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PubMed · 2899643

Growth hormone and its modulation.

Abstract

Our knowledge of the mechanisms involved in the regulation of somatotroph cell growth is scanty and much work is still needed to elucidate the role of different growth factors and the mechanisms involved in oncogene activation in both normal and tumour cell growth. However, there are several recent, important clinical ramifications from our improved understanding of GH neuroregulation. The use of long-acting SS analogues is valuable in the treatment of acromegaly, probably in acute variceal haemorrhage and it also produces symptomatic improvement in patients with vipomas and glucagonomas. GHRH may be of value in the treatment of short stature due to hypothalamic GHRH deficiency but further definitive studies are now required to provide convincing evidence that this line of treatment is of greater benefit than the use of synthetic recombinant human GH. Inhibition of GH release may be of value in prevention of both acute and chronic complications of insulin-dependent diabetes mellitus. The use of cholinergic muscarinic receptor blockade in this context may be particularly useful because of a probably sparing of the counter-regulatory GH response to hypoglycaemia. In view of the relative ease with which nocturnal GH secretion can be abolished, we think it reasonable to consider the possible existence of a permissive or mediating role of GH in other disease states, either directly or by maintaining production of either local tissue or circulating growth factors or both.

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BibTeXRIS

C Dieguez, M D Page, J R Peters, M F Scanlon. 1988. Growth hormone and its modulation.. https://pubmed.ncbi.nlm.nih.gov/2899643/

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Protein metabolism in acromegaly: differential effects of short- and long-term treatment.

CONTEXT: GH acutely increases body protein by stimulating protein synthesis and reducing protein oxidation. OBJECTIVE: The objective of the study was to determine whether these changes in protein metabolism are sustained in long-term GH excess and reversed by correction. DESIGN: We conducted a cross-sectional study in 16 acromegalic and 18 normal subjects and a longitudinal study in which acromegalic subjects were studied before and after short-term (n=8) or long-term (n=10) treatment. SETTING: The study was conducted at a clinical research center. MAIN OUTCOME MEASURES: Whole-body rates of leucine appearance (leucine Ra; an index of protein breakdown), leucine oxidation, and nonoxidative leucine disposal (NOLD; an index of protein synthesis) estimated using infusion of 1-[13C] leucine were measured. RESULTS: Leucine Ra and NOLD were greater (P<0.01) in acromegalic compared with normal subjects, whereas leucine oxidation did not differ. Leucine oxidation increased significantly (P<0.05) after short-term treatment but returned to baseline after long-term treatment. Both leucine Ra and NOLD decreased significantly (P<0.05) after short- and long-term treatment. Adjustment for body composition did not affect results. CONCLUSIONS: In acromegalic subjects, protein breakdown and synthesis are increased, whereas protein oxidation does not differ from normal subjects. Protein oxidation increases transiently, whereas protein breakdown and synthesis are stably reduced after treatment. Because protein oxidation represents irreversible loss, we conclude that the normal state of protein oxidation found in acromegaly and after long-term treatment represents metabolic adaptation, which maintains protein mass at a steady state after stable changes in GH status.

Acromegaly↗

Acromegaly.

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Acromegaly↗

Carney complex: the first 20 years.

PURPOSE OF REVIEW: The purpose of this review is to comment on the current findings on Carney complex, a dominantly inherited disease and a unique multiple endocrine neoplasia syndrome. RECENT FINDINGS: Sequencing of the PRKAR1A gene in more than 150 kindreds has revealed a number of pathogenic mutations; in more than 90% of the cases, the sequence change was predicted to lead to a premature stop codon and, thus, mutant mRNAs were subject to nonsense-mediated mRNA decay. In Carney complex syndrome cells carrying these mutations, protein kinase A activity is irregularly stimulated by cAMP. Mutations that did not lead to a premature stop codon have also been described; these were also associated with abnormal protein kinase A activity. Animal models of the disease have been recently developed; they reproduced some of the stigmata of Carney complex syndrome but not all. Genetic testing of patients' family members has been introduced in recent years, leading to early detection and a better overall prognosis. SUMMARY: New treatments have yet to be applied; the elucidation of the molecular pathways regulated by PRKAR1A holds the promise of leading to molecularly designed therapies.

Acromegaly↗