Glucocorticoid regulation of vasopressin V1a receptors in rat forebrain

Vasopressin V1a receptors (V1aRs) are expressed in the septum of the rat brain where they are thought to mediate several of the physiologic and behavioral effects of this neuropeptide. We have investigated the effects of adrenal steroids on forebrain V1aRs, Rats were bilaterally adrenalectomized (ADX) and hormone replaced with either corticosterone (CORT), dexamethasone (DEX) or aldosterone (ALDO) at different concentrations. V1aR mRNA was evaluated using in situ hybridization, and V1aR binding site density was quantified using a specifc iodinated V1aR antagonist [I-125]d(CH2)(5)Sar(7)-AVP (I-125-SAVP). V1aR density in the dorsolateral septum and the bed nucleus of the stria terminalis (BNST) decreased significantly with adrenalectomy, and 5 mu g/100 g b.wt. of DEX was able to restore V1aR binding to levels comparable to those of sham operated controls in both regions. ALDO replacement also elevated V1aR binding in the BNST but not in the septum. In ADX animals given corticosterone in their drinking water, V1aR mRNA levels detected by in situ hybridization increased significantly over the ADX rats given saline. In order to understand the molecular basis of this effect, a putative genomic clone encoding the rat V1aR was isolated, and sequence analysis of the 5' flanking region has revealed the presence of several putative glucocorticoid response elements (GREs). Gel retardation assays were performed using these putative GREs, and two appear to be active in protein binding in glucocorticoid receptor containing nuclear extracts. The glucocorticoid effects on V1aR mRNA and binding, and the presence of putative active GREs in the promoter of the V1aR gene strongly implicate a role for adrenal steroids in the regulation of V1a receptor gene expression in glucocorticoid receptor and/or mineralocorticoid receptor expressing tissues.