INFERIOR PETROSAL SINUS SAMPLING IN HEALTHY-HUMAN SUBJECTS REVEALS A UNILATERAL CORTICOTROPIN-RELEASING HORMONE-INDUCED ARGININE-VASOPRESSIN RELEASE ASSOCIATED WITH IPSILATERAL ADRENOCORTICOTROPIN SECRETION

Arginine vasopressin (AVP) acts synergistically with corticotropin-rel easing hormone (CRH) to stimulate ACTH release from the anterior pitui tary, In a previous study of bilateral simultaneous inferior petrosal sinus (IFS) sampling in healthy human subjects, we observed lateralize d ACTH secretion, suggesting lateralized secretion of an ACTH-regulati ng hypothalamic factor, To investigate this possibility, we measured A CTH, CRH, AVP, and oxytocin (OT) levels in the IFS and the peripheral circulation in nine normal volunteers, before and after 1 mu g/kg i.v. bolus ovine CRH (oCRH). At baseline, ACTH, AVP, and OT exhibited a si gnificant (P < 0.05) two to threefold intersinus gradient (ISG), indic ating the existence of a dominant petrosal sinus, Endogenous CRH was u ndetectable in all samples, Despite similar exogenous oCRH levels in b oth petrosal sinuses, oCRH caused a significant increase (P < 0.001) i n the ACTH ISG (15.8+/-5.6, mean+/-SEM), suggesting increased responsi veness of one dominant side of the anterior pituitary. This was associ ated with an ipsilateral CRH-induced AVP release and a significant inc rease (P < 0.01) in the AVP ISG (8.6+/-2.3), suggesting lateralized AV P secretion by the hypothalamus. Furthermore, the increased AVP ISG af ter oCRH correlated strongly with the ACTH ISG (r = 0.92, P < 0.01), o CRH administration did not affect OT, These findings suggest that ther e is a dominant petrosal sinus in healthy volunteers that appears to r eflect a dominant side of the adenohypophysis, characterized by increa sed functional activity and/or responsiveness of the pituitary cortico trophs. This may reflect lateralized hypothalamic and/or suprahypothal amic function resulting in CRH-responsive lateralized secretion of AVP from parvocellular andlor magnocellular axons in the median eminence and the posterior pituitary. Although the functional and teleologic si gnificance of these findings remains to be investigated, our data sugg est a novel mechanism for CRH-mediated ACTH release, namely CRH-induce d release of AVP which then enhances CRH action on the corticotrophs. Furthermore, our data represent the first direct evidence for the conc ept of brain lateralization with respect to neuroendocrine secretion.