Abstract
Insulin and insulin like-growth factor-I (IGF-I) participate in the regulation of ovarian steroidogenesis. In insulin resistant states ovaries remain sensitive to insulin because insulin can activate alternative signaling pathways, such as phosphatidylinositol-3-kinase (PI-3 kinase) and mitogen-activated protein-kinase (MAPK) pathways, as well as insulin receptors and type 1 IGF receptors. We investigated the roles of MAPK-Erk1/2 and MAPK-p38 in insulin and IGF-I signaling pathways for progesterone production in human ovarian cells. Human ovarian cells were cultured in tissue culture medium in the presence of varying concentrations of insulin or IGF-I, with or without PD98059, a specific MAPK-Erk1/2 inhibitor, with or without SB203580, a specific MAPK-p38 inhibitor or with or without a specific PI-3-kinase inhibitor LY294002. Progesterone concentrations were measured using radioimmunoassay. PD98059 alone stimulated progesterone production in a dose-dependent manner by up to 65% (p<0.001). Similarly, LY294002 alone stimulated progesterone production by 1318% (p<0.005). However, when used together, PD98059 and LY294002 inhibited progesterone production by 1720% (p<0.001). SB203580 alone inhibited progesterone production by 2030% (p<0.001). Insulin or IGF-I alone stimulated progesterone production by 4060% (p<0.001). In insulin studies, PD98059 had no significant effect on progesterone synthesis while SB203580 abolished insulin-induced progesterone production. Either PD98059 or SB203580 abolished IGF-I-induced progesterone production. Both MAPK-Erk1/2 and MAPK-p38 participate in IGF-I-induced signaling pathways for progesterone production, while insulin-induced progesterone production requires MAPK-p38, but not MAPK-Erk1/2. These studies provide further evidence for divergence of insulin and IGF-I signaling pathways for human ovarian cell steroidogenesis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 386-390 |
| Number of pages | 5 |
| Journal | Hormone and Metabolic Research |
| Volume | 43 |
| Issue number | 6 |
| DOIs | |
| State | Published - 2011 |
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Keywords
- IGF-1
- insulin
- mitogen activated protein kinase
- polycystic ovary syndrome
- progesterone synthesis
- steroid hormones
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Clinical Biochemistry
- Biochemistry, medical
- Endocrinology, Diabetes and Metabolism
Cite this
Differential roles of MAPK-Erk1/2 and MAPK-p38 in insulin or insulin-like growth factor-I (IGF-I) signaling pathways for progesterone production in human ovarian cells. / Seto-Young, D.; Avtanski, D.; Varadinova, M.; Park, A.; Suwandhi, P.; Leiser, A.; Parikh, G.; Poretsky, L.
In: Hormone and Metabolic Research, Vol. 43, No. 6, 2011, p. 386-390.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential roles of MAPK-Erk1/2 and MAPK-p38 in insulin or insulin-like growth factor-I (IGF-I) signaling pathways for progesterone production in human ovarian cells
AU - Seto-Young, D.
AU - Avtanski, D.
AU - Varadinova, M.
AU - Park, A.
AU - Suwandhi, P.
AU - Leiser, A.
AU - Parikh, G.
AU - Poretsky, L.
PY - 2011
Y1 - 2011
N2 - Insulin and insulin like-growth factor-I (IGF-I) participate in the regulation of ovarian steroidogenesis. In insulin resistant states ovaries remain sensitive to insulin because insulin can activate alternative signaling pathways, such as phosphatidylinositol-3-kinase (PI-3 kinase) and mitogen-activated protein-kinase (MAPK) pathways, as well as insulin receptors and type 1 IGF receptors. We investigated the roles of MAPK-Erk1/2 and MAPK-p38 in insulin and IGF-I signaling pathways for progesterone production in human ovarian cells. Human ovarian cells were cultured in tissue culture medium in the presence of varying concentrations of insulin or IGF-I, with or without PD98059, a specific MAPK-Erk1/2 inhibitor, with or without SB203580, a specific MAPK-p38 inhibitor or with or without a specific PI-3-kinase inhibitor LY294002. Progesterone concentrations were measured using radioimmunoassay. PD98059 alone stimulated progesterone production in a dose-dependent manner by up to 65% (p<0.001). Similarly, LY294002 alone stimulated progesterone production by 1318% (p<0.005). However, when used together, PD98059 and LY294002 inhibited progesterone production by 1720% (p<0.001). SB203580 alone inhibited progesterone production by 2030% (p<0.001). Insulin or IGF-I alone stimulated progesterone production by 4060% (p<0.001). In insulin studies, PD98059 had no significant effect on progesterone synthesis while SB203580 abolished insulin-induced progesterone production. Either PD98059 or SB203580 abolished IGF-I-induced progesterone production. Both MAPK-Erk1/2 and MAPK-p38 participate in IGF-I-induced signaling pathways for progesterone production, while insulin-induced progesterone production requires MAPK-p38, but not MAPK-Erk1/2. These studies provide further evidence for divergence of insulin and IGF-I signaling pathways for human ovarian cell steroidogenesis.
AB - Insulin and insulin like-growth factor-I (IGF-I) participate in the regulation of ovarian steroidogenesis. In insulin resistant states ovaries remain sensitive to insulin because insulin can activate alternative signaling pathways, such as phosphatidylinositol-3-kinase (PI-3 kinase) and mitogen-activated protein-kinase (MAPK) pathways, as well as insulin receptors and type 1 IGF receptors. We investigated the roles of MAPK-Erk1/2 and MAPK-p38 in insulin and IGF-I signaling pathways for progesterone production in human ovarian cells. Human ovarian cells were cultured in tissue culture medium in the presence of varying concentrations of insulin or IGF-I, with or without PD98059, a specific MAPK-Erk1/2 inhibitor, with or without SB203580, a specific MAPK-p38 inhibitor or with or without a specific PI-3-kinase inhibitor LY294002. Progesterone concentrations were measured using radioimmunoassay. PD98059 alone stimulated progesterone production in a dose-dependent manner by up to 65% (p<0.001). Similarly, LY294002 alone stimulated progesterone production by 1318% (p<0.005). However, when used together, PD98059 and LY294002 inhibited progesterone production by 1720% (p<0.001). SB203580 alone inhibited progesterone production by 2030% (p<0.001). Insulin or IGF-I alone stimulated progesterone production by 4060% (p<0.001). In insulin studies, PD98059 had no significant effect on progesterone synthesis while SB203580 abolished insulin-induced progesterone production. Either PD98059 or SB203580 abolished IGF-I-induced progesterone production. Both MAPK-Erk1/2 and MAPK-p38 participate in IGF-I-induced signaling pathways for progesterone production, while insulin-induced progesterone production requires MAPK-p38, but not MAPK-Erk1/2. These studies provide further evidence for divergence of insulin and IGF-I signaling pathways for human ovarian cell steroidogenesis.
KW - IGF-1
KW - insulin
KW - mitogen activated protein kinase
KW - polycystic ovary syndrome
KW - progesterone synthesis
KW - steroid hormones
UR - http://www.scopus.com/inward/record.url?scp=79957823434&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79957823434&partnerID=8YFLogxK
U2 - 10.1055/s-0031-1273760
DO - 10.1055/s-0031-1273760
M3 - Article
C2 - 21448845
AN - SCOPUS:79957823434
VL - 43
SP - 386
EP - 390
JO - Hormone and Metabolic Research
JF - Hormone and Metabolic Research
SN - 0018-5043
IS - 6
ER -