The effect of a null mutation in the follicle-stimulating hormone receptor gene on mouse reproduction
The effect of a null mutation in the follicle-stimulating hormone receptor gene on mouse reproduction
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DOI：
10.1210/en.141.5.1795
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发表时间：
2000-05-01
期刊：
影响因子：
4.8
通讯作者：
Charlton, HM
中科院分区：
文献类型：
--
作者：
Abel, MH;Wootton, AN;Charlton, HM
为了进一步研究脑-垂体-性腺的相互关系，我们产生了编码FSH受体的基因被破坏的小鼠。雌性FSH受体敲除（FSHRKO）小鼠不育。卵巢明显缩小，卵泡发育在前腔期停止，但有基质肥大的证据。阴道闭锁，子宫萎缩。经PMSG治疗后无反应。血清和生殖腺均未检出抑制素A和抑制素B。与对照组相比，突变雌性小鼠血清FSH和LH浓度显著升高。垂体FSH含量显著升高，LH含量不显著升高。在FSHRKO雌性小鼠中施用雌激素抑制血清LH水平与对照小鼠相同，而FSH水平仅降低50%。雄性FSHRKO小鼠是可生育的，尽管睾丸重量明显减少。然而，睾丸抑制素A和B浓度与正常窝鼠没有差异。无突变雄性小鼠血清FSH和LH水平升高，而垂体中这些激素的含量没有差异。综上所述，如果没有FSH，卵巢卵泡的发育就不能超过前腔期。在没有成熟卵泡的情况下，卵巢雌激素水平较低，副性组织生长和促性腺激素分泌的负反馈调节受到严重损害。然而，在男性中，尽管睾丸重量减轻，垂体促性腺激素和睾丸旁分泌相互作用的反馈调节可能会受到干扰，但对FSH的无反应并不影响生育能力。
To investigate further brain-pituitary-gonadal interrelationships we have generated mice in which the gene encoding the FSH receptor has been disrupted. Female FSH receptor knockout (FSHRKO) mice were infertile. The ovaries were significantly reduced in size, with follicular development arrested at the preantral stage, but there was evidence of stromal hypertrophy. The vagina was imperforate, and the uterus was atrophic. There was no response to administration of PMSG. Inhibins A and B were undetectable in both the serum and gonads. Compared with those in control animals, serum concentrations of FSH and LH were significantly elevated in mutant females. The pituitary content of FSH, but not LH, was also significantly elevated. Estrogen administration in FSHRKO female mice suppressed serum LH levels to those seen in control mice, whereas FSH levels were reduced by only 50%. Male FSHRKO mice were fertile, although testis weight was significantly reduced. However, testicular inhibin A and B concentrations did not differ from those in normal littermates. Serum levels of FSH and LH were elevated in the null mutant male mice, whereas no differences were found in the pituitary content of these hormones. In conclusion, ovarian follicular development cannot progress beyond the preantral stage without FSH. In the absence of mature follicles ovarian estrogen remains low, and consequently accessory sex tissue growth and negative feedback regulation of gonadotropin secretion are severely compromised. In the male, however, inability to respond to FSH does not impair fertility, although testicular weight is reduced, and feedback regulation of pituitary gonadotropins and intratesticular paracrine interactions may be disturbed.