Follicle-stimulating isohormones: regulation and biological significance

Follicle-stimulating hormone (FSH) is a key hormone in the regulation of follicular development. Although the existence of FSH heterogeneity is well established, the physiological significance of this pleomorphism remains unknown. Observed changes in circulating FSH heterogeneity during critical reproductive events such as puberty and reproductive cyclicity suggest that different combinations of FSH isoforms reach the target sites during different physiological states to influence a variety of biological end points such as cellular growth, development, steroidogenesis and protein synthesis. Considering that these FSH isoforms have different physicochemical properties and potential to bind not only their cognate receptors but also structurally related, non-FSH receptors with various affinities, the regulatory implications of FSH heterogeneity in modulating the various FSH-induced functions are enormous. However, assigning functional significance to FSH heterogeneity has been hampered because of (1) difficulties associated with procurement of highly purified, naturally occurring, circulating FSH isoforms; (2) absence of reference standards that contain the entire repertoire of FSH isoforms present in biological fluids; and (3) specificity issues inherent to the detection systems used. If particular FSH isoforms do possess selective biological functions, specific combinations of FSH isoforms could be generated to regulate fertility in farm animals and humans.