No abstract

Activation of the hypothalamic-pituitary-adrenal (HPA) axis is initiated by neurosecretory neurons residing within the medial parvicellular part of the hypothalamic paraventricular nucleus (PVN). Despite the potency by which sex steroids operate on HPA and medial parvocellular responses to stress, previous topographic and phenotypic studies suggest that gonadal steroid hormone receptors are scarcely, if at all, expressed by PVN neurons controlling anterior pituitary corticotropes. Guided by the pattern of retrograde accumulation of fluorogold, we used a direct connectional approach to define the distribution of androgen receptors (AR) and estrogen-beta receptors (ER-beta) within populations of neurosecretory vs. nonneurosecretory neurons in the PVN. Juxtaposition of AR-immunoreactivity (ir) and ER-beta mRNA to the pattern of intravenous fluorogold labeling showed these steroid hormone receptors to be concentrated within portions of the PVN devoid of neurosecretory neurons. Superimposing receptor profiles onto the pattern of spinal retrograde labeling confirmed a selective distribution of AR-ir within autonomic-related cells of the medial parvocellular division, including its dorsal, lateral, and ventral medial components. ER-beta mRNA expression was likewise concentrated within regions accumulating spinal tracer, highest within the ventral aspect of the PVN. These results indicate a direct influence of gonadal hormones on preautonomic effector neurons and remain in keeping with an indirect influence of androgens on adrenocorticotropin-regulating neurons in the PVN.

No abstract

Androgen receptors are distributed throughout the central nervous system and are contained by a variety of nuclei that are known to project to or regulate the paraventricular nucleus (PVN) of the hypothalamus, the final common pathway by which the brain regulates the hypothalamic-pituitary-adrenal (HPA) response to homeostatic threat. Here we characterized androgen receptor staining within cells identified as projecting to the PVN in male rats bearing iontophoretic or crystalline injections of the retrograde tracer FluoroGold aimed at the caudal two-thirds of the nucleus, where corticotropin-releasing hormone-expressing neurons are amassed. Androgen receptor (AR) and FluoroGold (FG) double labeling was revealed throughout the limbic forebrain, including scattered numbers of cells within the anterior and posterior subdivisions of the bed nuclei of the stria terminalis; the medial zone of the hypothalamus, including large numbers of AR-FG-positive cells within the anteroventral periventricular and medial preoptic cell groups. Strong and consistent colabeling was also revealed throughout the hindbrain, predominantly within the periaqueductal gray and the lateral parabrachial nucleus, and within various medullary cell groups identified as catecholaminergic, predominantly C1 and A1 neurons of the ventral medulla. These connectional data predict that androgens can act on a large assortment of multimodal inputs to the PVN, including those involved with the processing of various types of sensory and limbic information, and provide an anatomical framework for understanding how gonadal status could contribute to individual differences in HPA function.

Testosterone contributes to sex differences in hypothalamic-pituitary-adrenal (HPA) function in humans and rodents, but the central organization of this regulation remains unclear. The medial preoptic nucleus (MPN) stands out as an important candidate in this regard because it contains androgen receptors and projects to forebrain nuclei integrating cognitive-affective information and regulating HPA responses to homeostatic threat. These include the HPA effector neurons of the paraventricular nucleus (PVN) of the hypothalamus, medial amygdala, and lateral septum. To test the extent to which androgen receptors in the MPN engage these cell groups, we compared in adult male rats the effects of unilateral microimplants of testosterone and the androgen receptor antagonist hydroxyflutamide into the MPN on acute restraint induced activation and/or neuropeptide expression levels. The basic effects of these implants were lateralized to the sides of the nuclei ipsilateral to the implants. Testosterone, but not hydroxyflutamide implants, decreased stress-induced Fos and arginine vasopressin (AVP) heteronuclear RNA expression in the PVN, as well as Fos expression in the lateral septum. In unstressed animals, AVP mRNA expression in the PVN decreased and increased in response to testosterone and hydroxflutamide MPN implants, respectively. The differential influences of these implants on AVP mRNA expression were opposite in the medial amygdala. These results confirm a role for androgen receptors in the MPN to concurrently modulate neuropeptide expression and activational responses in the PVN and its extended circuitries. This suggests that the MPN is capable of bridging converging limbic influences to the HPA axis with changes in gonadal status.