Effects of vasopressin V1b receptor deficiency on adrenocorticotropin release from anterior pituitary cells in response to oxytocin stimulation

Abstract

Oxytocin (OT) is one of the secretagogues for stress-induced ACTH release. OT-induced ACTH release is reported to be mediated by the vasopressin V1b receptor in the rat pituitary gland, which contains both OT and V1b receptors. We examined OT-induced ACTH release using primary cultures of anterior pituitary cells from wild-type (V1bR+/+) and V1b receptor knockout (V1bR -/-) mice. OT stimulated similar levels of ACTH release from pituitary cells of V1bR+/+ and V1bR-/- mice. OT-induced ACTH release was significantly inhibited by the selective V1b receptor antagonist SSR149415 and the OT receptor antagonist CL-14-26 in V1bR +/+ mice. In addition, cotreatment with SSR149415 at 10-6 M and CL-14-26 at 10-6 M inhibited OT-induced ACTH release to the control level in V1bR+/+ mice. In V1bR-/- mice, OT-induced ACTH release was significantly inhibited by CL-14-26 at 10-8 M and completely inhibited at 10-7 M. These results indicate that OT induces the ACTH response via OT and V1b receptors in V1bR+/+ mice but via only OT receptors in V1bR-/- mice. The gene expression level of the OT receptor was significantly higher in the anterior pituitary gland of V1bR-/- mice than in that of V1bR+/+ mice, suggesting that the OT receptor is up-regulated to compensate for ACTH release under conditions of V1b receptor deficiency. Copyright © 2008 by The Endocrine Society.