricular and the arcuate nuclei, but only a moderate density of labeling for AR mRNA was found over these nuclei. In addition, clearly labeled cells were found in regions with widespread connections throughout the brain, including the lateral hypothalamus, intralaminar thalamic nuclei, and deep layers of the cerebral cortex, suggesting that AR and ER may modulate a wide variety of neural functions. Each part of Ammon's horn contained AR mRNA-containing cells, as did both parts of the subiculum, but ER mRNA appeared to be less abundant in the hippocampal formation. Moreover, AR and ER mRNA-containing cells were also found in olfactory regions of the cortex and in both the main and accessory olfactory bulbs. AR and ER may modulate nonolfactory sensory information as well since labeled cells were found in regions involved in the central relay of somatosensory information, including the mesencephalic nucleus of the trigeminal nerve, the ventral thalamic nuclear group, and the dorsal horn of the spinal cord. Furthermore, heavily labeled AR mRNA-containing cells were found in the vestibular nuclei, the cochlear nuclei, the medial geniculate nucleus, and the nucleus of the lateral lemniscus, which suggests that androgens may alter the central relay of vestibular and auditory information as well. However, of all the regions involved in sensory processing, the heaviest labeling for AR and ER mRNA was found in areas that relay visceral sensory information such as the nucleus of the solitary tract, the area postrema, and the subfornical organ. We did not detect ER mRNA in brainstem somatic motoneurons, but clearly labeled AR mRNA-containing cells were found in motor nuclei associated with the fifth, seventh, tenth, and twelfth cranial nerves. Similarly, spinal motoneurons contained AR but not ER mRNA. Nor was ER mRNA detected in Purkinje cells of the cerebellum, the pontine gray, or inferior olive, all of which harbor AR mRNA, although the parvicellular part of the dentate (lateral cerebellar) nucleus had clearly labeled ER mRNA-containing neurons. The density of labeling in other parts of the brainstem tended to be greatest in those regions that have the strongest connections with the hypothalamus like the midbrain periaqueductal gray, the peripeduncular nucleus, and the locus coeruleus.

Although no absolute sexual dimorphisms in the distributions of AR and ER mRNA-containing cells were found, more subtle quantitative differences between levels of AR and ER mRNA in certain regions of the male and female rat brain cannot be ruled out. In at least a few regions, there appeared to be differences in either the number of cells expressing each receptor mRNA. or in the relative density of labeling over certain cell groups. Whether or not both receptors are contained within individual neurons remains to be demon- strated; however. The remarkable overlap between the distributions of AR and ER mRNA containing neurons suggests that such coexpression is indeed possibility and that the two receptor systems may interact to differentially activate overlapping sets of genes in a variety of neural systems.

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