Journal of Clinical Endocrinology & Metabolism, Vol 76, 207-215, Copyright © 1993 by Endocrine Society

ARTICLES

Regulation of insulin-like growth factor binding protein production by human luteinizing granulosa cells cultured in defined medium

NA Cataldo, TK Woodruff and LC Giudice
Department of Gynecology and Obstetrics, Stanford University Medical Center, California 94305.

The production of insulin-like growth factor (IGF) binding proteins (IGFBPs) by human luteinizing granulosa cells obtained at oocyte harvest for in vitro fertilization was studied in defined medium. Three species of IGFBP were noted on Western ligand blotting of conditioned medium. A 31-33 kilodalton (kDa) doublet identified as IGFBP-2 by immunoprecipitation was consistently seen and was shown by metabolic labeling to be synthesized de novo. IGFBP-2 production was inhibited by hCG (100 ng/mL) to 32 +/- 8% of levels in control cultures; a similar inhibition was seen with dibutyryl cAMP and forskolin, but not with FSH. IGFBP-2 production was also inhibited by IGF-II and [Leu27]IGF-II (ED50 for both 3 ng/mL) but not by IGF-I at up to 30 ng/mL. In addition to IGFBP-2, a 35-45 kDa IGFBP identified by immunoprecipitation as IGFBP-3 was variably present on ligand blots of control conditioned medium and was consistently found in medium from cells treated with IGF- I or IGF-II (ED50 3 ng/mL) but not with insulin at 2 mg/mL. No de novo synthesis of IGFBP-3 was noted, suggesting that IGFBP-3 may be released from the cell surface by ligand. A 24-kDa IGFBP consistent with IGFBP-4 was also variably noted in basal cultures. Since IGFBPs are believed to sequester IGF peptides and inhibit their action on the granulosa, control of IGFBP production may be an important step in regulating gonadotropin and IGF action in the human granulosa cell.

This article has been cited by other articles:

				C. N. Harvey, M. Esmail, Q. Wang, A. I. Brooks, R. Zachow, and M. Uzumcu Effect of the Methoxychlor Metabolite HPTE on the Rat Ovarian Granulosa Cell Transcriptome In Vitro Toxicol. Sci., July 1, 2009; 110(1): 95 - 106. [Abstract] [Full Text] [PDF]

				S. Perlman, T. Bouquin, B. van den Hazel, T.H. Jensen, H.T. Schambye, S. Knudsen, and J.S. Okkels Transcriptome analysis of FSH and FSH variant stimulation in granulosa cells from IVM patients reveals novel regulated genes Mol. Hum. Reprod., March 1, 2006; 12(3): 135 - 144. [Abstract] [Full Text] [PDF]

				R. J. Wright, J. M.P. Holly, R. Galea, M. Brincat, and H. D. Mason Insulin-Like Growth Factor (IGF)-Independent Effects of IGF Binding Protein-4 on Human Granulosa Cell Steroidogenesis Biol Reprod, September 1, 2002; 67(3): 776 - 781. [Abstract] [Full Text] [PDF]

				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]

				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]

				S. Azhar, L. Tsai, S. Medicherla, Y. Chandrasekher, L. Giudice, and E. Reaven Human Granulosa Cells Use High Density Lipoprotein Cholesterol for Steroidogenesis J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 983 - 991. [Abstract] [Full Text]

				N. A. Cataldo, V. Y. Fujimoto, and R. B. Jaffe Interferon-{gamma} and Activin A Promote Insulin-Like Growth Factor-Binding Protein-2 and -4 Accumulation by Human Luteinizing Granulosa Cells, and Interferon-{gamma} Promotes Their Apoptosis J. Clin. Endocrinol. Metab., January 1, 1998; 83(1): 179 - 186. [Abstract] [Full Text]

				J. Rabinovici, N. A. Cataldo, P. Dandekar, S. M. Rosenthal, S. E. Gargosky, N. Gesundheit, and M. C. Martin Adjunctive Growth Hormone during Ovarian Hyperstimulation Increases Levels of Insulin-Like Growth Factor Binding Proteins in Follicular Fluid: A Randomized, Placebo-Controlled, Cross-Over Study J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1171 - 1176. [Abstract] [Full Text] [PDF]