Growing Pains: GH-induced Fibrosis Across Multiple Organs in bGH Mice

Abstract Fibrosis, excessive extracellular matrix deposition, disrupts normal tissue function. It has been observed in select tissues of individuals with acromegaly and in transgenic mouse models of acromegaly, suggesting a role of GH and/or IGF-1. However, analysis across multiple tissues and ages has not been reported. This study evaluated fibrosis in 6 tissues —lung, kidney, liver, spleen, quadriceps, and heart—from young (3 months) and aged (12-15 months) bovine GH transgenic and wild-type mice of both sexes. Fibrosis was assessed using hydroxyproline content, picrosirius red (PSR) staining, and serum biomarkers of collagen turnover (PINP, ICTP, and FAP). Hydroxyproline assays showed collagen content significantly increased with age across all tissues and both sexes. Compared to wild-type, aged male bGH mice had elevated hydroxyproline in the lung, kidney, liver, and quadriceps; aged female bGH mice showed increases in kidney, liver, and quadriceps. PSR staining showed minimal differences in young mice. In aged bGH mice, males exhibited increased PSR staining in all tissues except lung; females showed increases in all tissues except lung and heart. Serum biomarkers showed sex- and age-specific patterns: PINP decreased with age in both sexes; ICTP increased with age in both sexes; FAP was lower in bGH mice and decreased with age in females. In conclusion, excess GH promotes fibrosis in most tissues studied and becomes more pronounced with advancing age, suggesting fibrosis is a common outcome of excess GH. Whether fibrosis is directly caused by GH/IGF-1 or secondary to poor health of bGH mice requires further investigation.