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This version published online on March 4, 2004
Endocrinology, doi:10.1210/en.2003-1407
A more recent version of this article appeared on June 1, 2004
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Submitted on October 20, 2003
Accepted on February 23, 2004

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, MI 48824-1225

* To whom correspondence should be addressed. 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: a) determine if granulosa cells produce {alpha}2-M and have {alpha}2-M receptors, b) examine the effect of {alpha}2-M on estradiol production by granulosa cells, c) establish whether amounts of {alpha}2-M and {alpha}2-M receptors were altered during dominant non-ovulatory follicle development, and d) examine {alpha}2-M's mechanism of action. The results demonstrated that bovine granulosa cells contain 5.2 Kb and 15 Kb mRNAs, and 720 kDa 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.
Key words: {alpha}2-macroglobulin • estradiol • granulosa cells




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