title: 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.
authors.affiliation: Department of Cellular and Physiological Sciences, Life Sciences Centre, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Brenda
authors.initials: B
authors.lastname: Bingham
authors.forename: Clara
authors.initials: C
authors.lastname: Myung
authors.forename: Leyla
authors.initials: L
authors.lastname: Innala
authors.forename: Megan
authors.initials: M
authors.lastname: Gray
authors.forename: Adam
authors.initials: A
authors.lastname: Anonuevo
authors.forename: Victor
authors.initials: V
authors.lastname: Viau
mesh_terms: D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000097:blood / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics / Q000378:metabolism; D002369:Castration; D003345:Corticosterone / Q000097:blood / Q000235:genetics; D013196:Dihydrotestosterone / Q000097:blood / Q000494:pharmacology; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D009479:Neuropeptides / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism*; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism*; D013315:Stress, Psychological / Q000473:pathology*
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D009479:Neuropeptides; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D001127:Arginine Vasopressin; C014290:hydroxyflutamide; D005485:Flutamide; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2; D003345:Corticosterone