Papers by Robin Adams-Hays
Molecular and Cellular Endocrinology, Aug 1, 2002
This study tested the hypothesis that nitric oxide (NO) inhibits the rate-limiting catalytic step... more This study tested the hypothesis that nitric oxide (NO) inhibits the rate-limiting catalytic step in steroidogenesis, cytochrome P450 cholesterol side-chain cleaving enzyme (CYP11A1), independent of soluble guanylyl cyclase (GC-S) stimulation. To assess CYP11A1 activity, pregnenolone levels were quantified in murine adrenocortical Y1 cells in the presence of the 3b-hydroxy-D 5steroid dehydrogenase inhibitor, 2a-cyano-17b-hydroxy-4,4?,17a-trimethylandrost-5-ene-3-one. The NO donor, (Z)-1-[2-(2-aminoethyl-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate(deta nonoate), inhibited vasoactive intestinal peptide-, forskolin-and 22a-hydroxycholesterol (22HC)-facilitated pregnenolonogenesis in the absence of GC-S activation and in the presence of a GC-S inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a ]quinoxalin-1-one (ODQ). CYP11A1 was also heterologously expressed in monkey COS7 cells. Deta nonoate inhibited 22HC-facilitated activity of the over-expressed enzyme in the absence of GC-S activation and in the presence of ODQ. The NO-independent, GC-S agonist, 1-benzyl-3-(5?-hydroxymethyl-2?-furyl)indazole did not inhibit steroidogenesis. The IC 50 for effects of free NO on CYP11A1 was potent and in the 0.4 Á/2 mM range. These results support the hypothesis that NO inhibits the rate-limiting enzyme in steroidogenesis independent of GC-S activation.
In presenting this thesis in partial fulfillment for a graduate degree from the University of Nor... more In presenting this thesis in partial fulfillment for a graduate degree from the University of North Dakota, I agree that pe1111ission for extensive copying for scholarly purposes may be granted by the professor who supervised my thesis work or, in his absence, by the chairperson of the department or the dean of the Graduate School. It is understood that any copying or publication or other use of this thesis or part thereof for financial gain shall not be allowed without my written permission. It is also understood that due to recognition shall be given me and to the University of North Dakota in any scholarly use which may be made of any material in my thesis.
Molecular and Cellular Endocrinology, 2002
This study tested the hypothesis that nitric oxide (NO) inhibits the rate-limiting catalytic step... more This study tested the hypothesis that nitric oxide (NO) inhibits the rate-limiting catalytic step in steroidogenesis, cytochrome P450 cholesterol side-chain cleaving enzyme (CYP11A1), independent of soluble guanylyl cyclase (GC-S) stimulation. To assess CYP11A1 activity, pregnenolone levels were quantified in murine adrenocortical Y1 cells in the presence of the 3b-hydroxy-D 5steroid dehydrogenase inhibitor, 2a-cyano-17b-hydroxy-4,4?,17a-trimethylandrost-5-ene-3-one. The NO donor, (Z)-1-[2-(2-aminoethyl-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate(deta nonoate), inhibited vasoactive intestinal peptide-, forskolin-and 22a-hydroxycholesterol (22HC)-facilitated pregnenolonogenesis in the absence of GC-S activation and in the presence of a GC-S inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a ]quinoxalin-1-one (ODQ). CYP11A1 was also heterologously expressed in monkey COS7 cells. Deta nonoate inhibited 22HC-facilitated activity of the over-expressed enzyme in the absence of GC-S activation and in the presence of ODQ. The NO-independent, GC-S agonist, 1-benzyl-3-(5?-hydroxymethyl-2?-furyl)indazole did not inhibit steroidogenesis. The IC 50 for effects of free NO on CYP11A1 was potent and in the 0.4 Á/2 mM range. These results support the hypothesis that NO inhibits the rate-limiting enzyme in steroidogenesis independent of GC-S activation.
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Papers by Robin Adams-Hays