Huhtaniemi I T
Department of Endocrinology and Reproduction, Erasmus University Rotterdam, The Netherlands.
Endocr Rev. 2000 Oct;21(5):551-83. doi: 10.1210/edrv.21.5.0409.
The recent unraveling of structures of genes for the gonadotropin subunits and gonadotropin receptors has provided reproductive endocrinologists with new tools to study normal and pathological functions of the hypothalamic-pituitary-gonadal axis. Rare inactivating mutations that produce distinctive phenotypes of isolated LH or FSH deficiency have been discovered in gonadotropin subunit genes. In addition, there is a common polymorphism in the LHbeta subunit gene with possible clinical significance as a contributing factor to pathologies of LH-dependent gonadal functions. Both activating and inactivating mutations have been detected in the gonadotropin receptor genes, a larger number in the LH receptor gene, but so far only a few in the gene for the FSH receptor. These mutations corroborate and extend our knowledge of clinical consequences of gonadotropin resistance and inappropriate gonadotropin action. The information obtained from human mutations has been complemented by animal models with disrupted or inappropriately activated gonadotropin ligand or receptor genes. These clinical and experimental genetic disease models form a powerful tool for exploring the physiology and pathophysiology of gonadotropin function and provide an excellent example of the power of molecular biological approaches in the study of pathogenesis of diseases.
最近，促性腺激素亚基和促性腺激素受体基因结构的解析为生殖内分泌学家提供了新工具，用以研究下丘脑 - 垂体 - 性腺轴的正常和病理功能。在促性腺激素亚基基因中发现了罕见的失活突变，这些突变会导致孤立性促黄体生成素（LH）或促卵泡生成素（FSH）缺乏的独特表型。此外，LHβ亚基基因存在一种常见的多态性，作为LH依赖性性腺功能障碍的一个促成因素，可能具有临床意义。在促性腺激素受体基因中已检测到激活和失活突变，其中LH受体基因中的突变较多，而到目前为止，FSH受体基因中的突变只有少数。这些突变证实并扩展了我们对促性腺激素抵抗和促性腺激素作用异常的临床后果的认识。从人类突变中获得的信息得到了动物模型的补充，这些动物模型的促性腺激素配体或受体基因被破坏或异常激活。这些临床和实验性遗传疾病模型构成了探索促性腺激素功能的生理学和病理生理学的有力工具，并为分子生物学方法在疾病发病机制研究中的强大作用提供了一个绝佳范例。
