The effect of drugs and exercise on intermediary metabolism and on the release of growth hormone and prolactin in man

Chalmers, Robert John (1977) The effect of drugs and exercise on intermediary metabolism and on the release of growth hormone and prolactin in man. PhD thesis, University of Glasgow.

Abstract

All the studies presented in this thesis involve aspects of the regulation of hGH and hPRL release. The first two sections describe studies of the effects of diphenylhydantoin (DPH) and alcohol and the third section describes studies of hypothalamic regulation of hGH and hPRL release in normal subjects and in patients with Huntington's chorea. Studies of the effects of DPH demonstrate that this drug potentiates the hGH response to exercise (Chapter 1). Glucose loading demonstrated impaired glucose tolerance and insulin release in epileptics receiving long term treatment with DPH (Chapter 2). The effect of alcohol on hypothalamic/ pituitary function was investigated by examining the effect of alcohol on hGH and hPRL release (Chapters 3, 4). Alcohol increased the hGH response to exercise in normal subjects suggesting that alcohol alters hypothalamic/pituitary regulation of hGH release. The hGH responses to exercise and insulin induced hypoglycaemia were impaired in a number of alcoholics and clinical evidence suggested that the presence of an impaired hGH response may be related to alcohol withdrawal (Chapters 5 and 6). The investigations described in Section III provide evidence that hGH and hPRL release is influenced by hypothalamic dopaminergic, noradrenergic and serotonergic receptors. The dopamine agonist bromocriptine produced significant elevation of hGH concentrations in normal subjects and suppressed both hGH and hPRL levels in a patient with acromegaly (Chapter 7). Studies of the effects of the phenothiazine derivative, fluphenazine, demonstrate that this drug elevates basal hPRL concentrations, enhances the hPRL response to insulin induced hypoglycaemia and impairs the hGH response to this stimulus (Chapters 8 and 9). These effects of fluphenazine on hGH and hPRL release are consistent with the dopamine receptor blocking properties of phenothiazine drugs. The intra-venous administration of the noradrenaline receptor agonist clonidine was associated with elevation of hGH and suppression of hPRL concentrations (Chapter 10). Administration of 5-hydroxy-L-tryptophan, the precursor of serotonin, produced a significant rise in both hGH and hPRL concentrations (Chapter 11). The regulation of release of hGH and hPRL by hypothalamic peptide factors was studied by investigating the effect of somatostatin on hormonal and metabolic changes during and after exercise in normal subjects (Chapter 12). The growth hormone release inhibiting property of this peptide was confirmed and the suppression of the hGH response did not appear to have any marked effect on fat mobilisation during exercise. The presence of an earlier hGH response to insulin induced hypoglycaemia was confirmed in patients with Huntington's chorea (Chapter 13). Further studies of the hGH and hPRL responses to bromocriptine, clonidine and 5-hydroxy-L- tryptophan in patients with this disorder demonstrated significantly reduced hGH responses to these three agents and a greater hPRL response to 5-HTP. The results do not provide evidence of increased sensitivity of hypothalamic catecholaminergic or serotonergic receptors stimulating hGH release in patients with Huntington's chorea.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: R MS Smellie
• Keywords: Pharmacology, Kinesiology, Endocrinology
• Date of Award: 1977
• Depositing User: Enlighten Team
• Unique ID: glathesis:1977-72082
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 17 May 2019 13:05
• Last Modified: 17 May 2019 13:05
• URI: https://theses.gla.ac.uk/id/eprint/72082