TY - JOUR
T1 - Metabolism of 19-methyl substituted steroids and a proposal for the third aromatase monooxygenation
AU - Covey, Douglas F.
AU - Carrell, H. L.
AU - Beusen, Denise D.
N1 - Funding Information:
This work was supported by National Institutes of Health Grants CA-23582, GM-07067, CA-10925, CA-06927, CA-22780, RR-00954, RR-05539, RR-00204, and an appropriation from the Commonwealth of Pennsylvania. D.F.C. is the recipient of Research Career Development Award CA-00829 from the National Institutes of Health. D.D.B. was supported by National Institutes of Health Training Grant 5T32HL07275.
PY - 1987
Y1 - 1987
N2 - The article summarizes the results of recent studies on the metabolism of 10-ethylestr-4-ene-3,17-dione, 10-[(1R)-1-hydroxyethyl]-,and 10-[(1S)-1-hydroxyethyl]estr-4-ene-3, 17-dione, in placenta. These compounds are the 19-methyl analogs of androstenedione, 19-hydroxyandrostenedione, and 19-oxoandrostenedione, respectively. No conversion of 10-ethylestr-4-ene-3,17-dione to either estrogens or oxygenated metabolites was detected. Both 10-[(1R)-1-hydroxyethyl]- and 10-[(1S)-1-hydroxyethyl]estr-4-ene-3, 17-dione were oxygenated to 10-(1,1-dihydroxyethyl)estr-4-ene-3,17-dione and isolated following in situ dehydration as 10-acetylestr-4-ene-3,17-dione. Evidence for the involvement of aromatase in these conversions is discussed. No conversion of 10-acetylestr-4-ene-3,17-dione to either estrogens or other oxygenated products was detected. These results lead us to propose a new mechanism for the third aromatase monooxygenation. We propose that the third oxygenation is initiated by 1β-hydrogen abstraction at C1 of 19,19-dihydroxyandrostenedione, followed by homolytic cleavage of the C10-C19 bond with concurrent formation of a Δ1(10),4-3-ketosteroid and a C19 carbon radical, and terminated by oxygen rebound at C19.
AB - The article summarizes the results of recent studies on the metabolism of 10-ethylestr-4-ene-3,17-dione, 10-[(1R)-1-hydroxyethyl]-,and 10-[(1S)-1-hydroxyethyl]estr-4-ene-3, 17-dione, in placenta. These compounds are the 19-methyl analogs of androstenedione, 19-hydroxyandrostenedione, and 19-oxoandrostenedione, respectively. No conversion of 10-ethylestr-4-ene-3,17-dione to either estrogens or oxygenated metabolites was detected. Both 10-[(1R)-1-hydroxyethyl]- and 10-[(1S)-1-hydroxyethyl]estr-4-ene-3, 17-dione were oxygenated to 10-(1,1-dihydroxyethyl)estr-4-ene-3,17-dione and isolated following in situ dehydration as 10-acetylestr-4-ene-3,17-dione. Evidence for the involvement of aromatase in these conversions is discussed. No conversion of 10-acetylestr-4-ene-3,17-dione to either estrogens or other oxygenated products was detected. These results lead us to propose a new mechanism for the third aromatase monooxygenation. We propose that the third oxygenation is initiated by 1β-hydrogen abstraction at C1 of 19,19-dihydroxyandrostenedione, followed by homolytic cleavage of the C10-C19 bond with concurrent formation of a Δ1(10),4-3-ketosteroid and a C19 carbon radical, and terminated by oxygen rebound at C19.
UR - http://www.scopus.com/inward/record.url?scp=0023510939&partnerID=8YFLogxK
U2 - 10.1016/0039-128X(87)90025-0
DO - 10.1016/0039-128X(87)90025-0
M3 - Article
C2 - 3332933
AN - SCOPUS:0023510939
SN - 0039-128X
VL - 50
SP - 363
EP - 374
JO - Steroids
JF - Steroids
IS - 4-6
ER -