Zijlstra-Westhoff W E, Slootstra J W, Puijk W C, Schaaper W M, Oonk H B, Meloen R H
Department of Molecular Recognition, ID-DLO Institute for Animal Science and Health, Lelystad, The Netherlands.
J Reprod Immunol. 1998 Jul;38(2):139-54. doi: 10.1016/s0165-0378(98)00029-1.
The aim of the present work was to define an FSH receptor (FSHR) peptide that can induce antibodies that will inhibit the bioactivity of FSH. Therefore, the hFSHR sequence was aligned with that of all other known G-protein coupled receptors. An area with increased sequence homology was identified between the FSH-, LH-, TSH receptors, the C5a receptor and the IL8 receptor. The similarity consists of a richness in acidic (D and E) and hydrophobic (Y and F) residues. In hFSHR the sequence is EDNESSYSRGFDMTYTEFDYDLCNEVVD (amino acid 299-326). Research on both the C5a- and IL8-receptor has indicated that this part is responsible for hormone binding but not for signal transduction. Protamine. an antagonist for both the C5a- and IL8 receptor also inhibited the bioactivities of FSH and LH when tested in a bioassay. This suggests that in the hFSHR this region might also be involved in hormone binding. Specificity of this region towards the diverse ligands all binding to the C5a or to the IL8 receptor might be attributed to differences in the profile of alternating basic and hydrophobic residues. Therefore, the hypothesis was tested as to whether antisera raised against peptides of this FSHR-domain would inhibit FSH-bioactivity but not LH-bioactivity. Indeed antisera were found (anti-hFSHR 309-322) that inhibited the biological activity of FSH in a bioassay. These antisera proved to be specific since they did not inhibit the bioactivity of LH. These data suggest that the core sequence (hFSHR 309-322) of the aligned domain of the hFSHR, in analogy to the IL8- and C5a receptors, is involved in hormone binding and ligand specificity. This domain therefore forms a valuable tool in FSH- and FSHR research for scientific and medical purposes.
本研究的目的是确定一种促卵泡激素受体（FSHR）肽，该肽可诱导产生能抑制FSH生物活性的抗体。因此，将人促卵泡激素受体（hFSHR）序列与所有其他已知的G蛋白偶联受体序列进行比对。在促卵泡激素（FSH）、促黄体生成素（LH）、促甲状腺激素（TSH）受体、C5a受体和白细胞介素8（IL8）受体之间鉴定出一个序列同源性增加的区域。其相似性在于富含酸性（D和E）和疏水（Y和F）残基。在hFSHR中，该序列为EDNESSYSRGFDMTYTEFDYDLCNEVVD（氨基酸299 - 326）。对C5a受体和IL8受体的研究表明，这部分负责激素结合而非信号转导。鱼精蛋白是C5a受体和IL8受体的拮抗剂，在生物测定中进行测试时，它也抑制了FSH和LH的生物活性。这表明在hFSHR中，该区域可能也参与激素结合。该区域对所有与C5a受体或IL8受体结合的不同配体的特异性，可能归因于交替出现的碱性和疏水残基分布的差异。因此，对针对该FSHR结构域肽产生的抗血清是否会抑制FSH生物活性而不抑制LH生物活性这一假设进行了验证。确实发现了（抗hFSHR 309 - 322）在生物测定中抑制FSH生物活性的抗血清。这些抗血清被证明具有特异性，因为它们不抑制LH的生物活性。这些数据表明，与IL8受体和C5a受体类似，hFSHR比对结构域的核心序列（hFSHR 309 - 322）参与激素结合和配体特异性。因此，该结构域在用于科学和医学目的的FSH和FSHR研究中形成了一种有价值的工具。
