Cellular and subcellular localization of androgen receptor immunoreactivity relative to C1 adrenergic neurons in the rostral ventrolateral medulla of male and female rats.

In male and female rats, high androgen levels can increase blood pressure. The C1 area of the rostral ventrolateral medulla (RVLM), which is crucial for blood pressure regulation, contains estrogen receptors (ERs) in pre- and postsynaptic neuronal compartments and is modulated by estrogens (Wang et al. [2006] Brain Res 1094:163-178). In this study, the cellular and subcellular localization of androgen receptors (ARs) in the C1 area was examined in sections from male, proestrus (high estrogen) and diestrus (low estrogen) female rat brains that were immunocytochemically labeled for AR and tyrosine hydroxylase (TH). By light and electron microscopy, AR-labeled nuclei were scattered among TH-labeled somata in the RVLM; significantly more AR-labeled nuclei were seen males compared to females. Electron microscopy revealed that extranuclear AR-immunoreactivity (ir) was in similar profile types in male and female rats. AR-ir was almost exclusively in myelinated and unmyelinated axons and in glia. Rarely, AR-ir was in axon terminals that contacted TH-containing dendrites. AR-labeled axon terminals had large diameters and contained numerous dense-core vesicles, resembling peptide-containing hypothalamic or solitary tract inputs. No nuclear or extranuclear AR-ir was found in TH-labeled perikarya and dendrites although a few non-TH- labeled dendrites contained AR-ir. Qualitatively, more axonal profiles appeared to be present in males compared to females. These studies suggest that, unlike ERs, ARs in male and female rats are almost exclusively positioned on afferents and glia, suggesting that androgens modulate RVLM C1 neurons, and thus blood pressure, through presynaptic and glial signaling.