Abstract
In our previous publication, it was shown that growth hormone (GH) excess in acromegaly affects the cell integrity of somatic cells through increased DNA damage throughout the body and impaired DNA repair pathways. Acromegaly is a hormone disorder pathological condition that develops as a result of growth hormone over-secretion from the pituitary gland. We produced a zebrafish acromegaly model to gain a better understanding of the excess GH effects at the cellular level. Here we show that the acromegaly zebrafish model progressively reduced the number of stem cells in different organs and increased oxidative stress in stem cells. Importantly, the decline in the stem cells was even more apparent than in aged fish. The controversy and debate over the use of GH as an anti-aging therapy have been going on for several years. In this study, excess GH induced aging signs such as increased senescence-associated (SA)-β-galactosidase staining of abdominal skin and similarity of the pattern of gene expression between aged and acromegaly zebrafish. Thus, this study highlights the role of excess GH in acromegaly stem cells.
Highlights
In early life, the blood level of growth hormone (GH) is high, corresponding to rapid somatic growth.Its level gradually declines during adult life and aging
The SP phenotype has frequently been used for the identification of adult stem cells in various human and mouse organs [16,17,18], until now, it has only been used in zebrafish for the isolation of hematopoietic stem cells (HSCs) [18], so we firstly focused on the quantification of the HSCs
To verify that the SP stem cell had been isolated by the Fluorescence-activated cell sorting (FACS), verapamil was used with the Hoechst 33342 stain as a negative control because it is an inhibitor of ATP-binding cassette (ABC) transporters
Summary
Its level gradually declines during adult life and aging. Age-related symptoms such as muscle mass reduction have been associated with somatopause; GH therapy has been used as an antiaging drug. Studies showed that GH treatment of men over 65 years of age significantly increased muscle mass, increased bone mineral density, and reduced adiposity [3]. Such findings do not suggest, that GH administration improves longevity. GH deficiency syndrome (Laron dwarfism) is associated with a significant reduction in pro-aging signaling, cancer, and diabetes [5]
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