Probing the Frontiers of Glycoprotein Synthesis: The Fully Elaborated β-Subunit of the Human Follicle-Stimulating Hormone

摘要

The human follicle-stimulating hormone (hFSH) belongs to a family of hormones responsible for the maintenance of essential reproductive processes (gonadotropins). FSH is produced in the anterior pituitary, and the binding of FSH to its receptor stimulates the maturation of follicles and the production of estrogen in females, and maintains spermatogenesis in males. Consequently, FSH is clinically used in the treatment of anovulatory disorders associated with infertility. Administration is usually in the form of subcutaneous injections, often once a day, over prolonged periods of time. Side effects of this treatment range from allergic reactions and nausea, to mood swings and fatigue. Presently, FSH is mainly derived from recombinant technologies, specifically, from Chinese Hamster Ovary (CHO) cells. The material so obtained is a complex mixture of hormone glycoforms, that is, highly heterogeneous with respect to the carbohydrates on the peptide backbone. In normal adult humans, the FSH receptor (FSH-R) is expressed only on the ovarian granulosa cells of females and the testicular Sertoli cells of males. However, in a recent discovery it was found that the FSH-R is ubiquitously expressed on the endothelial cells of the peripheries of the tumors of the breast, prostrate, colon, pancreas, kidney, stomach, testis, and ovary. Earlier studies in mice have indicated that the effect of FSH on the growth of tumors is at least as potent as that of epidermal growth factor (EGF). Although there was a concentration dependency of this effect, what might be an interesting study of the relative roles of the various glycoforms is presently stymied by the unavailability of homogeneous forms of FSH.