Expression of alpha(1b) adrenoceptor mRNA in corticotropin-releasing hormone-containing cells of the rat hypothalamus and its regulation by corticosterone

Considerable evidence supports a role for brainstem adrenergic and noradren ergic inputs to corticotropin-releasing hormone (CRH) cells of the hypothal amic paraventricular nucleus (PVN), in the control of hypothalamic-pituitar y-adrenocortical (HPA) axis function. However, little is known about specif ic adrenoceptor (ADR) subtypes in CRH-containing cells of the PVN. Here we demonstrate, using dual in situ hybridization, that mRNA encoding alpha(1b) ADR is colocalized with CRH in the rat PVN. Furthermore, we confirm that t hese alpha(1b) ADR mRNA-containing cells are stress-responsive, by colocali zation with c-fos mRNA after restraint, swim, or immune stress. To determine whether expression of alpha(1b) ADR mRNA is influenced by circ ulating glucocorticoids, male rats underwent bilateral adrenalectomy (ADX) or sham surgery, and were killed after 1, 3, 7, or 14 d. In situ hybridizat ion revealed levels of alpha(1b) ADR mRNA were increased in the PVN 7 and 1 4 d after ADX, but were not altered in the hippocampus, amygdala, or dorsal raphe. Additional rats underwent ADX or sham surgery and received a cortic osterone pellet (10 or 50 mg) or placebo for 7 d. Corticosterone replacemen t (10 mg) reduced the ADX-induced increase in PVN alpha(1b) ADR mRNA to con trol levels, whereas 50 mg of corticosterone replacement resulted in a decr ease in PVN alpha(1b) ADR mRNA as compared with all other groups. Furthermo re, levels of plasma corticosterone were significantly correlated (inverse relationship) with alpha(1b) ADR mRNA in the PVN. We conclude that alpha(1b) ADR mRNA is expressed in CRH-containing, stress- responsive cells of the PVN and is highly sensitive to circulating levels o f corticosterone. Because activation of the alpha(1B) adrenoceptor is predo minantly excitatory within the brain, we predict that this receptor plays a n important role in facilitation of the HPA axis response.