Androgen receptor expressing neurons that project to the paraventricular nucleus of the hypothalamus in the male rat

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.

The Medial Preoptic Nucleus Integrates the Central Influences of Testosterone on the Paraventricular Nucleus of the Hypothalamus and Its Extended Circuitries

“…The high containment of androgen receptors within MPN cells identified as projecting to the PVN region directly could form a basis for this functional dependency (Williamson and Viau, 2007). However, the influence of the MPN might also be mediated indirectly through its projections to and/or through various limbic and forebrain structures implicated in the regulation of stressinduced ACTH release.…”

“…In castrated male rats bearing androgen implants in the MPN, the radius of diffusion was spherical in nature and fairly consistent between animals, never exceeding Ͼ400 m from the edge of the wax implant. Along its rostrocaudal axis, the highest number of ARpositive cells in the MPN that project to the PVN are biased toward the caudal part of the nucleus (Williamson and Viau, 2007). Castrated rats bearing proper implants within the intended caudal level of the MPN showed induction of AR staining in the MPN proper and surround, including parts of the medial preoptic area (Fig.…”

“…This may be mediated by a direct influence of androgen-sensitive projections, because the MPN contains the highest number of androgen receptor (AR)-positive cells in the forebrain identified as projecting to the PVN region (Williamson and Viau, 2007). However, on the basis of previous functional studies by Lund et al (2006) and our own retrograde experiments, testosterone is capable of regulating the HPA axis in the vicinity of the PVN region and within several brain nuclei identified as expressing androgen receptors and projecting to the PVN.…”

Androgen Receptors in the Posterior Bed Nucleus of the Stria Terminalis Increase Neuropeptide Expression and the Stress-Induced Activation of the Paraventricular Nucleus of the Hypothalamus

“…However, several additional forebrain and hypothalamic structures that project to the PVN and/or regulate ACTH release also contain a high number of sex steroid hormone receptors (Williamson and Viau, 2007). This suggests that there is likely a complex network dedicated to the central actions of testosterone on HPA axis responses.…”

“…Lesions studies suggest that cells occupying the posterior division of the BST inhibit PVN and HPA responses, likely provided by GABAergic inputs (Choi et al, 2007). The posterior BST contains one of the highest densities of sex steroid hormone receptors in the forebrain (Shughrue et al, 1997;Simerly, 1993), and a significant complement of PVN-projecting cells in this region contain the androgen receptor (Williamson and Viau, 2007). Furthermore, the posterior BST also sends projections back to the amygdalar and lateral septal nuclei, both of which are putative regulators of the HPA axis.…”