Crandall T L, Joyce R A, Boggs D R
J Lab Clin Med. 1980 Jun;95(6):857-67.
The effect of ES upon hematopoiesis was studied following 4 to 24 weeks of administration in adult female mice. ES produced osteosclerosis, hepatomegaly, splenomegaly with an increase in splenic erythropoiesis mild anemai, and a relatively stable, moderately severe neutropenia. Intact and splenectomized mice failed to develop hepatic hematopoiesis to compensate for these blood changes. The neutropenia was characterized by a proportionally normal-sized marginal granulocyte pool and a reduced marrow granulocyte reserve in the marrow, cellularity, peroxidase-positive cells. CFU-S, and CFU-GM declined during 4 to 12 weeks of study in the same study period, splenic granulocytopoiesis increased as measured by these perameters, but it only partially compensated for the neutropenia. CSA was present in serum, and no inhibitors of in vitro granulocytopoiesis were detected. The direct addition of E3S to normal murine marrow cells in vitro failed to inhibit CFU=GM proliferation. Daily ES administration failed to inhibit in vivo granulocytopoiesis in diffusion chambers. These studies suggest that ES-induced neutropenia is not due to direct inhibition of CFU-S or CFU-GM proliferation or differentiation to mature granulocytes and by implication, suggest that it may be mediated through effects on the hematopoietic microenvironment.
在成年雌性小鼠中连续给药4至24周后，研究了雌激素（ES）对造血的影响。ES导致骨硬化、肝肿大、脾肿大，伴有脾红细胞生成增加、轻度贫血以及相对稳定的中度严重中性粒细胞减少。完整小鼠和脾切除小鼠均未出现肝造血以代偿这些血液变化。中性粒细胞减少的特征是边缘粒细胞池大小比例正常，而骨髓中的骨髓粒细胞储备减少，包括细胞数量、过氧化物酶阳性细胞。在研究的4至12周期间，脾集落形成单位（CFU-S）和粒细胞-巨噬细胞集落形成单位（CFU-GM）数量下降，同时，通过这些参数测量发现脾粒细胞生成增加，但仅部分代偿了中性粒细胞减少。血清中存在集落刺激活性（CSA），未检测到体外粒细胞生成的抑制剂。体外将ES直接添加到正常小鼠骨髓细胞中未能抑制CFU-GM增殖。每日给予ES未能抑制扩散盒内的体内粒细胞生成。这些研究表明，ES诱导的中性粒细胞减少不是由于直接抑制CFU-S或CFU-GM增殖或向成熟粒细胞的分化，因此暗示其可能是通过对造血微环境的影响介导的。
