HEMATOPOIETIC STEM-CELL ANTIGEN-1 (SCA-1) EXPRESSION IN DIFFERENT LYMPHOID-TISSUES OF FEMALE MICE TREATED WITH GNRH AGONIST

PROBLEM: Our earlier studies have demonstrated a general suppression of leukocyte maturation upon GnRH agonist treatment in mice and suggested a potential effect at an early stem cell stage of leukocyte development. METHOD: Three-week old Balb/c and C57BL/6 female mice received 50 mu g injections of Lupron depot or placebo. Sequential changes in Sca-1(+) cells in the bone marrow, thymus, blood and spleen were studied by flow cytometry. RESULTS: In bone marrow, the absolute numbers of Sca-1(+) cells were significantly decreased at 2 weeks in C57BL/6 mice whereas a decreasing trend was noted in Balb/c mice following agonist administration. Concomitantly, thymocytes expressing Sca-1(+) cells were significantly increased at 2 weeks in C57BL/6 mice: but were significantly decreased in Balb/c mice. Significant decreases in Sca-1(+) cells were also observed in spleen and blood in Balb/c mice whereas no significant differences were observed in C57BL/6 mice. CONCLUSIONS: These data suggest GnRH agonists affect hematopoietic stem cell development in mice, The effects observed vary with different genetic backgrounds. In Balb/c mice these effects are more pronounced, and appear to result in the inhibition of stem cell maturation. In contrast, GnRH agonist enhances stem cell maturation in C57BL/6 mice.