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Endocrinology Vol. 145, No. 6 2784-2794
Copyright © 2004 by The Endocrine Society

Evidence for Autocrine or Paracrine Roles of {alpha}2-Macroglobulin in Regulation of Estradiol Production by Granulosa Cells and Development of Dominant Follicles

J. L. H. Ireland, F. Jimenez-Krassel, M. E. Winn, D. S. Burns and J. J. Ireland

Molecular Reproductive Endocrinology Laboratory, Department of Animal Science, Michigan State University, East Lansing, Michigan 48824-1225

Address all correspondence and requests for reprints to: J. J. Ireland, Molecular Reproductive Endocrinology Laboratory, Department of Animal Science, Michigan State University, East Lansing, Michigan 48824-1225. E-mail: ireland{at}msu.edu.

{alpha}2-Macroglobulin ({alpha}2-M) inhibits proteinases and modulates the actions of growth factors and cytokines. Despite the key roles proteinases, growth factors, and cytokines have in folliculogenesis, the role of {alpha}2-M in follicular development is unknown. Our objectives were to: 1) determine whether granulosa cells produce {alpha}2-M and have {alpha}2-M receptors, 2) examine the effect of {alpha}2-M on estradiol production by granulosa cells, 3) establish whether amounts of {alpha}2-M and {alpha}2-M receptors were altered during dominant nonovulatory follicle development, and 4) examine {alpha}2-M’s mechanism of action. The results demonstrated that bovine granulosa cells contain 5.2- and 15-kb mRNAs and 720- and 500-kDa proteins that correspond, respectively, to sizes of mRNAs and proteins for {alpha}2-M and the {alpha}2-M receptor. Treatment of granulosa cells with {alpha}2-M resulted in a specific dose-responsive increase in estradiol production. Cell viability, cell number, and the amount of aromatase in granulosa cells were not altered by {alpha}2-M. Treatment of granulosa cells with factors that bind {alpha}2-M or its receptor did not mimic {alpha}2-M action. Although intrafollicular amounts of {alpha}2-M remained unchanged, amounts of {alpha}2-M receptor in granulosa cells were strongly inversely associated with concentrations of estradiol in dominant and subordinate follicles. Based on these results, we concluded that {alpha}2-M may have autocrine or paracrine roles in granulosa cells potentially important for regulation of estradiol production and development of dominant follicles.




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