Molecular evolution and regulation of growth hormone signaling: Toward a highly integrated control system of growth

The multifunctional nature of growth hormone (GH) results from an elaborate, multifaceted signaling system consisting of numerous types of GH and GH-family ligands binding to a variety of GH receptor (GHR) subtypes. The structural heterogeneity of GHs and GHRs results from the existence of multiple genes that arose through a series of gene duplication events during the course of teleost evolution. The presence of a particular receptor form results from tissue-specific regulation of expression, as well as from tissue-specific regulation of internalization. GHRs display distinct and overlapping binding characteristics for GH-family ligands and link to numerous different cell signaling pathways to propagate GH action. Ultimately, the response of a target cell depends on the form of GH secreted, the GHR subtype to which it binds, and the particular effector system to which that GHR links. Accumulating evidence suggests that nutritional state, season/stage of sexual maturation, and numerous hormones, including insulin (INS), GH, insulin-like growth factor I (IGF-I), somatostatins, thyroid hormones and steroids, including sex steroids, modulate these tissue-specific regulatory mechanisms and adjust the synthesis and expression of GHRs, as well as of IGF receptors to modulate growth. Such cues also may serve to coordinate growth with other processes such as metabolism, reproduction, stress and osmoregulation. This chapter discusses the complexity of this GH system in fish with specific reference to the rainbow trout Oncorhynchus mykiss.