help button home button Endocrine Society JCEM JCEM Call for Nominations for EIC
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
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 Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Erickson, G. F.
Right arrow Articles by Chang, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Erickson, G. F.
Right arrow Articles by Chang, R. J.

Journal of Clinical Endocrinology & Metabolism, Vol 70, 894-902, Copyright © 1990 by Endocrine Society


ARTICLES

The effects of insulin and insulin-like growth factors-I and -II on estradiol production by granulosa cells of polycystic ovaries

GF Erickson, DA Magoffin, JR Cragun and RJ Chang
Department of Reproductive Medicine, University of California-San Diego, La Jolla 92093.

The objective of this work was to examine the effects of insulin-like growth factors (IGFs) on estradiol (E2) production by granulosa cells obtained from ovaries of patients with polycystic ovary disease (PCO). Granulosa cells, isolated from ovaries of three PCO patients, were cultured in serum-free medium containing either androstenedione alone (10(-7) M) or androstenedione plus graded doses of FSH, IGF-I, IGF-II, and/or insulin. At the end of the culture period (2, 4, or 6 days) E2 levels in the medium were measured by RIA. The results from each patient were similar, and therefore, the data were pooled. In the 6-day time-course experiments, the control (untreated) cells produced relatively high levels of E2 at 2 days; however, none was detected thereafter. Treatment with FSH (30 ng/mL) stimulated E2 production 4- fold at 2 days, but the stimulatory effects of FSH were not sustained during culture. IGF-I at 30 ng/mL mimicked the effects of FSH. Concomitant treatment with FSH and IGF-I caused synergistic increases in E2 production (3-, 13-, and 33-fold at 2, 4, and 6 days, respectively). Dose-response studies revealed that FSH and IGF-I stimulated E2 production in a dose-dependent fashion (ED50 of FSH and IGF-I, were 1.1 +/- 0.3 and 7.6 +/- 7.2 ng/mL, respectively). In the presence of a maximally effective dose of FSH (30 ng/mL), the cells appeared to become more responsive to IGF-I (ED50 of IGF-I plus FSH, 1.09 +/- 0.29 ng/mL); however, this effect was not significant (P = 0.086). In the presence of a maximally effective dose of IGF-I (30 ng/mL), the stimulatory effect of FSH on E2 production was dramatically amplified, but the IGF-I did not significantly (P = 0.85) change the potency of FSH (ED50 of FSH plus IGF-I, 1.07 +/- 2.3 ng/mL). Treatment with IGF-II over the concentration range of 0.1-100 ng/mL had no effect on either control or FSH-stimulated E2 production. Treatment with insulin, either alone or together with FSH, increased the levels of E2, but the insulin effects were seen only at the highest doses tested (0.3- 10 micrograms/mL). The results in these in vitro experiments with PCO granulosa cells indicate that 1) physiological concentrations of IGF-I are as effective as FSH in stimulating E2 production; 2) IGF-I and FSH act synergistically to control the level of E2 production; and 3) this synergy was not observed with insulin or IGF-II.


This article has been cited by other articles:


Home page
J. Clin. Endocrinol. Metab.Home page
D. S. Wachs, M. S. Coffler, P. J. Malcom, S. Shimasaki, and R. J. Chang
Increased Androgen Response to Follicle-Stimulating Hormone Administration in Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1827 - 1833.
[Abstract] [Full Text] [PDF]


Home page
Biol. Reprod.Home page
L.J. Spicer and P.Y. Aad
Insulin-Like Growth Factor (IGF) 2 Stimulates Steroidogenesis and Mitosis of Bovine Granulosa Cells Through the IGF1 Receptor: Role of Follicle-Stimulating Hormone and IGF2 Receptor
Biol Reprod, July 1, 2007; 77(1): 18 - 27.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
J. Zhao, D.-H. Xiong, Y. Guo, T.-L. Yang, R. R. Recker, and H.-W. Deng
Polymorphism in the insulin-like growth factor 1 gene is associated with age at menarche in caucasian females
Hum. Reprod., June 1, 2007; 22(6): 1789 - 1794.
[Abstract] [Full Text] [PDF]


Home page
Eur J EndocrinolHome page
E. J P van Santbrink, F. P Hohmann, M. J C Eijkemans, J. S E Laven, and B. C J M Fauser
Does metformin modify ovarian responsiveness during exogenous FSH ovulation induction in normogonadotrophic anovulation? A placebo-controlled double-blind assessment
Eur. J. Endocrinol., April 1, 2005; 152(4): 611 - 617.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
G. A. R. Maciel, E. C. Baracat, J. A. Benda, S. M. Markham, K. Hensinger, R. J. Chang, and G. F. Erickson
Stockpiling of Transitional and Classic Primary Follicles in Ovaries of Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5321 - 5327.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
J. L. Phy, C. A. Conover, D. H. Abbott, M. A. Zschunke, D. L. Walker, D. R. Session, I. S. Tummon, A. R. Thornhill, T. G. Lesnick, and D. A. Dumesic
Insulin and Messenger Ribonucleic Acid Expression of Insulin Receptor Isoforms in Ovarian Follicles from Nonhirsute Ovulatory Women and Polycystic Ovary Syndrome Patients
J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3561 - 3566.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
M. S. Coffler, K. Patel, M. H. Dahan, R. Y. Yoo, P. J. Malcom, and R. J. Chang
Enhanced Granulosa Cell Responsiveness to Follicle-Stimulating Hormone during Insulin Infusion in Women with Polycystic Ovary Syndrome Treated with Pioglitazone
J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5624 - 5631.
[Abstract] [Full Text] [PDF]


