Endocrinology, Vol 130, 625-636, Copyright © 1992 by Endocrine Society

ARTICLES

Cyclic changes in insulin-like growth factor-binding protein-4 messenger ribonucleic acid in the rat ovary [published erratum appears in Endocrinology 1992 Nov;131(5):2350]

GF Erickson, A Nakatani, N Ling and S Shimasaki
Department of Reproductive Medicine, University of California-San Diego, La Jolla 92093-0625.

We have previously shown that the mRNA for insulin-like growth factor- binding protein-4 (IGFBP-4) is present in adult rat ovaries, being localized predominantly to granulosa cells of atretic follicles. Now we have considered the following questions. What class of atretic follicles expresses IGFBP-4 mRNA? How does IGFBP-4 mRNA expression change during the estrous cycle? In keeping with our earlier work, a strong hybridization signal for IGFBP-4 mRNA was present in subpopulations of follicles throughout the estrous cycle. In all cases, the hybridization signal was localized to granulosa cells. Among the various types of follicles, IGFBP-4 mRNA was present almost exclusively in atretic graafian (antral) follicles. Morphologically, the outer layer of granulosa cells was positive, while cells in the cumulus oophorous were negative. By Northern analysis and in situ hybridization, the levels of IGFBP-4 mRNA were found to change over the estrous cycle. At 1000 h on proestrus (before the LH/FSH surge), the hybridization signal was relatively weak, being restricted in some (but not all) atretic Graafian follicles. At 2000 h on proestrus, (after the LH/FSH surge), essentially all atretic Graafian follicles were strongly positive for the message. The pattern of hybridization was similar at 0200 h on estrus, but the signal was less intense. At 1000 h on estrus, the hybridization signal was variable, ranging from very strong to weak or undetectable in atretic follicles. At this stage, however, the highest levels of IGFBP-4 mRNA were measured by Northern analysis; interestingly, a strong signal became apparent in the stromal cells. On diestrous day 1, the message levels decreased, and the signal was restricted to some atretic follicles. On diestrous day 2, the hybridization signal was very weak. There was virtually no detectable IGFBP-4 mRNA in any healthy follicle. In summary, we found that IGFBP-4 mRNA is 1) not detected in healthy dominant follicles; 2) localized almost exclusively to atretic Graafian follicles, except on estrus when it also appears in stromal cells; 3) localized predominantly to the mural granulosa cells in atretic follicles; and 4) undergoes changes during the cycle, being most prominent around estrous morning. The possibility that IGFBP-4 plays a role in the cyclic destruction of cohort Graafian follicles at estrus, perhaps by mechanisms involving hormones, is discussed.

This article has been cited by other articles:

				T. Pakarainen, F.-P. Zhang, L. Nurmi, M. Poutanen, and I. Huhtaniemi Knockout of Luteinizing Hormone Receptor Abolishes the Effects of Follicle-Stimulating Hormone on Preovulatory Maturation and Ovulation of Mouse Graafian Follicles Mol. Endocrinol., October 1, 2005; 19(10): 2591 - 2602. [Abstract] [Full Text] [PDF]

				M. Matsui, B. Sonntag, S. S. Hwang, T. Byerly, A. Hourvitz, E. Y. Adashi, S. Shimasaki, and G. F. Erickson Pregnancy-Associated Plasma Protein-A Production in Rat Granulosa Cells: Stimulation by Follicle-Stimulating Hormone and Inhibition by the Oocyte-Derived Bone Morphogenetic Protein-15 Endocrinology, August 1, 2004; 145(8): 3686 - 3695. [Abstract] [Full Text] [PDF]

				D. Chamoun, D. Choi, A. B. Tavares, L. C. Udoff, E. Levitas, C. E. Resnick, R. G. Rosenfeld, and E. Y. Adashi Regulation of Granulosa Cell-Derived Insulin-Like Growth Factor Binding Proteins (IGFBPs): Role for Protein Kinase-C in the Pre- and Posttranslational Modulation of IGFBP-4 and IGFBP-5 Biol Reprod, September 1, 2002; 67(3): 1003 - 1012. [Abstract] [Full Text] [PDF]

