Interaction of follicle stimulating hormone (FSH) with its cognate receptor (FSHR) is critical for maintaining reproductive health. FSHR has a large extracellular domain (ECD), composed of leucine rich repeats (LRRs) and hinge region, a transmembrane domain (TMD) and a short C-terminal domain (CTD). In this study, we have identified a short peptidic stretch in the hinge region (hFSHR(271-275)), through extensive computational modeling, docking and MD simulations, that is capable of independently interacting with the extracellular loops of FSHR(TMD). In vitro studies revealed that FSHR(271-275) peptide increased binding of [¹²⁵I]-FSH to rat Fshr as well as FSH-induced cAMP production. Administration of FSHR(271-275) peptide in immature female rats significantly increased FSH-mediated ovarian weight gain and promoted granulosa cell proliferation. In summary, the results demonstrate that the synthetic peptide corresponding to amino acids 271-275 of hFSHR-hinge region stimulates FSH-FSHR interaction and behaves as positive allosteric modulator of FSHR. The study also lends evidence to the existing proposition that hinge region maintains the receptor in an inactive conformation in the absence of its ligand by engaging in intramolecular interactions with extracellular loops of TMD.

卵泡刺激素（FSH）与其相关受体（FSHR）的相互作用对于维持生殖健康至关重要。FSHR具有一个大的胞外域（ECD），由富含亮氨酸的重复序列（LRR）和铰链区，一个跨膜域（TMD）和一个短C端域（CTD）组成。在这项研究中，我们已经通过广泛的计算模型，对接和MD模拟，确定了铰链区（hFSHR（271-275））的短肽段延伸，能够独立地与FSHR（TMD）的细胞外环相互作用。体外研究表明，FSHR（271-275）肽增加了[ ¹²⁵I] -FSH对大鼠Fshr以及FSH诱导的cAMP产生。在未成年雌性大鼠中施用FSHR（271-275）肽可显着增加FSH介导的卵巢增重并促进颗粒细胞增殖。总之，结果表明，对应于hFSHR-铰链区氨基酸271-275的合成肽刺激FSH-FSHR相互作用并表现为FSHR的正变构调节剂。该研究还为现有的主张提供了证据，即铰链区通过与TMD的胞外环进行分子内相互作用，使受体在不存在配体的情况下保持非活性构象。