Many of the anabolic effects of growth hormone (GH) are indirect, occurring through GH-stimulated production of insulin-like growth factor-I (IGF-I) by the liver. As well as being GH regulated, plasma IGF-I concentrations have been demonstrated to be dependent upon protein nutrition, with low protein diets being associated with reduced plasma IGF-I concentrations. This effect cannot be reversed by GH, suggesting that liver sensitivity to GH is impaired. To investigate the mechanisms through which protein supply affects GH sensitivity, primary cultures of ovine hepatocytes were grown in defined media. In a first experiment the media contained various fractions (0.2, 1.0, 5.0) of portal vein amino acid concentrations in fed sheep. In the second 24h incubation period, unstimulated IGF-I secretion was highly sensitive the concentration of amino acids in the media, with significantly greater release of basal IGF-I in 5x compared to either 1x (P<0.05) or 0.2x amino acid containing media. In a second series of experiments the effects of specific amino acid depletions was examined. Methionine depletion of 0.2x portal amino acid concentrations ablated the GH response second 24h of culture without affecting basal IGF-I release. By comparison <sup>3</sup>H-leucine incorporation into secreted protein, following 20 hours of culture in defined media was significantly reduced in 0.2x aa (P<0.01) and 1.0x aa (P<0.05) media compared with 5.0x aa media, however secretory protein synthesis was unaffected by methionine depletion to 0.2x portal concentrations. The results suggest that amino acid availability regulates both basal and GH stimulated IGF-I release in ovine hepatocytes. Furthermore reducing methionine concentrations in the culture media to 0.2x portal concentrations diminishes GH response without compromising protein secretion.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:548715 |
| Date | January 1999 |
| Creators | Wheelhouse, Nicholas Mark |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=185765 |
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