Evidence for autocrine or paracrine roles of alpha2-macroglobulin in regulation of estradiol production by granulosa cells and development of dominant follicles.
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.
Molecular Reproductive Endocrinology Laboratory, Department of Animal Science, Michigan State University, East Lansing, Michigan 48824-1225, USA. ireland@msu.edu
J L H
JL
Ireland
F
F
Jimenez-Krassel
M E
ME
Winn
D S
DS
Burns
J J
JJ
Ireland
D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D004958:Estradiol / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000302:isolation & purification; D006080:Ovarian Follicle / Q000378:metabolism / Q000502:physiology*; D010060:Ovulation; D019899:Paracrine Communication / Q000502:physiology*; D000511:alpha-Macroglobulins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D000511:alpha-Macroglobulins; D004958:Estradiol