Home page
Endocr. Rev.Home page
V. De Leo, A. la Marca, and F. Petraglia
Insulin-Lowering Agents in the Management of Polycystic Ovary Syndrome
Endocr. Rev., October 1, 2003; 24(5): 633 - 667.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
M. S. Coffler, K. Patel, M. H. Dahan, P. J. Malcom, T. Kawashima, R. Deutsch, and R. J. Chang
Evidence for Abnormal Granulosa Cell Responsiveness to Follicle-Stimulating Hormone in Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1742 - 1747.
[Abstract] [Full Text] [PDF]


Home page
Reproductive SciencesHome page
A. Shobokshi and M. Shaarawy
Correction of Insulin Resistance and Hyperandrogenism in Polycystic Ovary Syndrome By Combined Rosiglitazone and Clomiphene Citrate Therapy
Reproductive Sciences, February 1, 2003; 10(2): 99 - 104.
[Abstract] [PDF]


Home page
Biol. Reprod.Home page
T. R. Davidson, C. S. Chamberlain, T. S. Bridges, and L. J. Spicer
Effect of Follicle Size on In Vitro Production of Steroids and Insulin-Like Growth Factor (IGF)-I, IGF-II, and the IGF-Binding Proteins by Equine Ovarian Granulosa Cells
Biol Reprod, June 1, 2002; 66(6): 1640 - 1648.
[Abstract] [Full Text] [PDF]


Home page
Hum ReprodHome page
P. Fedorcsak, P. O. Dale, R. Storeng, T. Tanbo, and T. Abyholm
The impact of obesity and insulin resistance on the outcome of IVF or ICSI in women with polycystic ovarian syndrome
Hum. Reprod., June 1, 2001; 16(6): 1086 - 1091.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
D. J. Jakubowicz, M. Seppälä, S. Jakubowicz, O. Rodriguez-Armas, A. Rivas-Santiago, H. Koistinen, R. Koistinen, and J. E. Nestler
Insulin Reduction with Metformin Increases Luteal Phase Serum Glycodelin and Insulin-Like Growth Factor-Binding Protein 1 Concentrations and Enhances Uterine Vascularity and Blood Flow in the Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1126 - 1133.
[Abstract] [Full Text]


Home page
Hum ReprodHome page
V. De Leo, A. la Marca, G. Morgante, L. Ciotta, L. Mencaglia, A. Cianci, and F. Petraglia
Clomiphene citrate increases insulin-like growth factor binding protein-1 and reduces insulin-like growth factor-I without correcting insulin resistance associated with polycystic ovarian syndrome
Hum. Reprod., November 1, 2000; 15(11): 2302 - 2305.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
V. De Leo, A. la Marca, R. Orvieto, and G. Morgante
Effect of Metformin on Insulin-Like Growth Factor (IGF) I and IGF-Binding Protein I in Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1598 - 1600.
[Abstract] [Full Text]


Home page
Endocr. Rev.Home page
L. Poretsky, N. A. Cataldo, Z. Rosenwaks, and L. C. Giudice
The Insulin-Related Ovarian Regulatory System in Health and Disease
Endocr. Rev., August 1, 1999; 20(4): 535 - 582.
[Abstract] [Full Text] [PDF]


Home page
Mol. Endocrinol.Home page
V. L. Nelson, R. S. Legro, J. F. Strauss III, and J. M. McAllister
Augmented Androgen Production Is a Stable Steroidogenic Phenotype of Propagated Theca Cells from Polycystic Ovaries
Mol. Endocrinol., June 1, 1999; 13(6): 946 - 957.
[Abstract] [Full Text]


Home page
Hum ReprodHome page
C.S. Wright, O. Hovatta, R. Margara, G. Trew, R.M.L. Winston, S. Franks, and K. Hardy
Effects of follicle-stimulating hormone and serum substitution on the in-vitro growth of human ovarian follicles
Hum. Reprod., June 1, 1999; 14(6): 1555 - 1562.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
T. M. Fiad, T. P. Smith, S. K. Cunningham, and T. J. McKenna
Decline in Insulin-Like Growth Factor I Levels after Clomiphene Citrate Does Not Correct Hyperandrogenemia in Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., July 1, 1998; 83(7): 2394 - 2398.
[Abstract] [Full Text]


Home page
J. Clin. Endocrinol. Metab.Home page
J. E. Nestler and D. J. Jakubowicz
Lean Women with Polycystic Ovary Syndrome Respond to Insulin Reduction with Decreases in Ovarian P450c17{alpha} Activity and Serum Androgens
J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 4075 - 4079.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
A. M. Fulghesu, P. Villa, V. Pavone, M. Guido, R. Apa, A. Caruso, A. Lanzone, A. Rossodivita, and S. Mancuso
The Impact of Insulin Secretion on the Ovarian Response to Exogenous Gonadotropins in Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., February 1, 1997; 82(2): 644 - 648.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1990 by The Endocrine Society