				A. Hourvitz, A. Kuwahara, J. D. Hennebold, A. B. Tavares, H. Negishi, T. H. Lee, G. F. Erickson, and E. Y. Adashi The Regulated Expression of the Pregnancy-Associated Plasma Protein-A in the Rodent Ovary: A Proposed Role in the Development of Dominant Follicles and of Corpora Lutea Endocrinology, May 1, 2002; 143(5): 1833 - 1844. [Abstract] [Full Text] [PDF]

				M. Mihm, E.J. Austin, T.E.M. Good, J.L.H. Ireland, P.G. Knight, J.F. Roche, and a. J.J. Ireland Identification of Potential Intrafollicular Factors Involved in Selection of Dominant Follicles in Heifers Biol Reprod, September 1, 2000; 63(3): 811 - 819. [Abstract] [Full Text]

				W. C.E. Nicholson, Z. Ge, D. M. Plotner, C. E. Farin, and J. E. Gadsby Insulin-Like Growth Factor (IGF)-I, IGF-I Receptor, and IGF Binding Protein-3 Messenger Ribonucleic Acids and Protein in Corpora Lutea from ProstaglandinF2{alpha}-Treated Gilts Biol Reprod, December 1, 1999; 61(6): 1527 - 1534. [Abstract] [Full Text]

				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]

				D. Chamoun, M. D. DeMoura, E. Levitas, C. E. Resnick, S. E. Gargosky, R. G. Rosenfeld, T. Matsumoto, and E. Y. Adashi Transcriptional and Posttranscriptional Regulation of Intraovarian Insulin-Like Growth Factor-Binding Proteins by Interleukin-1{beta} (IL-1{beta}): Evidence for IL-1{beta} as an Antiatretic Principal Endocrinology, August 1, 1999; 140(8): 3488 - 3495. [Abstract] [Full Text]

				S.-A. Wandji, T. L. Wood, J. Crawford, S. W. Levison, and J. M. Hammond Expression of Mouse Ovarian Insulin Growth Factor System Components During Follicular Development and Atresia Endocrinology, December 1, 1998; 139(12): 5205 - 5214. [Abstract] [Full Text] [PDF]

				E. Y. Adashi, C. E. Resnick, D. W. Payne, R. G. Rosenfeld, T. Matsumoto, M. K. Hunter, S. E. Gargosky, J. Zhou, and C. A. Bondy The Mouse Intraovarian Insulin-Like Growth Factor I System: Departures from the Rat Paradigm Endocrinology, September 1, 1997; 138(9): 3881 - 3890. [Abstract] [Full Text] [PDF]

				L. Putowski, R. M. Rohan, D. S. Choi, W. J. Scherzer, E. Ricciarelli, J. Mordacq, K. E. Mayo, and E. Y. Adashi Rat Ovarian Insulin-Like Growth Factor Binding Protein-4: A Hormone-Dependent Granulosa Cell-Derived Antigonadotropin Reproductive Sciences, May 1, 1997; 4(3): 144 - 151. [Abstract] [PDF]

				D. Choi, L. T. Putowski, P. J. Fielder, R. G. Rosenfeld, R. M. Rohan, and E. Y. Adashi Characterization and Hormonal Regulation of Granulosa Cell-Derived Insulin-Like Growth Factor Binding Protein-4 Reproductive Sciences, May 1, 1996; 3(3): 145 - 151. [Abstract] [PDF]

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

				C. A. Conover, S. K. Durham, Jür. Zapf, F. R. Masiarz, and M. C. Kiefer Cleavage Analysis of Insulin-like Growth Factor (IGF)-dependent IGF-binding Protein-4 Proteolysis and Expression of Protease-resistant IGF-binding Protein-4 Mutants J. Biol. Chem., March 3, 1995; 270(9): 4395 - 4400. [Abstract] [Full Text] [PDF]