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

Abstract

The posterior bed nuclei of the stria terminalis (BST) are important neural substrate for relaying limbic influences to the paraventricular nucleus (PVN) of the hypothalamus to inhibit hypothalamic-pituitary-adrenal (HPA) axis responses to emotional stress. Androgen receptor-expressing cells within the posterior BST have been identified as projecting to the PVN region. To test a role for androgen receptors in the posterior BST to inhibit PVN motor neurons, we compared the effects of the non-aromatizable androgen dihydrotestosterone (DHT), the androgen receptor antagonist hydroxyflutamide (HF), or a combination of both drugs implanted unilaterally within the posterior BST. Rats bearing unilateral implants were analyzed for PVN Fos induction in response to acute-restraint stress and relative levels of corticotrophin-releasing hormone and arginine vasopressin (AVP) mRNA. Glutamic acid decarboxylase (GAD) 65 and GAD 67 mRNA were analyzed in the posterior BST to test a local involvement of GABA. There were no changes in GAD expression to support a GABA-related mechanism in the BST. For PVN neuropeptide expression and Fos responses, basic effects were lateralized to the sides of the PVN ipsilateral to the implants. However, opposite to our expectations of an inhibitory influence of androgen receptors in the posterior BST, PVN AVP mRNA and stress-induced Fos were augmented in response to DHT and attenuated in response to HF. These results suggest that a subset of androgen receptor-expressing cells within the posterior BST region may be responsible for increasing the biosynthetic capacity and stress-induced drive of PVN motor neurons.

Corticotropin-Releasing Factor Modulation of Forebrain GABAergic Transmission has a Pivotal Role in the Expression of Anabolic Steroid-Induced Anxiety in the Female Mouse

“…Our previous studies argue against this mechanism as, although AAS treatment enhanced CRF expression in the extended amygdala, exposure to these steroids did not alter CRF expression in the median eminence or the PVN and did not increase basal levels of serum corticosterone in animals not subjected to behavioral testing (Costine et al, 2010). Interestingly, central treatment of adult male rats with the androgen, dihydrotestosterone, also failed to augment CRF expression in the PVN (Bingham et al, 2011). Here, we extended this analysis by assessing corticosterone levels following i.c.v.…”

PACAP in the BNST Produces Anorexia and Weight Loss in Male and Female Rats

“…For example, Choi et al found that the activation of anterior and posterior BNST regions excites and inhibits HPA activity, respectively (Choi et al, 2007;Choi et al, 2008b). On the other hand, Bingham et al (2011) found that posterior BNST androgen receptor activation led to excitation of the PVN of the hypothalamus in male rats subjected to restraint stress. These data suggest that activation of the anterior and posterior BNST can lead to or inhibit a stress response, although the conditions that lead to excitation or inhibition may be complex (see below).…”

Central Nervous System Control of Gastrointestinal Motility and Secretion and Modulation of Gastrointestinal Functions

“…Furthermore, both estrogen and androgen receptors are expressed within the BNST (445); activation of androgen receptors appears to enhance stress-induced PVN activation and may enhance HPA axis activation (55, 209). Further, the level of CRF within the BNST has been shown to fluctuate in concert with the estrous cycle (360) providing a neurophysiological basis for the differential influence of gender and sex hormones in the modulation of BNST, hence, HPA axis, activity.…”