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

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Abstract

OBJECTIVE

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

METHODS

Whole ovarian RNA, obtained from two models of follicular development, was extracted and analyzed by Northern blotting. Immature rats were treated with pregnant mare serum gonadotropin (PMSC) followed 48 hours later with hCG, or alternatively were hypophyseciomized and treated with FSH and/or diethylstilbestrol (DES). Localization ojTGFBP-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 transcripis 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 preantral (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 IGFBP-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, (J Soc Gynecol Invest 1997;4:144–151) Copyright © 1991 by the Society for Gynecologic Investigation.

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Authors and Affiliations

  1. Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Maryland School of Medicine, Baltimore, Maryland, USA

    Lechoslaw Putowski MD, PhD, Richard M. Rohan PhD, Doo Seok Choi MD, Wendy J. Scherzer MD, Elisabetta Ricciarelli MD, John Mordacq PhD, Kelly E. Mayo PhD & Eli Y. Adashi MD

  2. Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois, USA

    Lechoslaw Putowski MD, PhD, Richard M. Rohan PhD, Doo Seok Choi MD, Wendy J. Scherzer MD, Elisabetta Ricciarelli MD, John Mordacq PhD, Kelly E. Mayo PhD & Eli Y. Adashi MD

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  1. Lechoslaw Putowski MD, PhD
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  2. Richard M. Rohan PhD
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  3. Doo Seok Choi MD
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  4. Wendy J. Scherzer MD
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  5. Elisabetta Ricciarelli MD
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Additional information

Supported in part by National Institutes of Health (NIH) research grants HD-19998 and HD-30288 (EYA), NIH research grants HD-27491 and P30 HD-28048 (KEM). a Fulbright Fellowship (LP), an American Fertility Society/Ortho Distinguished Fellowship in Reproductive Endocrinology (WJS), a Lalor Foundation Fellowship (ER), and an award from the Frank C. Bressler Research Fund (RMR). The authors wish to thank Ms. Cornelia T. Szmajda for her invaluable assistance m the preparation of this manuscript and Keith Bailey for preparation of plasmid DNAs.

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Putowski, L., Rohan, R.M., Choi, D.S. et al. Rat Ovarian Insulin-Like Growth Factor Binding Protein-4: A Hormone-Dependent Granulosa Cell-Derived Antigonadotropin. Reprod. Sci. 4, 144–151 (1997). https://doi.org/10.1177/107155769700400306

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