This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted 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 Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hourvitz, A. Articles by Erickson, G. F. Search for Related Content PubMed PubMed Citation Articles by Hourvitz, A. Articles by Erickson, G. F.

Pregnancy-Associated Plasma Protein-A Gene Expression in Human Ovaries Is Restricted to Healthy Follicles and Corpora Lutea

Division of Reproductive Sciences, Department of Obstetrics and Gynecology (A.H., E.Y.A.), University of Utah Health Science Center, Salt Lake City, Utah; and Department of Reproductive Medicine (A.E.W., F.L.T.F., R.J.C., G.F.E.), University of California San Diego, La Jolla California 92093-0674

Abstract

Recently, Pregnancy-Associated Plasma Protein-A (PAPP-A) in human follicular fluid was identified as an insulin-like growth factor binding protein-4 protease (IGFBP-4ase). The ability of IGFBP-4ase to inactivate the FSH antagonist, IGFBP-4, has suggested a possible role for PAPP-A in regulating FSH action. Despite growing interest in this protease, the question of whether the PAPP-A gene is expressed in ovaries of normal cycling women is unknown. To fill this basic gap in our knowledge, we have identified the cellular sites of PAPP-A gene expression in normal human ovaries by in situ hybridization. PAPP-A mRNA was low or undetectable in preantral follicles, small (1–2 mm) healthy and atretic antral follicles, larger atretic antral follicles, surface epithelium, tunica albuginea and connective tissue cells. In contrast, an intense PAPP-A hybridization signal was evident in the healthy antral follicles examined from 5 mm to the preovulatory stage. In these follicles, the signal was restricted to the granulosa cells (GC). An intense signal for PAPP-A mRNA was also present in healthy corpora lutea (CL), being localized to a subset of large luteal cells. Collectively, these results provide the first evidence that the gene encoding PAPP-A is expressed in ovaries of normal cycling women and show that the gene is expressed almost exclusively in healthy GC and CL cells. The restricted pattern of PAPP-A expression in normal human ovaries suggests that PAPP-A may be a functional marker of the dominant follicle and its product, the CL. Although the physiological function of ovarian PAPP-A remains to be identified, we hypothesize it might play a role in controlling survival, growth, and/or differentiation of the dominant follicle and CL by inactivating the gonadotropin antagonist, IGFBP-4.

This article has been cited by other articles:

				S. Assou, T. Anahory, V. Pantesco, T. Le Carrour, F. Pellestor, B. Klein, L. Reyftmann, H. Dechaud, J. De Vos, and S. Hamamah The human cumulus-oocyte complex gene-expression profile Hum. Reprod., July 1, 2006; 21(7): 1705 - 1719. [Abstract] [Full Text] [PDF]

				Q.-P. Qin, S. Kokkala, J. Lund, N. Tamm, L.-M. Voipio-Pulkki, and K. Pettersson Molecular Distinction of Circulating Pregnancy-Associated Plasma Protein A in Myocardial Infarction and Pregnancy Clin. Chem., January 1, 2005; 51(1): 75 - 83. [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]

				L. J. Spicer Proteolytic Degradation of Insulin-Like Growth Factor Binding Proteins by Ovarian Follicles: A Control Mechanism for Selection of Dominant Follicles Biol Reprod, May 1, 2004; 70(5): 1223 - 1230. [Abstract] [Full Text] [PDF]

				B.-K. Chen, K. M. Leiferman, M. R. Pittelkow, M. T. Overgaard, C. Oxvig, and C. A. Conover Localization and Regulation of Pregnancy-Associated Plasma Protein A Expression in Healing Human Skin J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4465 - 4471. [Abstract] [Full Text] [PDF]

				J. Zhou, J. Wang, D. Penny, P. Monget, J. A. Arraztoa, L. J. Fogelson, and C. A. Bondy Insulin-Like Growth Factor Binding Protein 4 Expression Parallels Luteinizing Hormone Receptor Expression and Follicular Luteinization in the Primate Ovary Biol Reprod, July 1, 2003; 69(1): 22 - 29. [Abstract] [Full Text] [PDF]

				G. M. Rivera and J. E. Fortune Selection of the Dominant Follicle and Insulin-Like Growth Factor (IGF)-Binding Proteins: Evidence that Pregnancy-Associated Plasma Protein A Contributes to Proteolysis of IGF-Binding Protein 5 in Bovine Follicular Fluid Endocrinology, February 1, 2003; 144(2): 437 - 446. [Abstract] [Full Text] [PDF]

				P. Monget, S. Mazerbourg, T. Delpuech, M.-C. Maurel, S. Maniere, J. Zapf, G. Lalmanach, C. Oxvig, and M. T. Overgaard Pregnancy-Associated Plasma Protein-A Is Involved in Insulin-Like Growth Factor Binding Protein-2 (IGFBP-2) Proteolytic Degradation in Bovine and Porcine Preovulatory Follicles: Identification of Cleavage Site and Characterization of IGFBP-2 Degradation Biol Reprod, January 1, 2003; 68(1): 77 - 86. [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]

				F. L. Teixeira Filho, E. C. Baracat, T. H. Lee, C. S. Suh, M. Matsui, R. J. Chang, S. Shimasaki, and G. F. Erickson Aberrant Expression of Growth Differentiation Factor-9 in Oocytes of Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1337 - 1344. [Abstract] [Full Text] [PDF]

				S. Mazerbourg, M. T. Overgaard, C. Oxvig, M. Christiansen, C. A. Conover, I. Laurendeau, M. Vidaud, G. Tosser-Klopp, J. Zapf, and P. Monget Pregnancy-Associated Plasma Protein-A (PAPP-A) in Ovine, Bovine, Porcine, and Equine Ovarian Follicles: Involvement in IGF Binding Protein-4 Proteolytic Degradation and mRNA Expression During Follicular Development Endocrinology, December 1, 2001; 142(12): 5243 - 5253. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted 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 Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hourvitz, A. Articles by Erickson, G. F. Search for Related Content PubMed PubMed Citation Articles by Hourvitz, A. Articles by Erickson, G. F.