This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Putowski, L. Articles by Adashi, E. Y. Search for Related Content PubMed PubMed Citation Articles by Putowski, L. Articles by Rohan, R. M. Articles by Choi, D. S. Articles by Scherzer, W. J. Articles by Ricciarelli, E. Articles by Mordacq, J. Articles by Mayo, K. E. Articles by Adashi, E. Y. Social Bookmarking                         What's this?

Rat Ovarian Insulin-Like Growth Factor Binding Protein-4: A Hormone-Dependent Granulosa Cell-Derived Antigonadotropin

Richard M. Rohan, PhD

Doo Seok Choi, MD

Wendy J. Scherzer, MD

Elisabetta Ricciarelli, MD

John Mordacq, PhD

Kelly E. Mayo, PhD

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Maryland School of Medicine, Baltimore, Maryland; Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois

Eli Y. Adashi, MD

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Maryland School of Medicine, Baltimore, Maryland; Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois; Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Utah, Health Sciences Center, 546 Chipeta Way, Suite 1100—Room #109, Salt Lake City, UT 84108

Objective: To assess the in vivo regulation of ovarian insulin-like growth factor binding protein-4 (GFBP-4) mRNA expression by gonadotropins and estrogen.

Methods: Whole varian RNA, obtained from two models of follicular development, was extracted and analyzed by Northern blotting. Immature rats were treated with pregnant mare senum gonadotropin (PMSG) followed 48 hours later with hCG, or alternatively were hypophysectomized and treated with FSH and/or diethylstilbestrol (DES). Localization of IGFBP-4 expression was assessed in the former study by in situ hybridization. Finally, the ability of human IGFBP-4 to antagonize FSH-stimulated progesterone accumulation was assessed in vitro.

Results: The ovarian content of IGFBP-4 transcripts increased threefold (P < .05) at 12 hours after PMSG but was near baseline at 24 and 48 hours. The abundance of IGFBP-4 mRNA increased (P < .05) again at 6 and 24 hours after hCG. The expression of IGFBP-4 was localized to granulosa cells of prenatral (untreated) and small antral (12 hours after PMSG) follicles. No IGFBP-4 expression was noted in large (gonadotropin-primed) antral follicles. Hypophysectomy increased (P < .05) the ovarian content of IGBP-4 mRNA by 1.5-fold, an effect further enhanced (1.8-fold; P < .05) by the provision of FSH and DES. In vitro studies revealed the ability of increasing concentrations (0.01-1 µg/mL) of recombinant human IGFBP-4 to inhibit the FSH-supported accumulation of progesterone.

Conclusion: Increased expression after administration of PMSG, hCG, and FSH/DES suggests that IGFBP-4 is a dynamic and hormonally responsive component of the ovarian cycle. The lack of expression in preovulatory follicles and its antigonadotropic actions in vitro imply that the attenuated expression of IGFBP-4 may constitute a requirement for successful follicular maturation.

Key Words: Insulin-like growth factor binding protein-4 • Carrier proteins • gonadotropins • ovary

Journal of the Society for Gynecologic Investigation, Vol. 4, No. 3, 144-151 (1997)
DOI: 10.1177/107155769700400306


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?