As mentioned in the introduction to this chapter, a catalog of the biological actions of the FGFs in all their cell types, both embryonic and adult, is not possible in this chapter. However, there are two aspects of FGF biological activity upon which some comment is appropriate.
The endocrine FGFs have, in the adult organism, specific physiological roles as do the other hormones discussed through this book. For example, the crucial actions of FGF23, interacting with FGFR1c and α- klotho, in the control of phosphate and therefore bone metabolism. FGF19, the main receptor for which is FGFR4 with β-klotho, is part of a negative feedback loop regulating bile acid synthesis following a meal. FGF21 binding to FGFR1c and β-klotho provides, under fasting conditions, a signal from the liver to the adipose tissue to increase fatty acid release and oxidation, gluconeogenesis, ketogenesis.
The second aspect of the biological activities of the FGF family of growth factors to emphasize is not unique to this family. This is that amplification of their nor mal signaling activity can and does lead to unrestrained growth of the cells in which this occurs. This can be due to a number of events, described more in section VII, including mutations in the receptor which render them constitutively active. For example, one naturally occur ring mutation in FGFR1, leading to the absence of IgG loop D1, behaves in such a way.
