Lack of effect of insulin or insulin-like growth factor I on the steroid sulfatase activity of human placental cytotrophoblasts.
Hyperinsulinemia is known to reduce serum dehydroepiandrosterone sulfate (DHEA-S) levels in normal females. A possible mechanism for this phenomenon would be an insulin-mediated increase in steroid sulfatase activity, with insulin acting either via activation of the insulin receptor or via cross-reaction with the insulin-like growth factor I (IGF-I) receptor. Using a well characterized human cytotrophoblast system, the presence of steroid sulfatase activity in isolated cytotrophoblasts was documented. Half maximal cellular hydrolysis of DHEA-S was observed at a substrate concentration of 9.6-14.5 microM, and maximal hydrolysis at a concentration of 75-100 microM. The hypothesis that insulin increases steroid sulfatase activity was examined by exposing cytotrophoblasts to supraphysiological concentrations of either insulin (2 micrograms/ml) or IGF-I (20 ng/ml) for 24 h and then measuring the rate of DHEA-S hydrolysis. Insulin failed to affect cytotrophoblastic steroid sulfatase activity, irrespective of whether the substrate concentration was 20 microM or 100 microM. IGF-I also exerted no effect on steroid sulfatase activity. These data indicate that neither insulin nor IGF-I affect the steroid sulfatase activity of human cytotrophoblasts. An effect of insulin or IGF-I on the steroid-sulfatase activity of other tissues has not been excluded. These observations suggest that the decline in serum DHEA-S levels during hyperinsulinemia is not mediated via an insulin-induced increase in steroid sulfatase activity.
Nestler
J E
JE
Division of Endocrinology and Metabolism, Medical College of Virginia, Virginia Commonwealth University, Richmond.
D001192:Arylsulfatases / Q000378:metabolism*; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000378:metabolism; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000494:pharmacology*; D043266:Steryl-Sulfatase; D013429:Sulfatases / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology / Q000201:enzymology*
D007328:Insulin; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D007334:Insulin-Like Growth Factor I; D013429:Sulfatases; D001192:Arylsulfatases; D043266:Steryl-Sulfatase