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

D. Seto-Young, D. Avtanski, M. Varadinova, A. Park, P. Suwandhi, A. Leiser, G. Parikh, L. Poretsky

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)386-390
Number of pages5
JournalHormone and Metabolic Research
Volume43
Issue number6
DOIs
StatePublished - 2011

Fingerprint

Mitogen-Activated Protein Kinase 1
p38 Mitogen-Activated Protein Kinases
Insulin-Like Growth Factor I
Progesterone
Insulin
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Phosphatidylinositol 3-Kinase
Tissue culture
IGF Type 1 Receptor
Insulin Receptor
Protein Kinase Inhibitors
Mitogen-Activated Protein Kinases
Phosphatidylinositol 3-Kinases
Radioimmunoassay
Culture Media
Ovary
Cultured Cells
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

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 journalArticle

Seto-Young, D. ; Avtanski, D. ; Varadinova, M. ; Park, A. ; Suwandhi, P. ; Leiser, A. ; Parikh, G. ; Poretsky, L. / 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. In: Hormone and Metabolic Research. 2011 ; Vol. 43, No. 6. pp. 386-390.
@article{8546e859c7dd47feb6a30023e0dde792,
title = "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",
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.",
keywords = "IGF-1, insulin, mitogen activated protein kinase, polycystic ovary syndrome, progesterone synthesis, steroid hormones",
author = "D. Seto-Young and D. Avtanski and M. Varadinova and A. Park and P. Suwandhi and A. Leiser and G. Parikh and L. Poretsky",
year = "2011",
doi = "10.1055/s-0031-1273760",
language = "English (US)",
volume = "43",
pages = "386--390",
journal = "Hormone and Metabolic Research",
issn = "0018-5043",
publisher = "Georg Thieme Verlag",
number = "6",

}

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 -