Wunsch A, Sonntag B, Simoni M
Institute of Reproductive Medicine of the University, D-48129 Münster, Germany.
Ann Endocrinol (Paris). 2007 Jun;68(2-3):160-6. doi: 10.1016/j.ando.2007.04.006. Epub 2007 Jun 4.
Follicle-stimulating hormone (FSH) is a key factor in human reproduction. FSH activates its receptor (FSHR) located exclusively on Sertoli cells in the testis and granulosa cells in the ovary. Two common single nucleotide polymorphisms (SNP) within exon 10 of the human FSHR gene result in two almost equally common allelic variants exhibiting threonine (Thr) or alanine (Ala) at position 307 in the hinge region, respectively, asparagine (Asn) or serine (Ser) at codon 680 of the intracellular domain. Clinical studies have demonstrated that p.N680S polymorphism determines the ovarian response to FSH stimulation in patients undergoing IVF-treatment. Patients with the Ser(680) allele need more FSH during the stimulation phase to reach the serum estradiol levels of Asn(680) patients. A study investigating women with normal, mono-ovulatory menstrual cycles revealed that the Ser(680)/Ser(680) genotype leads to higher FSH serum levels and a prolonged cycle. To date, the molecular mechanism underlying the partial "resistance" of the Ser(680)-FSHR to FSH remains unclear. Future experiments should extend our current understanding of FSH action on follicular selection and dominance, thereby permitting novel, patient-tailored therapies for infertility and fertility preservation.
促卵泡激素（FSH）是人类生殖中的关键因素。FSH激活其受体（FSHR），该受体仅位于睾丸中的支持细胞和卵巢中的颗粒细胞上。人类FSHR基因第10外显子内的两种常见单核苷酸多态性（SNP）分别导致两种几乎同样常见的等位基因变体，在铰链区第307位分别表现为苏氨酸（Thr）或丙氨酸（Ala），在细胞内结构域的密码子680处分别为天冬酰胺（Asn）或丝氨酸（Ser）。临床研究表明，p.N680S多态性决定了接受体外受精治疗患者的卵巢对FSH刺激的反应。携带Ser（680）等位基因的患者在刺激阶段需要更多的FSH才能达到Asn（680）患者的血清雌二醇水平。一项针对月经周期正常、单卵泡排卵女性的研究表明，Ser（680）/Ser（680）基因型会导致更高的FSH血清水平和更长的月经周期。迄今为止，Ser（680）-FSHR对FSH产生部分“抵抗”的分子机制仍不清楚。未来的实验应扩展我们目前对FSH在卵泡选择和优势化过程中作用的理解，从而为不孕症和生育力保存提供新的、针对患者的治疗方法。
