Effects of growth hormone on fluid homeostasis. Clinical and experimental aspects.

Abstract

Regulation of body fluid homeostasis appears simple at first sight since daily sodium and water intake equals daily sodium and water output. The mechanisms enabling the body to excrete exactly the ingested and metabolically produced amounts of water and sodium are, however, complex and not completely understood. The factors regulating body fluid homeostasis may grossly be divided into humoral and physical factors. The former comprises among others the renin–angiotensin–aldosterone system (RAAS), arginine vasopressin (AVP), atrial natriuretic factor (ANF), and prostaglandins. The physical factors relate primarily to renal function and factors regulating osmotic pressure. Approximately 60% of body weight is water, which may be subdivided into intracellular volume (ICV) (40%) in which potassium and phosphate are the predominant cation and anion, respectively, and extracellular volume (ECV) (20%) dominated by sodium and chloride. ECV may further be subdivided into interstitial volume(15%) and plasma volume (PV) (5%) [1]. In principle ECV constitutes the internal environment, which is responsible for the transport of ions, nutrients and hormones vital to the cells. This term was introduced by the French physiologist, Claude Bernard, in 1885. The osmotic concentrations of ECV and ICV are equal under steady-state conditions, but any change result in an osmotic gradient and an immediate flux of water along this gradient until equilibrium is restored [2]. Hence a considerable passage of water occurs across the cell membrane, exemplified by the fact that the water content of an erythrocyte is exchanged 100 times per second without any netmovement of water [3]. Water passes mainly the cell membrane through protein channels, which in turn are influenced by osmotic differences generated by facilitated diffusion and active transport across the cell membrane. A normal subject ingests 2100ml water daily and synthesizes additionally 200ml by oxidation. Daily fluid output in a normal subject includes 700ml from the skin and lungs, 200ml from faeces, and sweat and a urinary output of 1400ml [4]. Between 5 and 10% of total body water is exchanged daily in healthy adults [1]. Total body water (TBW) is traditionally estimated by isotopic dilution. ECV and PV may also be estimated using this principle, whereas ICV assessment is calculated indirectly by combining measurements of TBW and ECV. The role of GH in this complex system is not fully established, but several reports suggest that it is important in body fluid regulation. More than 70 years ago anterior pituitary extracts were shown to induce fluid retention in rats [5] and two decades later GH-induced sodium and fluid retention was also demonstrated in man [6–8]. The sodiumand water-retaining effects of GH have subsequently been confirmed in several studies in normal man, in acromegalic patients and in GH-deficient patients [9–15]. Despite methodological heterogeneity most authors seem to agree that body fluid volume is decreased in GH-deficient adults and that GH treatment normalizes body fluid volume in these patients. There is also agreement that GH causes volume expansion, when administered in pharmacological doses to normal subjects and when secreted in excess in active acromegaly. Regarding the underlying mechanisms attention has focused on direct cellular action of GH [14] and a possible GH-induced stimulation of the renin–angiotensin– aldosterone system (RAAS) [8]. More recently other hormonal systems such as ANF [15], the prostaglandins [16], IGF-I [17], and nitric oxide [18] have been suggested to be involved. At present the sodium and fluidretaining effect of GH seems indisputable, whereas the underlying mechanisms appear to be diverse. www.elsevier.com/locate/ghir Growth Hormone & IGF Research 13 (2003) 55–74