Endocrinology, Vol 122, 1583-1591, Copyright © 1988 by Endocrine Society

ARTICLES

Insulin-like growth factor-I as an amplifier of follicle-stimulating hormone action: studies on mechanism(s) and site(s) of action in cultured rat granulosa cells

EY Adashi, CE Resnick, ER Hernandez, JV May, M Knecht, ME Svoboda and JJ Van Wyk
Department of Obstetrics/Gynecology, University of Maryland School of Medicine, Baltimore 21201.

The ovarian granulosa cell has recently been shown to be a site of insulin-like growth factor-I (IGF-I) production, reception, and action. In large measure, IGF-I action (in the rat) appears contingent upon its ability to synergize with FSH, a major promoter of granulosa cell differentiation. It is the objective of the in vitro studies reported herein to elucidate the cellular mechanism(s) whereby IGF-I amplifies FSH hormonal action, placing special emphasis on the potential role of the putative intracellular second messenger cAMP in this regard. Basal FSH binding (115.7 +/- 2.1 fmol/mg cell protein) to rat granulosa cells cultured under serum-free conditions remained unchanged after 72 h of treatment with IGF-I (50 ng/ml) by itself (107.1 +/- 1.0 fmol/mg cell protein). In contrast, treatment with FSH (20 ng/ml) resulted in a significant (P less than 0.05) decrease in FSH binding capacity (but not affinity) relative to controls in either the absence or presence of IGF-I. Whereas treatment with FSH resulted in a substantial increase in forskolin-stimulatable adenylate cyclase activity (10 +/- 1.7% conversion of [3H] ATP to [3H]cAMP), concurrent treatment with IGF-I resulted in 2.2-fold enhancement of FSH action. This IGF-I effect proved dose dependent with an apparent median effective dose of 3.6 +/- 0.8 ng/ml, a concentration in keeping with its granulosa cell receptor binding affinity. Significantly, however, IGF-I proved capable of enhancing Bt2cAMP-stimulated progesterone accumulation suggesting that IGF-I may be also acting at site(s) distal to cAMP generation. Taken together, these and previous studies indicate that nanomolar concentrations of exogenously added IGF-I may be interacting with the FSH transduction signal at multiple cellular site(s) to effect amplification of FSH action.

This article has been cited by other articles:

				L. Nemcova, E. Nagyova, M. Petlach, M. Tomanek, and R. Prochazka Molecular Mechanisms of Insulin-Like Growth Factor 1 Promoted Synthesis and Retention of Hyaluronic Acid in Porcine Oocyte-Cumulus Complexes Biol Reprod, June 1, 2007; 76(6): 1016 - 1024. [Abstract] [Full Text] [PDF]

				M.L. Hendriks, J.C.F. Ket, P.G.A. Hompes, R. Homburg, and C.B. Lambalk Why does ovarian surgery in PCOS help? Insight into the endocrine implications of ovarian surgery for ovulation induction in polycystic ovary syndrome Hum. Reprod. Update, May 1, 2007; 13(3): 249 - 264. [Abstract] [Full Text] [PDF]

				S. Eimerl and J. Orly Regulation of Steroidogenic Genes by Insulin-Like Growth Factor-1 and Follicle-Stimulating Hormone: Differential Responses of Cytochrome P450 Side-Chain Cleavage, Steroidogenic Acute Regulatory Protein, and 3{beta}-Hydroxysteroid Dehydrogenase/Isomerase in Rat Granulosa Cells Biol Reprod, September 1, 2002; 67(3): 900 - 910. [Abstract] [Full Text] [PDF]

				R. J. Zachow and J. K. Woolery Effects of Hepatocyte Growth Factor on Cyclic Nucleotide-Dependent Signaling and Steroidogenesis in Rat Ovarian Granulosa Cells In Vitro Biol Reprod, August 1, 2002; 67(2): 454 - 459. [Abstract] [Full Text] [PDF]

