Steroidogenic characteristics of a new aldosterone-stimulating factor (ASF) isolated from normal human urine.
The steroidogenic properties of a glycoprotein fraction (urinary ASF), isolated from normal human urine, were studied in collagenase-dispersed rabbit adrenal capsular cells in 1) define the requirements for its steroidogenic activity, and 2) assess its site and mode of action. When incubated with adrenal cell suspension at 37 degrees C for 2 hours, urinary ASF induced dose-related increases in both aldosterone and corticosterone production. However, urinary ASF was less potent (ED50 = 10(-9) M) than either angiotensin II (ED50 = 8 x 10(-11) M) or ACTH (ED50 = 4 x 10(-11) M). Increases in cyclic AMP accompanized the steroidogenic response to ACTH but not to either urinary ASF or AII. Deprivation of potassium in incubation media or the addition of ouabain (1 mM) during incubation completely inhibited the steroidogenic response to either urinary ASF, ACTH, or AII. Like ACTH and AII, urinary ASF increased conversion of corticosterone to aldosterone. Specific competitive antagonist of AII (Sar1, Thr8, AII) and ACTH ([I1e9]ACTH1-24) did not prevent the ASF-induced increase in aldosterone production. These results suggest that urinary ASF is readily distinguishable from ACTH. Although it shares similar steroidogenic properties with AII, the inability of AII antagonist to block its effects suggests that it acts at a separate receptor site.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis / Q000378:metabolism / Q000652:urine*; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000096:biosynthesis / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D006023:Glycoproteins; D006801:Humans; D011188:Potassium / Q000494:pharmacology; D011506:Proteins; D011507:Proteinuria; D011817:Rabbits; D013256:Steroids / Q000096:biosynthesis*
D006023:Glycoproteins; D011506:Proteins; D013256:Steroids; C028798:aldosterone stimulating factor, human; D000804:Angiotensin II; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D000251:Adenosine Triphosphatases; D011188:Potassium; D003345:Corticosterone