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.
Ireland
J L H
JL
Molecular Reproductive Endocrinology Laboratory, Department of Animal Science, Michigan State University, East Lansing, Michigan 48824-1225, USA. ireland@msu.edu
Jimenez-Krassel
F
F
Winn
M E
ME
Burns
D S
DS
Ireland
J J
JJ
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