Effects of Growth Hormone on Sodium Homeostasis

Abstract

Total body water constitutes about 60% of total body weight and of this, 55% is intracellular and 45% extracellular. The extracellular fluid compartment is further divided into plasma, interstitial fluid, lymph, and transcellular fluids. Since sodium (Na) is the predominant extracellular cation, regulation of extracellular volume (ECV) is tightly linked to adjustments of body Na content. The kidneys are the major organ responsible for fluid and Na homeostasis. Glomerular filtration rate (GFR) and renal plasma flow (RPF) have direct effects on the filtered load of Na, while subsequent tubular Na reabsorption is regulated chiefly by the renin-angiotensin-aldosterone system. Other hormones including atrial natriuretic peptide and antidiuretic hormone also play important roles in fluid and Na homeostasis. Growth hormone (GH) is the most abundant pituitary hormone in the adult pituitary gland. After cessation of longitudinal growth following puberty, GH continues to play a vital role in the regulation of substrate metabolism and body composition in adult life. Direct metabolic effects of GH include the stimulation of lipolysis, fat oxidation and hepatic glucose output. The anabolic actions of GH are mediated by insulin-like growth factor I (IGF-I) which promotes protein synthesis and reduces protein oxidation. Another well-known effect of GH is fluid and Na retention. Bierring and Nielsen in 1922 first reported fluid retention in rats given anterior pituitary extracts (1). The same phenomenon was observed during administration of human GH (hGH) in man by Ikkos et al (2) and later confirmed by other investigators (3-7). Further research was restricted by limited supply of hGH and the concern of possible contamination of hGH extracts by unknown bioactive substances. The availability of recombinant hGH, together with the emergence of new assays and metabolic investigative tools in the past decade, have advanced the understanding of the fluid and Na regulatory effects of GH. This chapter will review the physiological mechanisms behind the antinatriuretic and antidiuretic effects of GH, as well as the associated therapeutic implications on GH administration.