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

Available data consistently show that untreated GH-deficient patients have decreased TBW and ECV compared to normal controls and that GH replacement normalizes these parameters as well as PV. The sodium-retaining and volume expanding effects of GH are also easily recognized in normal adults treated with GH in pharmacological dosages. In addition acromegalic patients have increased ECV which is decreased after successful surgery. Thus the antinatriuretic and volume expanding actions of anterior pituitary extracts observed for the first time more than 70 years ago are today well established. The consequence of these actions could be to adjust the internal environment and the intracellular volume to ensure optimal conditions for the various metabolic processes. The underlying mechanisms seem to be multiple and complex. The renin-angiotensin-aldosterone system plays a role, since several studies have shown stimulation of the RAAS, and this important volume regulating system is almost never suppressed by GH even during concomitant volume expansion. In addition blockade of the RAAS abolishes the volume expanding effect of GH. The activation of the RAAS could be a consequence of a renal tubular action mediated by GH or IGF-I. Alternatively, stimulation of the RAAS could be secondary to suppression of ANF, since lowering of ANF levels has been demonstrated during GH and IGF administration. In vitro studies have shown GH and IGF-I-induced down-regulation of ANF-mRNA and several studies have reported improved left ventricular function after GH and IGF-I administration. Thus one could hypothesize that a major effect of GH on human fluid homeostasis is mediated through a positive inotropic action of IGF-I on the heart, since this hormone is capable of producing sodium and fluid retention very similar to that induced by GH. The inotropic effects of IGF-I might lead to a subsequent decline in ANF release, which per se induces fluid retention, and an additional stimulation of the RAAS due to lack of the inhibitory action of ANF on this system. This theory does not obviously exclude involvement of other hormonal systems. GH itself and IGF-I have been shown to stimulate formation of Na+K+AT-Pase, but the observation that IGF-I is capable of producing fluid and sodium retention very similar to GH suggests that a major part of the actions of GH on fluid homeostasis may be mediated through IGF-I. Nitric oxide the kidney, and GH deficiency is associated with low between GH-induced fluid retention and changes in nitric oxide are lacking. Prostaglandins have been shown to be partly responsible for the renotropic action of GH and IGF-I, In view of the well-known stimulatory effect of the prostaglandins on renin release this is an interesting finding which merits further investigation in clinical studies. Excess of GH causes insulin resistance and ensuing hyperinsulinaemia, and the antinatriuretic action of insulin is undisputed. Still the role of insulin in the GH-induced changes in fluid homeostasis have been investigated less extensively than the hormonal although they may be equally important. Of special interest is possible changes in colloid and hydrostatic pressure in plasma at the capillary level and interstitial fluids. Our knowledge of the impact of GH on fluid homeostatis has improved during the last seven decades, and presently this experience is being utilized clinically in the treatment of GH-deficient patients. The complexity of the underlying mechanisms has, however, generated numerous questions, which need to be addressed in future clinical and experimental trials.