Hormonal Regulation and Tissue-Specific Localization of α2-Macroglobulin in Rat Ovarian Follicles and Corpora Lutea*
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abstract
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)
