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

Area of Science:

• Endocrinology
• Pathology
• Animal Models

Background:

• Fibrosis, characterized by excessive extracellular matrix deposition, impairs tissue function.
• Acromegaly and its associated growth hormone (GH) and insulin-like growth factor-1 (IGF-1) signaling are implicated in fibrosis.
• Comprehensive multi-tissue and age-based analyses of GH-induced fibrosis are lacking.

Purpose of the Study:

• To evaluate fibrosis in six tissues (lung, kidney, liver, spleen, quadriceps, heart) of young and aged bovine GH (bGH) transgenic and wild-type mice.
• To assess the impact of age, sex, and GH excess on collagen content and turnover.

Main Methods:

• Hydroxyproline content assays to quantify collagen.
• Picrosirius Red (PSR) staining for collagen visualization.
• Serum biomarkers (PINP, ICTP, FAP) for collagen turnover assessment.

Main Results:

• Collagen content significantly increased with age across all tissues and sexes.
• Aged male bGH mice showed elevated collagen in lung, kidney, liver, and quadriceps; aged females showed increases in kidney, liver, and quadriceps.
• PSR staining revealed increased fibrosis in aged bGH mice, with sex-specific patterns, while serum biomarkers indicated age- and sex-specific collagen turnover changes.

Conclusions:

• Excess GH significantly promotes fibrosis in most studied tissues, with effects becoming more pronounced with age.
• Fibrosis is a common outcome of GH excess, though direct causality versus secondary effects requires further investigation.
• Age and sex are critical factors modulating GH-induced fibrotic responses.