The role of estrogen receptors and androgen receptors in sex steroid regulation of B lymphopoiesis.
The role of estrogen receptors and androgen receptors in sex steroid regulation of B lymphopoiesis.
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DOI：
10.4049/jimmunol.161.1.27
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发表时间：
1998-07
影响因子：
4.4
通讯作者：
G. Smithson;J. F. Couse;D. Lubahn;K. Korach;P. Kincade
中科院分区：
文献类型：
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作者：
G. Smithson;J. F. Couse;D. Lubahn;K. Korach;P. Kincade
一些观察结果表明性类固醇可能参与 B 淋巴细胞生成的稳态调节。怀孕或雌激素治疗小鼠的骨髓中 B 细胞前体急剧下降。相反，在性腺功能减退小鼠或雄性去势小鼠中，相同的细胞群也会增加。性腺功能减退小鼠的雌激素治疗使前体细胞恢复正常。然而，关于哪些激素和受体最重要的问题仍然存在。此外，这些观察结果需要与新性类固醇受体的进展相协调。我们现在已经对雄激素受体缺陷型睾丸女性化 (Tfm) 小鼠的 B 淋巴细胞生成进行了表征。与野生型小鼠相比，睾丸女性化小鼠的骨髓中 B 细胞前体数量和脾脏中 B 细胞数量显着增加。在基因靶向小鼠中评估了一种雌激素受体（ERα）的重要性，发现 B 细胞前体处于正常范围内。我们之前的研究表明，基质细胞中的激素受体可能对雌激素介导的 B 淋巴细胞生成抑制很重要。我们现在表明，特定雌激素受体拮抗剂 (ICI 182,780) 可以阻断培养物中雌激素介导的 B 细胞前体扩增抑制。来自 ER α 靶向骨髓的基质细胞具有完全雌激素反应性。对这些基质细胞的 RT-PCR 分析揭示了 ER α 的剪接变异转录本，以及最近发现的雌激素结合受体 ER β 的信息。因此，雄激素通常可以通过雄激素受体抑制B淋巴细胞生成，而雌激素可能利用一种或多种受体来实现相同的生理反应。
Several observations suggest that sex steroids might participate in steady state regulation of B lymphopoiesis. B cell precursors decline dramatically in bone marrow of pregnant or estrogen-treated mice. Reciprocally, the same cell populations are increased in hypogonadal mice or male castrates. Estrogen treatment of hypogonadal mice reduced precursors to normal. However, questions remain about which hormones and receptors are the most important. Furthermore, these observations need to be reconciled with advances regarding new sex steroid receptors. We have now characterized B lymphopoiesis in androgen receptor-deficient testicular feminization (Tfm) mice. Testicular feminization mice had substantially elevated numbers of B cell precursors in the bone marrow and B cells in the spleen as compared with wild-type mice. The importance of one estrogen receptor (ER alpha) was evaluated in gene-targeted mice, and B cell precursors were found to be within the normal range. Our previous studies indicated that hormone receptors in stromal cells may be important for estrogen-mediated suppression of B lymphopoiesis. We now show that estrogen-mediated inhibition of B cell precursor expansion in culture was blocked by a specific estrogen receptor antagonist (ICI 182,780). Stromal cells derived from ER alpha-targeted bone marrow were fully estrogen responsive. RT-PCR analyses of these stromal cells revealed splice-variant transcripts of ER alpha, as well as message for a recently discovered estrogen-binding receptor, ER beta. Thus, androgens may normally inhibit B lymphopoiesis through the androgen receptor, whereas estrogens might utilize one or more receptors to achieve the same physiologic response.