{"title":"Follicle-stimulating hormone sweetness: How carbohydrate structures impact on the biological function of the hormone","authors":"","doi":"10.1016/j.arcmed.2024.103091","DOIUrl":null,"url":null,"abstract":"<div><div>Follicle-stimulating hormone (FSH), or follitropin, exists in multiple molecular forms due largely to its protein-carbohydrate composition and the complexity of the glycans attached to the protein core. The heterogeneity of gonadotropins exists in two forms, macroheterogeneity, which results from the absence of one or two oligosaccharide chains in the ß-subunit, and microheterogeneity which results from variation in the structures and complexity of the glycans attached to the hormone. In the clinical arena, FSH compounds are widely used by fertility specialists to promote ovarian follicle growth and maturation to a preovulatory follicle containing a fertilization-competent oocyte. Several genetically engineered recombinant human FSH preparations have been added to the arsenal of follitropin preparations in several countries for the treatment of infertility, particularly in women attending assisted reproduction clinics. Although the primary structure of these recombinant proteins is identical to that of naturally occurring FSH, the cell context and variations in the production and purification processes may impact the glycosidic profile of the recombinant FSH macro- and micro-heterogeneity, which may potentially influence the pharmacokinetics and pharmacodynamics of the compound. This review concentrates on the structure-function correlates of follitropin, with emphasis on the physiological and biological importance of the carbohydrates attached to its protein core, including its pharmacokinetics and biological activity. Emphasis is placed on pituitary FSH, and the available data on the various recombinant FSH preparations employed in therapeutics are also discussed, considering that this gonadotropin represents the cornerstone for the treatment of infertility in modern assisted reproduction.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Medical Research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0188440924001437","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Follicle-stimulating hormone (FSH), or follitropin, exists in multiple molecular forms due largely to its protein-carbohydrate composition and the complexity of the glycans attached to the protein core. The heterogeneity of gonadotropins exists in two forms, macroheterogeneity, which results from the absence of one or two oligosaccharide chains in the ß-subunit, and microheterogeneity which results from variation in the structures and complexity of the glycans attached to the hormone. In the clinical arena, FSH compounds are widely used by fertility specialists to promote ovarian follicle growth and maturation to a preovulatory follicle containing a fertilization-competent oocyte. Several genetically engineered recombinant human FSH preparations have been added to the arsenal of follitropin preparations in several countries for the treatment of infertility, particularly in women attending assisted reproduction clinics. Although the primary structure of these recombinant proteins is identical to that of naturally occurring FSH, the cell context and variations in the production and purification processes may impact the glycosidic profile of the recombinant FSH macro- and micro-heterogeneity, which may potentially influence the pharmacokinetics and pharmacodynamics of the compound. This review concentrates on the structure-function correlates of follitropin, with emphasis on the physiological and biological importance of the carbohydrates attached to its protein core, including its pharmacokinetics and biological activity. Emphasis is placed on pituitary FSH, and the available data on the various recombinant FSH preparations employed in therapeutics are also discussed, considering that this gonadotropin represents the cornerstone for the treatment of infertility in modern assisted reproduction.
期刊介绍:
Archives of Medical Research serves as a platform for publishing original peer-reviewed medical research, aiming to bridge gaps created by medical specialization. The journal covers three main categories - biomedical, clinical, and epidemiological contributions, along with review articles and preliminary communications. With an international scope, it presents the study of diseases from diverse perspectives, offering the medical community original investigations ranging from molecular biology to clinical epidemiology in a single publication.