Abstract
Renal resistance to antidiuretic hormone (ADH) has been speculated to be a mechanism of transient nephrogenic diabetes insipidus occurring during late pregnancy. In order to study possible involvement of ovarian steroids in this mechanism, their effect on cyclic adenosine 3': 5'-monophosphate (cAMP) response to arginine vasopressin (AVP) was examined utilizing rat and human renal medullary cells in monolayer culture. In both rat and human cells, estradiol significantly reduced cAMP response to AVP; estradiol at 1.84×10-8M, 1.84×10-7M and 1.84×10-6M decreased cAMP production stimulated by 10-8M AVP to 78±5%, 67±2%(P<0.05) ana 52±1%(P<0.001) of the control in rat renal cells, respectively, and in human renal cellsthe effect of estradiol was comparable to that in rat cells. In rat renal cells progesterone also reduced cAMP response to AVP dose-dependently; progesterone at 1.59×10-7M, 1.59×10-6M and 1.59×10-5M decreased cAMP production stimulated by 10-8M AVP to 87±1%, 72±5%(P<0.001) and 37±5%(P<0.001) of the control, respectively. On the other hand, corticosterone and dexamethasone at concentrations ranging from 10-8M to 10-5M and aldosterone at concentrations ranging from 10-9M to 10-5M did not alter cAMP response to AVP significantly. The suppressive effect of estradiol increased with time until six hours and thereafter it reached a plateau. Simultaneous addition of estradiol and progesterone resulted in a cumulative suppressive effect. Thus, both estradiol and progesterone reducecd renal cAMP response to AVP. It is suggested that these ovarian steroids themselves may reduce the renal responsiveness to AVP when they increase, for example in late pregnancy.
