Acute and chronic effects of growth hormone on renal regulation of electrolyte and water homeostasis.
For decades, growth hormone (GH) has been known to influence electrolyte and water handling in humans and animals. However, the molecular mechanisms underlying the GH-induced anti-natriuretic and anti-diuretic effects have remained elusive. This review will examine the existing literature on renal electrolyte and water handling following acute and chronic GH-exposure. Renal responses to GH differ in acute and chronic models. Acute application of GH results in a reduced urinary electrolyte and water excretion, whereas the chronic effects of GH are more diverse, as this state likely represents a complex mixture of primary and secondary actions of GH as well as compensatory mechanisms. During chronic GH-exposure an initial sodium retaining state often occurs, followed by a normalization of the urinary sodium excretion, although extracellular volume expansion still persists. We recently described a possible mechanism by which GH acutely increases renal electrolyte and water reabsorption, by modulation of the kidney specific Na(+), K(+), 2Cl(-) co-transporter (NKCC2). The primary aim of this review is to investigate how GH-induced regulation of NKCC2 may be involved in the complex renal changes previously described during acute and chronic GH. We propose, that the GH-induced increase in NKCC2 activity may explain the initial water and sodium retention seen in a number of studies. Moreover, renal changes seen during prolonged GH-exposure may now be seen on the background of the acute stimulation of NKCC2. Additionally, GH also promotes renal acidification, thus influencing renal acid/base handling. The GH-induced renal acidification is partly compatible with changes in NKCC2 activity. Finally, we review the available data on changes in hormonal systems affecting tubular transport during acute and chronic GH-exposure.
Dimke
Henrik
H
Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University, Geert Grooteplein Zuid 30, Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands. h.dimke@ncmls.ru.nl
Flyvbjerg
Allan
A
Frische
Sebastian
S
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology* / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology*
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone