REGULATION OF ALPHA-2-MACROGLOBULIN BY LUTEINIZING-HORMONE AND PROLACTIN DURING CELL-DIFFERENTIATION IN THE RAT OVARY

Alph-alpha-2-macroglobulin (alpha-2M), a protease inhibitor which also binds growth factors and cytokines, is temporally expressed in association with remodelling phenomena in the ovary: ovulation and luteinization. Specific hormonal, cellular, subcellular, and molecular events regulating alpha-2M mRNA and protein have been analyzed during follicular growth, ovulation, and luteinization using complementary in vivo and in vitro models. Data demonstrate that alpha-2M mRNA and protein are synthesized in thecal cells of developing follicles in response to low levels of LH. Conversely, alpha-2M mRNA and protein are only synthesized by granulosa cells of follicles that have been stimulated to luteinize either in vivo by the LH surge or in vitro by FSH and testosterone and are also exposed to PRL. The obligatory requirement for PRL is specific; associated with increased numbers of PRL-binding sites; mediated by time-dependent appearance of alpha-2M in the endoplasmic reticulum (12 h), Golgi apparatus (24 h), and secretion vesicles (48 h); and involves in part increased transcription of the alpha-2M gene.