TY - JOUR
T1 - Regulation of aromatase activity of cultured adipose stromal cells by catecholamines and adrenocorticotropin
AU - Mendelson, Carole R.
AU - Smith, Margaret E.
AU - Cleland, William H.
AU - Simpson, Evan R.
N1 - Funding Information:
The authors gratefully acknowledge the technical assistance of Ms. Karen Kacir and Ms. Janet Smith and the editorial assistance of Ms. Darlene Tutton and Ms. Sylvia Williams. Zinterol and metoprolol were generous gifts of Dr. John Bleas-dale, Department of Biochemistry. Antiserum raised against succinyl cyclic AMP-BSA was a generous gift of Dr. Maria Dufau, National Institutes of Health. This research was supported, in part, by USPHS Grants AG-00316 and AM-31206.
Funding Information:
31206. W.H.C. was a postdoctoral trainee supported, in part, by USPHS Training Grant l-T32-HD-07190.
PY - 1984/8
Y1 - 1984/8
N2 - Adipose tissue is the major site of estrogen formation in postmenopausal women. We have previously reported (Simpson E.R., Ackerman G.E., Smith M.E. and Mendelson C.R. (1981) Proc. Natl. Acad. Sci. (U.S.A.) 78, 5690-5694; Mendelson C.R., Cleland W.H., Smith M.E. and Simpson E.R. (1982) Endocrinology 111, 1077-1085) that aromatase activity of human adipose stromal cells in culture is stimulated by glucocorticoids and by dibutyryl cyclic AMP (Bt2-cAMP). In order to establish which physiological factors might stimulate aromatase activity of these cells by activation of adenylate cyclase, we have investigated the roles of adrenocorticotropin (ACTH) and isoproterenol to increase cyclic AMP levels and stimulate the aromatization of androstenedione. In the presence of methylisobutylxanthine (MIX), ACTH stimulated cyclic AMP formation and aromatase activity in a time- and concentration-dependent manner. The concentration of ACTH required for half-maximal stimulation was ~ 10-8 M. Isoproterenol, in the presence of MIX, stimulated cyclic AMP formation in a time- and concentration-dependent fashion, and also stimulated aromatase activity. These effects of isoproterenol appeared to be mediated by binding of the agonist to a population of β-adrenergic receptors. On the basis of these and our previous studies, we suggest that ACTH may play an important role in stimulating estrogen formation by human adipose tissue, both directly, and by stimulating the adrenal cortex to produce both substrate, androstenedione, and inducing agent, namely cortisol.
AB - Adipose tissue is the major site of estrogen formation in postmenopausal women. We have previously reported (Simpson E.R., Ackerman G.E., Smith M.E. and Mendelson C.R. (1981) Proc. Natl. Acad. Sci. (U.S.A.) 78, 5690-5694; Mendelson C.R., Cleland W.H., Smith M.E. and Simpson E.R. (1982) Endocrinology 111, 1077-1085) that aromatase activity of human adipose stromal cells in culture is stimulated by glucocorticoids and by dibutyryl cyclic AMP (Bt2-cAMP). In order to establish which physiological factors might stimulate aromatase activity of these cells by activation of adenylate cyclase, we have investigated the roles of adrenocorticotropin (ACTH) and isoproterenol to increase cyclic AMP levels and stimulate the aromatization of androstenedione. In the presence of methylisobutylxanthine (MIX), ACTH stimulated cyclic AMP formation and aromatase activity in a time- and concentration-dependent manner. The concentration of ACTH required for half-maximal stimulation was ~ 10-8 M. Isoproterenol, in the presence of MIX, stimulated cyclic AMP formation in a time- and concentration-dependent fashion, and also stimulated aromatase activity. These effects of isoproterenol appeared to be mediated by binding of the agonist to a population of β-adrenergic receptors. On the basis of these and our previous studies, we suggest that ACTH may play an important role in stimulating estrogen formation by human adipose tissue, both directly, and by stimulating the adrenal cortex to produce both substrate, androstenedione, and inducing agent, namely cortisol.
KW - adipose tissue
KW - estrogen formation
KW - postmenopausal women
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U2 - 10.1016/0303-7207(84)90128-X
DO - 10.1016/0303-7207(84)90128-X
M3 - Article
C2 - 6205918
AN - SCOPUS:0021261088
SN - 0303-7207
VL - 37
SP - 61
EP - 72
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1
ER -