Repetitive Stimulation of the Pituitary with Growth-Hormone-Releasing Hormone Alters the Proportion of 22 and 20 Kilodal
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Research Article Repetitive Stimulation of the Pituitary with Growth-Hormone-Releasing Hormone Alters the Proportion of 22 and 20 Kilodalton Human-Growth Hormone Released Emma A. Webb,1 P. Jane Pringle,1 Iain C. A. F. Robinson,2 and Peter C. Hindmarsh1 1 Developmental
Endocrinology Research Group, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK 2 Division of Molecular Neuroendocrinology, MRC National Institute for Medical Research, London NW7 1AA, UK Correspondence should be addressed to Emma A. Webb, [email protected] Received 13 February 2010; Accepted 2 April 2010 Academic Editor: Primus E. Mullis Copyright © 2010 Emma A. Webb et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background/Aims. 20 Kilodalton-hGH (20 K-hGH) is the second most abundant pituitary GH variant after 22 K-hGH. In the steady state the proportion of 20 : 22 K-hGH appears constant; does this proportion change with repetitive somatotroph stimulation? Methods. Forty adult males were randomised to receive a GHRH(1–29)NH2 bolus (0.5 µg/kg (n = 20) or 1.0 µg/kg (n = 20)), preceded or followed by a saline bolus, 1 week apart. Four to six weeks later, 10 subjects received 0.5 µg/kg GHRH(1–29)NH2 at 0, 60, 120, and 180 minutes. Clearance rate of 22 and 20 K-hGH was measured in 10 subjects. Results. Total amount/proportion of 22 K-hGH/20 K-hGH secreted was similar for both GHRH(1–29)NH2 doses. Repetitive stimulation reduced the amount of 22 KhGH released whereas the amount of 20 K-hGH did not change significantly leading to an increase in the proportion of 20 K-hGH (P = .05). Half-life of 20 and 22 K-hGH were not significantly different (P = .55). Conclusions. Repetitive stimulation of the somatotroph may alter the proportion of GH variant released.
1. Introduction Growth-hormone-releasing hormone (GHRH) acts on the GHRH receptor in the pituitary gland to alter the rate of GH gene transcription, increasing the amount of growth hormone produced and released [1]. GH secretion occurs immediately following a GHRH pulse, with the amount of GH released in response to an intravenous bolus dependent both on dose of GHRH and on how frequently the pituitary is stimulated with GHRH. Two main forms of GH account for most of the GH released in response to GHRH stimulation [2, 3], 22 K-hGH (191 amino acids) (approximately 75% of total secretion) and 20 K-hGH (176 amino acids) (5–10%) [4]. Numerous other forms are also detectable [5]. The 20 K-hGH version lacks residues 32–46 as a result of alternate splicing within exon 3, but retains high biological activity on the GH receptor. It may bind less tightly to the extracellular domain of the GH receptor, but appears to
have the same efficacy at the full length receptor [6]. The physiological importance of the different isoforms of GH in humans remains unclear as sensitive and specific immunoassays
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