Biol Reprod Lalor Postdoctoral Fellowships -- Application Deadline January 15, 2009
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

BOR - Papers in Press, published online ahead of print February 15, 2006.
Biol Reprod 2006, 10.1095/biolreprod.105.049908
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
74/6/1034    most recent
biolreprod.105.049908v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kwintkiewicz, J.
Right arrow Articles by Duleba, A. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kwintkiewicz, J.
Right arrow Articles by Duleba, A. J.
Agricola
Right arrow Articles by Kwintkiewicz, J.
Right arrow Articles by Duleba, A. J.
BIOLOGY OF REPRODUCTION 74, 1034–1040 (2006)
DOI: 10.1095/biolreprod.105.049908
© 2006 by the Society for the Study of Reproduction, Inc.

Research Article

Insulin and Oxidative Stress Modulate Proliferation of Rat Ovarian Theca-Interstitial Cells Through Diverse Signal Transduction Pathways1

Jakub Kwintkiewicz 3, Robert Z. Spaczynski 4, Nastaran Foyouzi 3, Tugce Pehlivan 5, and Antoni J. Duleba 2 3

Department of Obstetrics and Gynecology,3 Yale University School of Medicine, New Haven, Connecticut 06510 Department of Gynecology and Obstetrics,4 Poznan University of Medical Sciences, 60-535 Poznan, Poland Instituto Valenciano de Infertilidad,5 46015 Valencia, Spain

ABSTRACT

Insulin and moderate oxidative stress stimulate proliferation of ovarian theca-interstitial cells. The effects of these agents on selected signal transduction pathways were examined. PD98059 (inhibitor of MAP2K1, also known as MEK-1, upstream of extracellular signal-regulated protein kinases MAPK3/1, also known as ERK1/2), wortmannin (inhibitor of PIK3C2A, also known as PI3K), and rapamycin (inhibitor of FRAP1, also known as mTOR, upstream of RPS6KB1) each significantly decreased insulin and oxidative stress-induced proliferation of theca-interstitial cells. The greatest inhibition was observed in the presence of rapamycin; this effect occurred without a significant change in cell viability. Phosphorylation of AKT was stimulated by insulin only, while phosphorylation of MAPK3/1 and RPS6KB1 was increased by insulin and oxidative stress. Insulin-induced and oxidative stress-induced phosphorylation of RPS6KB1 was partly inhibited by wortmannin and partly by PD98059; the greatest inhibition was observed in the presence of a combination of wortmannin plus PD98059. Effects of insulin and oxidative stress on phosphorylation of RPS6KB1 were confirmed by kinase activity assays. These findings indicate that actions of insulin and oxidative stress converge on MAPK3/1 and RPS6KB1. Furthermore, we speculate that activation of RPS6KB1 may be in part induced via the MAPK3/1 pathway.

IGF1, insulin, oxidative stress, signal transduction, theca cells

FOOTNOTES

1 Supported by NIH grant R01 HD40207 to A.J.D.

2 Correspondence: Antoni J. Duleba, Yale University School of Medicine, Department of Obstetrics and Gynecology, 333 Cedar St., New Haven, CT 06510. FAX: 203 785 7134;

101 antoni.duleba{at}yale.edu






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the Society for the Study of Reproduction.