				P. Froment, D. Seurin, S. Hembert, J. E. Levine, C. Pisselet, D. Monniaux, M. Binoux, and P. Monget Reproductive Abnormalities in Human IGF Binding Protein-1 Transgenic Female Mice Endocrinology, May 1, 2002; 143(5): 1801 - 1808. [Abstract] [Full Text] [PDF]

				M. M. M. Woo, C.-J. Tai, S. K. Kang, P. S. Nathwani, S. F. Pang, and P. C. K. Leung Direct Action of Melatonin in Human Granulosa-Luteal Cells J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4789 - 4797. [Abstract] [Full Text] [PDF]

				N. Kikuchi, K. Andoh, Y. Abe, K. Yamada, H. Mizunuma, and Y. Ibuki Inhibitory Action of Leptin on Early Follicular Growth Differs in Immature and Adult Female Mice Biol Reprod, July 1, 2001; 65(1): 66 - 71. [Abstract] [Full Text] [PDF]

				P. F. Backeljauw and L. E. Underwood Therapy for 6.5-7.5 Years with Recombinant Insulin-Like Growth Factor I in Children with Growth Hormone Insensitivity Syndrome: A Clinical Research Center Study J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1504 - 1510. [Abstract] [Full Text]

				I. J. Gonzalez-Robayna, A. E. Falender, S. Ochsner, G. L. Firestone, and J. S. Richards Follicle-Stimulating Hormone (FSH) Stimulates Phosphorylation and Activation of Protein Kinase B (PKB/Akt) and Serum and Glucocorticoid-Induced Kinase (Sgk): Evidence for A Kinase-Independent Signaling by FSH in Granulosa Cells Mol. Endocrinol., August 1, 2000; 14(8): 1283 - 1300. [Abstract] [Full Text]

				T. Hirakawa, T. Minegishi, K. Abe, H. Kishi, Y. Ibuki, and K. Miyamoto A Role of Insulin-Like Growth Factor I in Luteinizing Hormone Receptor Expression in Granulosa Cells Endocrinology, November 1, 1999; 140(11): 4965 - 4971. [Abstract] [Full Text]

				L. Devoto, L. K. Christenson, J. M. McAllister, A. Makrigiannakis, and J. F. Strauss III Insulin and insulin-like growth factor-I and- II modulate human granulosa-lutein cell steroidogenesis: enhancement of steroidogenic acute regulatory protein (StAR) expression Mol. Hum. Reprod., November 1, 1999; 5(11): 1003 - 1010. [Abstract] [Full Text] [PDF]

				H. A. LaVoie, J. C. Garmey, and J. D. Veldhuis Mechanisms of Insulin-Like Growth Factor I Augmentation of Follicle-Stimulating Hormone-Induced Porcine Steroidogenic Acute Regulatory Protein Gene Promoter Activity in Granulosa Cells Endocrinology, January 1, 1999; 140(1): 146 - 153. [Abstract] [Full Text]

				H. A. LaVoie, J. C. Garmey, R. N. Day, and J. D. Veldhuis Concerted Regulation of Low Density Lipoprotein Receptor Gene Expression by Follicle-Stimulating Hormone and Insulin-Like Growth Factor I in Porcine Granulosa Cells: Promoter Activation, Messenger Ribonucleic Acid Stability, and Sterol Feedback Endocrinology, January 1, 1999; 140(1): 178 - 186. [Abstract] [Full Text]

				S. Azhar, A. Nomoto, S. Leers-Sucheta, and E. Reaven Simultaneous induction of an HDL receptor protein (SR-BI) and the selective uptake of HDL-cholesteryl esters in a physiologically relevant steroidogenic cell model J. Lipid Res., August 1, 1998; 39(8): 1616 - 1628. [Abstract] [Full Text]

				E. Y. Adashi Insulin-Like Growth Factors as Determinants of Follicular Fate Reproductive Sciences, November 1, 1995; 2(6): 721 - 726. [Abstract] [PDF]