Endocrinology, Vol 125, 2985-2995, Copyright © 1989 by Endocrine Society

ARTICLES

Hormonal regulation and tissue-specific localization of alpha 2- macroglobulin in rat ovarian follicles and corpora lutea

D Gaddy-Kurten, GJ Hickey, GH Fey, J Gauldie and JS Richards
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.

alpha 2-Macroglobulin (alpha 2M) is a broad spectrum protease inhibitor associated with inflammatory responses and proposed to be important in tissue remodeling. alpha 2 M also functions as a carrier of specific growth factors and cytokines, including platelet-derived growth factor, transforming growth factor-beta, basic fibroblast growth factor, interleukin-1, interleukin-6. To determine whether alpha 2M is associated with remodeling phenomena in the rat ovary, the expression of alpha 2M mRNA and protein has been analyzed in specific ovarian cell types during ovulation, luteinization, and luteolysis. Before ovulation, alpha 2M mRNA is not detectable in granulosa cells. Twelve hours after injection of an ovulatory dose of hCG a 5.2-kilobase alpha 2M mRNA is detectable in luteinizing follicles, which is increased further by 48 h and maintained in corpora lutea (CL) for up to 96 h. Administration of PRL from 24-96 h results in both inhibition of luteolysis and marked increases in alpha 2M mRNA in CL, but not in residual tissues, of these same ovaries, isolated 48, 72, and 96 h after an ovulatory dose of hCG, alpha 2M mRNA is also induced by PRL in cultures of luteinized granulosa cells. These changes in alpha 2M mRNA in follicles or developing CL do not appear to reflect the amount of alpha 2M protein present: alpha 2M protein (188K monomer) is present (immunoblot and immunofluorescence data) in small antral and preovulatory follicles even though mRNA is not detectable; after an ovulatory dose of hCG the protein level transiently increases by 12 h (approximately 5-fold) and declines thereafter through 96 h; the decrease in alpha 2M protein observed at 48-96 h is delayed but not abolished by treatment with PRL, even though the mRNA levels continue to rise during this same time period. In contrast, changes in alpha 2M mRNA and protein are regulated coordinately in CL of pregnant rats. alpha 2M mRNA is present, but in low concentration, from days 4-11 of gestation, increases markedly between days 11-21, and decreases at parturition, when functional luteolysis occurs. Hysterectomy of day 10 pregnant rats combined with hormone replacement determined that alpha 2M mRNA levels are regulated primarily by PRL through day 12 and by placental lactogens during midgestation (days 12-15). The increase in alpha 2M mRNA during pregnancy precedes the 40-fold increase (peak) in a alpha 2M protein observed on day 15, which remains elevated through day 21.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				S. R. Soares, R. Gomez, C. Simon, J. A. Garcia-Velasco, and A. Pellicer Targeting the vascular endothelial growth factor system to prevent ovarian hyperstimulation syndrome Hum. Reprod. Update, April 2, 2008; (2008) dmn008v1. [Abstract] [Full Text] [PDF]

				S. Gao, C. De Geyter, K. Kossowska, and H. Zhang FSH stimulates the expression of the ADAMTS-16 protease in mature human ovarian follicles Mol. Hum. Reprod., July 1, 2007; 13(7): 465 - 471. [Abstract] [Full Text] [PDF]

				E. Pau, I. Alonso-Muriel, R. Gomez, E. Novella, A. Ruiz, J. A. Garcia-Velasco, C. Simon, and A. Pellicer Plasma levels of soluble vascular endothelial growth factor receptor-1 may determine the onset of early and late ovarian hyperstimulation syndrome Hum. Reprod., June 1, 2006; 21(6): 1453 - 1460. [Abstract] [Full Text] [PDF]

				W.-Y. Lui, Y. H. Cheng, D. D Mruk, C. H. Cheng, M. Y. Mo, W. M Lee, and C Y. Cheng {alpha}2-Macroglobulin expression in the liver in response to inflammation is mediated by the testis J. Endocrinol., June 1, 2005; 185(3): 497 - 505. [Abstract] [Full Text] [PDF]

				H. He, D. J. McCartney, Q. Wei, S. Esadeg, J. Zhang, R. A. Foster, M. A. Hayes, C. Tayade, F. Van Leuven, and B. A. Croy Characterization of a Murine Alpha 2 Macroglobulin Gene Expressed in Reproductive and Cardiovascular Tissue Biol Reprod, February 1, 2005; 72(2): 266 - 275. [Abstract] [Full Text] [PDF]

