TY - JOUR
T1 - The effect of transforming growth factor-β on steroidogenesis and expression of key steroidogenic enzymes with a human ovarian thecal-like tumor cell model
AU - Carr, B. R.
AU - McGee, E. A.
AU - Sawetawan, C.
AU - Clyne, C. D.
AU - Rainey, W. E.
AU - Weiss, G.
AU - Jaffe, R. B.
AU - Hill, J. A.
PY - 1996/1/1
Y1 - 1996/1/1
N2 - OBJECTIVE: Our purpose was to determine the effects of transforming growth factor-β on steroidogenesis and regulation of steroidogenic enzyme expression by use of a human ovarian thecal-like tumor cell culture system. STUDY DESIGN: Human ovarian thecal-like tumor cells were treated in serum- free medium in the presence or absence of forskolin and transforming growth factor-β1. The accumulation of progesterone and androstenedione in the culture medium was evaluated by radioimmunoassay. The effects of forskolin with or without transforming growth factor-β1 on the enzymatic activity of P450c17 and 3βHSD, the expression of immunodetectable P450c17 protein, and the expression of messenger ribonucleic acid for P450scc, P450c17, and 3βHSD were determined. RESULTS: Basal steroid secretion, steroidogenic enzyme activity, enzyme protein, and messenger ribonucleic acid expression were not affected by transforming growth factor-β1 alone. Forskolin treatment significantly stimulated steroid production and the enzymatic activity of P450c17 and 3βHSD up to 10-fold above basal levels. However, transforming growth factor-β1 inhibited forskolin-stimulated androstenedione production to near basal levels and increased progesterone 1.4- to 2-fold while suppressing P450c17 enzyme activity to near basal levels, but it did not affect 3βHSD activity. Forskolin stimulated immunodetectable P450c17α protein was markedly inhibited by transforming growth factor-β1. In addition, transforming growth factor-β1 markedly inhibited the forskolin- stimulation of P450c17 messenger ribonucleic acid, while not significantly altering P450scc or 3βHSD messenger ribonucleic acid expression. CONCLUSION: Forskolin stimulated human ovarian thecal-like tumor cell steroidogenesis, P450c17 and 3βHSD activity, immunodetectable P450c17, and messenger ribonucleic acid content for P450scc, P450c17, and 3βHSD. Transforming growth factor-β1 inhibited forskolin stimulation of androstenedione production through the inhibition of P450c17 expression.
AB - OBJECTIVE: Our purpose was to determine the effects of transforming growth factor-β on steroidogenesis and regulation of steroidogenic enzyme expression by use of a human ovarian thecal-like tumor cell culture system. STUDY DESIGN: Human ovarian thecal-like tumor cells were treated in serum- free medium in the presence or absence of forskolin and transforming growth factor-β1. The accumulation of progesterone and androstenedione in the culture medium was evaluated by radioimmunoassay. The effects of forskolin with or without transforming growth factor-β1 on the enzymatic activity of P450c17 and 3βHSD, the expression of immunodetectable P450c17 protein, and the expression of messenger ribonucleic acid for P450scc, P450c17, and 3βHSD were determined. RESULTS: Basal steroid secretion, steroidogenic enzyme activity, enzyme protein, and messenger ribonucleic acid expression were not affected by transforming growth factor-β1 alone. Forskolin treatment significantly stimulated steroid production and the enzymatic activity of P450c17 and 3βHSD up to 10-fold above basal levels. However, transforming growth factor-β1 inhibited forskolin-stimulated androstenedione production to near basal levels and increased progesterone 1.4- to 2-fold while suppressing P450c17 enzyme activity to near basal levels, but it did not affect 3βHSD activity. Forskolin stimulated immunodetectable P450c17α protein was markedly inhibited by transforming growth factor-β1. In addition, transforming growth factor-β1 markedly inhibited the forskolin- stimulation of P450c17 messenger ribonucleic acid, while not significantly altering P450scc or 3βHSD messenger ribonucleic acid expression. CONCLUSION: Forskolin stimulated human ovarian thecal-like tumor cell steroidogenesis, P450c17 and 3βHSD activity, immunodetectable P450c17, and messenger ribonucleic acid content for P450scc, P450c17, and 3βHSD. Transforming growth factor-β1 inhibited forskolin stimulation of androstenedione production through the inhibition of P450c17 expression.
KW - human ovarian thecal-like tumor cell
KW - steroidogenesis
KW - Transforming growth factor
UR - http://www.scopus.com/inward/record.url?scp=0029920658&partnerID=8YFLogxK
U2 - 10.1016/S0002-9378(96)70652-X
DO - 10.1016/S0002-9378(96)70652-X
M3 - Article
C2 - 8623837
AN - SCOPUS:0029920658
SN - 0002-9378
VL - 174
SP - 1109
EP - 1117
JO - American Journal of Obstetrics and Gynecology
JF - American Journal of Obstetrics and Gynecology
IS - 4
ER -