Involvement of SOCS-1, the suppressor of cytokine signaling, in the prevention of prolactin-responsive gene expression in decidual cells

The cells forming the rat decidua produce PRL and PRL-related proteins and express both the long and short forms of the PRL receptor. Yet, only a defi ned subpopulation, the mesometrial cells, express the PRL-dependent alpha(2 )-macroglobulin gene. This gene is silenced in vivo in the antimesometrial cells and in the CC-AD cell line, derived from antimesometrial cells. To ex amine whether the lack of alpha(2)-macroglobulin expression is due to defec tive components in the PRL signaling pathway, we compared the relative expr ession of Janus kinase 2 (Jak2), signal transducer and activator of transcr iption 5 a and b (Stat5 a and b), suppressor of cytokine signaling-1 (SOCS- 1), and the tyrosine phosphatase SHP-2 mRNA in mesometrial and antimesometr ial decidua on days 12 and 13 of pseudopregnancy, the time of maximal alpha (2)-macroglobulin expression. We found no significant differences in the re lative expression of either Jak2, State (a and b), or SHP-2 in the two cell populations. However, we discovered a profound difference in the expressio n of SOCS-1, an inhibitor of the Jak/Stat pathway. This gene was highly exp ressed in the antimesometrial cells and in the GG-AD cells, which do not pr oduce alpha(2)-macroglobulin. Immunoprecipitation experiments with CC-AD ce lls revealed that although Jak2 and State coprecipitate in response to PRL stimulation, no phosphorylation of Jak2 and State could be observed. To exa mine whether SOCS-1 plays a role in silencing the alpha(2)-macroglobulin ge ne, we cultured CC-AD cells in the presence of either a SOCS-1 antisense ol igonucleotide or an irrelevant oligonucleotide for 4, 12, and 28 h. Cells w ere also treated with PRL. Within 4 h of SOCS-1 antisense treatment, alpha( 2)-macroglobulin mRNA expression was initiated. After 28 h, only cells trea ted with PRL and SOCS-1 antisense oligonucleotide retained the ability to e xpress the alpha(2)-macroglobulin gene. In summary, results of this study r eveal that constitutive expression of SOCS-1 can prevent PRL signaling and that the lack of PRL-induced expression of alpha(2)-macroglobulin in a defi ned decidual cell population is largely due to SOCS-1 expression in these c ells.