				M F Smith, C G Gutierrez, W A Ricke, D G Armstrong, and R Webb Production of matrix metalloproteinases by cultured bovine theca and granulosa cells Reproduction, January 1, 2005; 129(1): 75 - 87. [Abstract] [Full Text] [PDF]

				M. Jo, M. C. Gieske, C. E. Payne, S. E. Wheeler-Price, J. B. Gieske, I. V. Ignatius, T. E. Curry Jr., and C. Ko Development and Application of a Rat Ovarian Gene Expression Database Endocrinology, November 1, 2004; 145(11): 5384 - 5396. [Abstract] [Full Text] [PDF]

				J. L. H. Ireland, F. Jimenez-Krassel, M. E. Winn, D. S. Burns, and J. J. Ireland Evidence for Autocrine or Paracrine Roles of {alpha}2-Macroglobulin in Regulation of Estradiol Production by Granulosa Cells and Development of Dominant Follicles Endocrinology, June 1, 2004; 145(6): 2784 - 2794. [Abstract] [Full Text] [PDF]

				T. E. Curry Jr. and K. G. Osteen The Matrix Metalloproteinase System: Changes, Regulation, and Impact throughout the Ovarian and Uterine Reproductive Cycle Endocr. Rev., August 1, 2003; 24(4): 428 - 465. [Abstract] [Full Text] [PDF]

				B. McElhinney, J. Ardill, C. Caldwell, F. Lloyd, and N. McClure Ovarian hyperstimulation syndrome and assisted reproductive technologies: why some and not others? Hum. Reprod., June 1, 2002; 17(6): 1548 - 1553. [Abstract] [Full Text] [PDF]

				P. E. Saragueta, G. M. Lanuza, and J. L. Baranao Autocrine Role of Transforming Growth Factor {beta}1 on Rat Granulosa Cell Proliferation Biol Reprod, June 1, 2002; 66(6): 1862 - 1868. [Abstract] [Full Text] [PDF]

				T. E. Curry Jr., L. Song, and S. E. Wheeler Cellular Localization of Gelatinases and Tissue Inhibitors of Metalloproteinases During Follicular Growth, Ovulation, and Early Luteal Formation in the Rat Biol Reprod, September 1, 2001; 65(3): 855 - 865. [Abstract] [Full Text] [PDF]

				T. E. Curry Jr and K. G. Osteen Cyclic Changes in the Matrix Metalloproteinase System in the Ovary and Uterus Biol Reprod, May 1, 2001; 64(5): 1285 - 1296. [Abstract] [Full Text]

				T. N. Alliston, I. J. Gonzalez-Robayna, P. Buse, G. L. Firestone, and J. S. Richards Expression and Localization of Serum/Glucocorticoid-Induced Kinase in the Rat Ovary: Relation to Follicular Growth and Differentiation Endocrinology, January 1, 2000; 141(1): 385 - 395. [Abstract] [Full Text] [PDF]

				D. L. Russell and J. S. Richards Differentiation-Dependent Prolactin Responsiveness and Stat (Signal Transducers and Activators of Transcription) Signaling in Rat Ovarian Cells Mol. Endocrinol., December 1, 1999; 13(12): 2049 - 2064. [Abstract] [Full Text]

				R. G. I. Cooke, W. B. Nothnick, C. Komar, P. Burns, and T. E. Curry Jr Collagenase and Gelatinase Messenger Ribonucleic Acid Expression and Activity During Follicular Development in the Rat Ovary Biol Reprod, November 1, 1999; 61(5): 1309 - 1316. [Abstract] [Full Text]

				M. Dajee, G. H. Fey, and J. S. Richards Stat 5b and the Orphan Nuclear Receptors Regulate Expression of the {alpha}2-Macroglobulin ({alpha}2M) Gene in Rat Ovarian Granulosa Cells Mol. Endocrinol., September 1, 1998; 12(9): 1393 - 1409. [Abstract] [Full Text]

				L. Braghiroli, B. Silvestrini, C. Sorrentino, J. Grima, D. Mruk, and C. Yan Cheng Regulation of {alpha}2-Macroglobulin Expression in Rat Sertoli Cells and Hepatocytes by Germ Cells In Vitro Biol Reprod, July 1, 1998; 59(1): 111 - 123. [Abstract] [Full Text]

				W. R. Duan, D. I.H. Linzer, and G. Gibori Cloning and Characterization of an Ovarian-specific Protein That Associates with the Short Form of the Prolactin Receptor J. Biol. Chem., June 28, 1996; 271(26): 15602 - 15607. [Abstract] [Full Text] [PDF]