TY - JOUR
T1 - Studies of the inactivation of human placentae aromatase by 17α-ethynyl-substituted 10β-hydroperoxy and related 19-nor steroids
AU - Covey, Douglas F.
AU - Hood, William F.
AU - McMullan, Patrick C.
N1 - Funding Information:
Acknowledgements-Thisw ork was supported by NIH Grant CA 23582.D . F. C. is the recipient of an NIH ResearchC areer DevelopmentA ward CA 00829.
PY - 1986/5/15
Y1 - 1986/5/15
N2 - The inactivation of human placental aromatase by 17α-ethynyl-10β-hydroperoxy-17β-hydroxy -4-estren-3-one (SCH 10015) was investigated. In either the presence or absence of added NADPH, SCH 10015 (Ki = 41 μM) caused a time-dependent loss of aromatase activity (e.g. 50% loss after 20 min with 20 μM SCH 10015). Evidence for the oxidation of an active site sulfhydryl group as the molecular basis for SCH 10015 inactivation is presented. The contraceptive 17α-ethynyl-substituted 19-nor steroids, norethisterone (Ki = 48 μM) and norethynodrel (Ki = 38 μM), were evaluated and found not to inactivate aromatase, suggesting that the potential conversion of either compound to SCH 10015 did not occur to a significant extent in these microsomal incubations. It is speculated that the previously observed potent contraceptive effects of SCH 10015 may have been the result of irreversible inhibition of estrogen biosynthesis.
AB - The inactivation of human placental aromatase by 17α-ethynyl-10β-hydroperoxy-17β-hydroxy -4-estren-3-one (SCH 10015) was investigated. In either the presence or absence of added NADPH, SCH 10015 (Ki = 41 μM) caused a time-dependent loss of aromatase activity (e.g. 50% loss after 20 min with 20 μM SCH 10015). Evidence for the oxidation of an active site sulfhydryl group as the molecular basis for SCH 10015 inactivation is presented. The contraceptive 17α-ethynyl-substituted 19-nor steroids, norethisterone (Ki = 48 μM) and norethynodrel (Ki = 38 μM), were evaluated and found not to inactivate aromatase, suggesting that the potential conversion of either compound to SCH 10015 did not occur to a significant extent in these microsomal incubations. It is speculated that the previously observed potent contraceptive effects of SCH 10015 may have been the result of irreversible inhibition of estrogen biosynthesis.
UR - http://www.scopus.com/inward/record.url?scp=0022459158&partnerID=8YFLogxK
U2 - 10.1016/0006-2952(86)90321-7
DO - 10.1016/0006-2952(86)90321-7
M3 - Article
C2 - 3707596
AN - SCOPUS:0022459158
SN - 0006-2952
VL - 35
SP - 1671
EP - 1674
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 10
ER -