EFFECTS OF ADRENALECTOMY AND TYPE-I OR TYPE TI GLUCOCORTICOID RECEPTOR ACTIVATION ON AVP AND CRH MESSENGER-RNA IN THE RAT HYPOTHALAMUS

The brain contains two types of adrenal steroid receptors, which play a role in mediating adrenal steroid effects on neuropeptide and other types of gene expression in discrete brain regions. Because the paraventricular nuclei of the hypothalamus (PVN) have adrenal steroid-sensitive neuropeptide systems, they provide a bench-mark to assess the doses of receptor agonists that may act selectively via Type I and Type II receptors. In the present study, in situ hybridization histochemistry was used to examine the effects of adrenalectomy (ADX) and Type I and Type II receptor agonists on arginine vasopressin (AVP) mRNA and corticotropin-releasing hormone (CRH) mRNA in rat brain. In agreement with previous reports, adrenal steroid regulation of AVP and CRH mRNA was found to be mediated primarily through the Type II receptor. Furthermore, adrenalectomy significantly increased AVP mRNA in the parvocelluar region of the hypothalamic paraventricular nucleus (PVN), and systemic administration of the specific Type II agonist, RU28362 (10 mu g/mu l/h), as well as corticosterone (CORT) pellets of 50 and 300 mg, prevented this increase. CRH mRNA was not significantly increased after ADX, but was markedly decreased in the PVN of rats receiving either RU28362 or a 300 mg pellet of CORT. Aldosterone, a specific Type I agonist, did not significantly affect either AVP or CRH mRNA levels when administered at 10 mu g/h. Moreover, in the magnocellular regions of the PVN and SON AVP mRNA did not vary as a function of steroid manipulation. Results for PVN are compared to changes in gene products in hippocampus produced by the same doses of Type I and Type II agonists, in which Type I receptors appear to have a significant role.