Growth Hormone and Cerebral Amyloidosis

S. Benvenga; F. Guarneri

doi:10.1055/s-0042-103753

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2016; 48(08): 520-522
DOI: 10.1055/s-0042-103753

Endocrine Care

Growth Hormone and Cerebral Amyloidosis

S. Benvenga

¹Department of Clinical and Experimental Medicine – Endocrinology, University of Messina, Policlinico “Gaetano Martino”, pad. H, Via Consolare Valeria – Gazzi, Messina, Italy

²Master Program on Childhood, Adolescent and Women’s Endocrine Health, University of Messina, Policlinico “Gaetano Martino”, pad. H, Via Consolare Valeria – Gazzi, Messina, Italy

³Interdepartmental Program on Molecular & Clinical Endocrinology and Women’s Endocrine Health, Policlinico “Gaetano Martino”, pad. H, Via Consolare Valeria – Gazzi, Messina, Italy

,

F. Guarneri

⁴Department of Clinical and Experimental Medicine – Dermatology, University of Messina, Policlinico “Gaetano Martino”, pad. H, Via Consolare Valeria – Gazzi, Messina, Italy

› Author Affiliations

Abstract

Great interest has recently been focused on a paper reporting characteristic deposits of amyloid-β protein associated with Alzheimer’s disease in brains of adults who died of Creutzfeldt-Jakob disease. As they had contracted such disease after treatment with prion-contaminated human growth hormone extracted from cadaver-derived pituitaries, the authors have suggested that interhuman transmission of Alzheimer’s disease had occurred. Our previous research led us to find that amyloid-forming peptides share amino acid sequence homology, summarized by a motif. Here, we probed the amino acid sequence of human growth hormone for such a motif, and found that 2 segments fit the motif and are potentially amyloid-forming. This finding was confirmed by Aggrescan, another well-known software for the prediction of amyloidogenic peptides. Our results, taken together with data from the literature that are missing in the aforementioned paper and associated commentaries, minimize the contagious nature of the iatrogenically-acquired coexistence of Creutzfeldt-Jakob disease and Alzheimer’s disease. In particular, the above mentioned paper misses literature data on intratumoral amyloidosis in growth hormone- and prolactin-secreting adenomas, tumors relatively frequent in adults, which are often silent. It cannot be excluded that some pituitaries used to extract growth hormone contained clinically silent microadenomas, a fraction of which containing amyloid deposits, and patients might had received a fraction of growth hormone (with or without prolactin) that already was an amyloid seed. The intrinsic amyloidogenicity of growth hormone, in the presence of contaminating prion protein (and perhaps prolactin as well) and amyloid-β contained in some cadavers’ pituitaries, may have led to the observed co-occurring of Creutzfeldt–Jakob disease and Alzheimer’s disease.

Key words

somatotropin - amyloid - Alzheimer’s disease - bioinformatics - pituitary - microadenomas

Full Text

References

References
1 Jaunmuktane Z, Mead S, Ellis M, Wadsworth JD, Nicoll AJ, Kenny J, Launchbury F, Linehan J, Richard-Loendt A, Walker AS, Rudge P, Collinge J, Brandner S. Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy. Nature 2015; 525: 247-250
2 Eisele YS, Obermüller U, Heilbronner G, Baumann F, Kaeser SA, Wolburg H, Walker LC, Staufenbiel M, Heikenwalder M, Jucker M. Peripherally applied Abeta-containing inoculates induce cerebral beta-amyloidosis. Science 2010; 330: 980-982
3 Guarneri F, Cannavò SP, Benvenga S. Cutaneous amyloidoses: a minimum common denominator in their amino acid sequence. Comput Biol Med 2014; 50: 14-18
4 Guarneri F, Guarneri B. Analisi bioinformatica della suscettibilità genetica HLA-linked a malattie immunoallergiche: il software MotiFinder. Ann Ital Dermatol Allergol 2010; 64: 69-75
5 Conchillo-Solé O, de Groot NS, Avilés FX, Vendrell J, Daura X, Ventura S. AGGRESCAN: a server for the prediction and evaluation of "hot spots" of aggregation in polypeptides. BMC Bioinformatics 2007; 8: 65
6 Irwin DJ, Abrams JY, Schonberger LB, Leschek EW, Mills JL, Lee VM, Trojanowski JQ. Evaluation of potential infectivity of Alzheimer and Parkinson disease proteins in recipients of cadaver-derived human growth hormone. JAMA Neurol 2013; 70: 462-468
7 Krebs MR, Macphee CE, Miller AF, Dunlop IE, Dobson CM, Donald AM. The formation of spherulites by amyloid fibrils of bovine insulin. Proc Natl Acad Sci USA 2004; 101: 14420-14424
8 Dische FE, Wernstedt C, Westermark GT, Westermark P, Pepys MB, Rennie JA, Gilbey SG, Watkins PJ. Insulin as an amyloid-fibril protein at sites of repeated insulin injections in a diabetic patient. Diabetologia 1988; 31: 158-161
9 Sie MP, van der Wiel HE, Smedts FM, de Boer AC. Human recombinant insulin and amyloidosis: an unexpected association. Neth J Med 2010; 68: 138-140
10 Saitoh Y, Mori H, Matsumoto K, Ushio Y, Hayakawa T, Mori S, Arita N, Mogami H. Accumulation of amyloid in pituitary adenomas. Acta Neuropathol 1985; 68: 87-92
11 Benvenga S, Cannavò S, Trimarchi F. Prolactin is an amyloid-related protein. J Endocrinol Invest 2004; 27: 209-210
12 Gupta Y, Singla G, Singla R. Insulin-derived amyloidosis. Indian J Endocrinol Metab 2015; 19: 174-177
13 Westermark P, Grimelius L, Polak JM, Larsson LI, Van Noorden S, Wilander E, Pearse AG. Amyloid in polypeptide hormone-producing tumors. Lab Invest 1977; 37: 212-215
14 Mori H, Mori S, Saitoh Y, Moriwaki K, Iida S, Matsumoto K. Growth hormone-producing pituitary adenoma with crystal-like amyloid immunohistochemically positive for growth hormone. Cancer 1985; 55: 96-102
15 Hinton DR, Polk RK, Linse KD, Weiss MH, Kovacs K, Garner JA. Characterization of spherical amyloid protein from a prolactin-producing pituitary adenoma. Acta Neuropathol 1997; 93: 43-49
16 Freda PU, Beckers AM, Katznelson L, Molitch ME, Montori VM, Post KD, Vance ML. Endocrine Society. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2011; 96: 894-904
17 Pan W, Yu Y, Cain CM, Nyberg F, Couraud PO, Kastin AJ. Permeation of growth hormone across the blood-brain barrier. Endocrinology 2005; 146: 4898-4904