TY - JOUR
T1 - Sulfation of tibolone metabolites by human postmenopausal liver and small intestinal sulfotransferases (SULTs)
AU - Wang, Min
AU - Ebmeier, Christopher C.
AU - Olin, John R.
AU - Anderson, Robert J.
N1 - Funding Information:
This work was supported by a grant from N.V. Organon Inc. and the VA Medical Research Service.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/5
Y1 - 2006/5
N2 - Sulfation is a major pathway in humans for the biotransformation of steroid hormones and structurally related therapeutic agents. Tibolone is a synthetic steroid used for the treatment for climacteric symptoms and postmenopausal osteoporosis. Sulfation inactivates the hydroxylated metabolites, 3α-hydroxytibolone (3α-OH-tibolone) and 3β-hydroxytibolone (3β-OH-tibolone), and contributes to the regulation of tissue responses to tibolone. We detected SULT1A1, SULT1A3, SULT1E1 and SULT2A1 mRNA expression by RT-PCR in postmenopausal liver and small intestine. Liver pool (n = 5) SULT activities measured with tibolone substrates reflected COS-1 expressed SULT2A1 and SULT1E1 activities. Liver SULT2A1 activity (1.8 ± 0.3 units/mg protein, n = 8, mean ± SEM), and activities with 3α-OH-tibolone (0.6 ± 0.1, n = 8) and 3β-OH-tibolone (0.9 ± 0.2, n = 8) were higher than SULT1E1 activities (
AB - Sulfation is a major pathway in humans for the biotransformation of steroid hormones and structurally related therapeutic agents. Tibolone is a synthetic steroid used for the treatment for climacteric symptoms and postmenopausal osteoporosis. Sulfation inactivates the hydroxylated metabolites, 3α-hydroxytibolone (3α-OH-tibolone) and 3β-hydroxytibolone (3β-OH-tibolone), and contributes to the regulation of tissue responses to tibolone. We detected SULT1A1, SULT1A3, SULT1E1 and SULT2A1 mRNA expression by RT-PCR in postmenopausal liver and small intestine. Liver pool (n = 5) SULT activities measured with tibolone substrates reflected COS-1 expressed SULT2A1 and SULT1E1 activities. Liver SULT2A1 activity (1.8 ± 0.3 units/mg protein, n = 8, mean ± SEM), and activities with 3α-OH-tibolone (0.6 ± 0.1, n = 8) and 3β-OH-tibolone (0.9 ± 0.2, n = 8) were higher than SULT1E1 activities (
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U2 - 10.1016/j.steroids.2005.11.003
DO - 10.1016/j.steroids.2005.11.003
M3 - Article
C2 - 16360722
AN - SCOPUS:33646074319
VL - 71
SP - 343
EP - 351
JO - Steroids
JF - Steroids
SN - 0039-128X
IS - 5
ER -