Rao L V, Cleveland R P, Kimmel R J, Ataya K M
Department of Obstetrics and Gynecology, Case Western Reserve University, Cleveland, OH, USA.
Am J Reprod Immunol. 1995 Oct;34(4):257-66. doi: 10.1111/j.1600-0897.1995.tb00950.x.
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.
Three-week old Balb/c and C57BL/6 female mice received 50 micrograms 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.
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.
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.
我们早期的研究已经证明,在小鼠中使用促性腺激素释放激素(GnRH)激动剂治疗后,白细胞成熟受到普遍抑制,并提示在白细胞发育的早期干细胞阶段可能存在潜在影响。
3周龄的Balb/c和C57BL/6雌性小鼠接受50微克的亮丙瑞林长效注射剂或安慰剂注射。通过流式细胞术研究骨髓、胸腺、血液和脾脏中Sca-1+细胞的连续变化。
在骨髓中,C57BL/6小鼠在给药2周时Sca-1+细胞的绝对数量显著减少,而Balb/c小鼠在给予激动剂后呈现下降趋势。同时,C57BL/6小鼠在2周时表达Sca-1+细胞的胸腺细胞显著增加,但Balb/c小鼠中的此类细胞显著减少。在Balb/c小鼠的脾脏和血液中也观察到Sca-1+细胞显著减少,而C57BL/6小鼠中未观察到显著差异。
这些数据表明GnRH激动剂会影响小鼠造血干细胞的发育。观察到的效应因不同的遗传背景而异。在Balb/c小鼠中,这些效应更为明显,似乎导致干细胞成熟受到抑制。相比之下,GnRH激动剂会增强C57BL/6小鼠的干细胞成熟。