In Vivo and In Vitro Effects of Human Growth Hormone on Rat Intestinal Ion Transport

Abstract

It has been reported that: I ) ovine growth hormone stimulates intestinal water, sodium, and chloride absorption and 2) specific growth hormone receptors are present in the rat intestine. Aims of this work were to investigate the effects of acute administration of hGH on water and ion transport in the rat ileum in vivo and in vitro. In vivo, the absorption rates of water, sodium, chloride, and potassium were determined in the rat perfused ileum, during a basal period and after i.v. administration of 6 Mg/kg recombinant DNA-derived hGH. In vitro , electrical parameters were measured before and after the hormone addition to the mucosal or the serosal side of rat ileal mucosa mounted in Ussing chambers. In vivo, growth hormone induced a rapid increase in the absorption rates of water, sodium, chloride, and potassium. In vitro, the serosal, but not the mucosal, addition of growth hormone induced a rapid decrease of transepithelial potential difference and of short-circuit current. The effect was time-and dose-dependent, saturable, but not reversible in the short time. The electrical'effect was abolished in the absence of The ability of GH to induce fluid retenti on is well established , but the mechanisms of this effect are not well und erstood (1). Most studies have focused on the interr elationships between various hormones taking part to the complex network that regulates Na + balance and on the renal effects of GH (1).It is now known that the intestine plays an important role in the regulation of body fluid home ostasis (2). GH has several effects at the intestinal level. In fact, it stimulates intestinal growth and differentiation (3, 4), vitamin D-dep endent Ca 2 + binding protein synthesis (5), and Ca 2 + absorption (6). Furthermore, GH increases the gastrin and somatostatin contents of rat stom ach ,(7). Finally, it has been previousl y shown that high doses of ovine GH, given to rats for 2 d in vivo, incre ased the absorption rates of H 2 0 and electrolytes as measured by intestinal everted sacs (8). chloride, indicating that it was related, at least in part, to inhibition of basal active chloride secretion. Growth hormone also reduced the short-circuit current increase induced by the secretagogues Escher ichia coli heat-stable enterotoxin, theophylline, and calcium ionophore A23187. These results indicate that hGH has a rapid absorptive effect that is related, at least in part, to a direct intestinal antisecretory mechanism. It also reduces active intestinal secretion induced by various secretagogues. (Pediatr Res 37: 576-580, 1995) Abbreviations GH , growth hormone r·hGH, recombinant DNA-derived hGH Isc, short-circuit current PD, transepithelial potential difference G, tissue conductance ST, Escherichia coli heat-stable enterotoxin tionally believed to be mediat ed by GH-dep endent production of mediators such as IGF-I (9, 10). Howe ver, it has been report ed that IGF-I does not cause fluid retention (11). Recently GH has been shown to inhibit the production of the atrial natriuretic peptid e (12) . I...

Effect of Recombinant Human Growth Hormone on Intestinal Absorption and Body Composition in Children With Short Bowel Syndrome

“…Interestingly, the stool volume did not increase, despite a significant increase in oral and/or enteral intakes during rhGH treatment. This suggest that one of the main effects of rhGH in these SBS patients might be the enhancement of the transport of water, ions, and nutrients, as previously reported by Guarino et al 60 and Canani et al 61 with in vitro and in vivo models of intestinal absorption.…”

“…In the present study, both clinical findings (PN reduction mostly limited to rhGH treatment period) and biological data (plasma citrulline, net energy balance) suggest that rhGH produced its main effects during its administration. Beside the effects cited above, GH is known to promote water and electrolyte transport through tyrosine kinase in human intestinal cells 60 . A study performed in children with severe intractable diarrhea treated with rhGH showed a significant reduction of water electrolyte losses 61 .…”

Effect of exercise on key pharmacokinetic parameters related to metformin absorption in healthy humans: A pilot study

“…Another possibility is the decreased intestinal motility caused by exercise, as a result of which metformin may have dwelled in the small intestine for a longer time. A third explanation could be that intestinal ion fluxes are regulated by several agents, such as growth hormone (GH), which increases basal intestinal water and ion absorption, directly interacting with the enterocyte in in vivo and in vitro animal models . High‐intensity exercise increases serum GH concentration in humans, and this response is not affected by the ingestion of glucose prior to exercise .…”

“…A third explanation could be that intestinal ion fluxes are regulated by several agents, such as growth hormone (GH), which increases basal intestinal water and ion absorption, directly interacting with the enterocyte in in vivo and in vitro animal models. [35][36][37] High-intensity exercise increases serum GH concentration in humans, and this response is not affected by the ingestion of glucose prior to exercise. 38 Thus, an exercise-induced increase in GH could stimulate metformin intestinal absorption through the modulation of cationic transporters in the apical membrane of the enterocyte.…”

Effect of high dose growth hormone with glutamine and no change in diet on intestinal absorption in short bowel patients: a randomised, double blind, crossover, placebo controlled study

“…Growth hormone has been shown to increase intestinal growth and promote adaptation in animal models 1. Glutamine is an important nutrient for enterocytes and is associated with maintenance of mucosal integrity and intestinal adaptation in animals 2.…”