Expression and function of proenkephalin A messenger ribonucleic acid in murine fetal thymocytes

In recent years we examined the function of the endogenous enkephalins encoded by PEA messenger RNA (mRNA) expressed in murine thymocytes, the precursor cells to T lymphocytes, which are the primary effector cells in cell- mediated immune responses. In the present study, we examined the expression and function of PEA mRNA and enkephalins in fetal thymocytes. By Northern gel and in situ hybridization techniques, we show that PEA mRNA is constitutively expressed in fetal thymocytes early in gestation, with maximal expression occurring on day 15. By birth, PEA mRNA is no longer constitutively expressed, but can be induced by culturing newborn thymocytes with the T cell-specific mitogen, Concanavalin-A. Both a delta-opioid receptor antagonist, naltrindole, and a PEA mRNA-specific antisense complementary DNA enhance the spontaneous proliferation of day 15, but not day 14, fetal thymocytes, consistent with the observation that PEA mRNA is expressed in thymocytes on day 15, but not day 14, of gestation. The enhanced proliferation of day 15 fetal thymocytes is reversed by a delta-opioid receptor agonist, deltorphin. The data suggest that endogenous enkephalins encoded by PEA mRNA expressed in day 15 fetal thymocytes act to inhibit the spontaneous proliferation of these cells, perhaps so that their differentiation into mature T lymphocytes can occur.