Impairing follicle-stimulating hormone (FSH) signaling in vivo:: Targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance
Impairing follicle-stimulating hormone (FSH) signaling in vivo:: Targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance
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DOI：
10.1073/pnas.95.23.13612
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发表时间：
1998-11-10
影响因子：
11.1
通讯作者：
Sassone-Corsi, P
中科院分区：
文献类型：
--
作者：
Dierich, A;Sairam, MR;Sassone-Corsi, P
促性腺激素、卵泡刺激素(FSH)和黄体生成素通过调节生殖细胞的增殖和分化来刺激性腺。卵泡刺激素受体(FSH-Rs)定位于睾丸支持细胞和卵巢颗粒细胞，与腺苷环化酶激活等信号转导途径相偶联。FSH-Rs的激活被认为是女性卵泡发生和男性精子发生所必需的。我们通过同源重组产生了缺乏FSH-R的小鼠，FSH-R缺乏的雄性小鼠具有生育能力，但表现为较小的睾丸和部分生精失败。因此，尽管FSH信号不是启动精子发生所必需的，但它似乎是精子足够的存活率和活力所必需的。FSH-R缺乏的女性表现为子宫较薄，卵巢较小，并且由于卵泡形成之前卵泡发育受阻而不育。虽然标记基因的表达在FSH-R-/-小鼠中只有轻微的变化，但在各种激素的狂欢中观察到了性别特异性的剧烈变化。女性的脑下垂体前叶增大，并显示大量FSH和促甲状腺激素(TSH)阳性细胞。FSH-R-/-小鼠的表型使人联想到人类高促性腺激素卵巢发育不全和不孕症。
Pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone stimulate the gonads by regulating germ cell proliferation and differentiation. FSH receptors (FSH-Rs) are localized to testicular Sertoli cells and ovarian granulosa cells and are coupled to activation of the adenylyl cyclase and other signaling pathways. Activation of FSH-Rs is considered essential for folliculogenesis in the female and spermatogenesis in the male. We have generated mice lacking FSH-R by homologous recombination, FSH-R-deficient males are fertile but display small testes and partial spermatogenic failure. Thus, although FSH signaling is not essential for initiating spermatogenesis, it appears to be required for adequate viability and motility of the sperms. FSH-R-deficient females display thin uteri and small ovaries and are sterile because of a block in folliculogenesis before antral follicle formation. Although the expression of marker genes is only moderately altered in FSH-R -/- mice, drastic sex-specific changes are observed in the revels of various hormones. The anterior lobe of the pituitary gland in females is enlarged and reveals a larger number of FSH- and thyroid-stimulating hormone (TSH)-positive cells. The phenotype of FSH-R -/- mice is reminiscent of human hypergonadotropic ovarian dysgenesis and infertility.