GH replacement therapy in adults stimulates fibroblast activation protein-α activity.

FAP-α activity significantly increased after GH replacement therapy in both GHD patient groups.

• In GHD group 1, FAP-α activity (RFU/min) increased from 290.6 ± 47.8 (before) to 428.5 ± 66.4 (after), P < .05.
• In GHD group 2, FAP-α activity increased from 291.0 ± 37.4 (before) to 403.0 ± 52.9 (after), P < .05.
• Both GHD groups were analyzed before and after 3-6 months of GH replacement therapy.
• Comparisons were made against non-GHD hypopituitary patients and a healthy reference group.

FAP-α levels significantly increased by 40% after GH replacement therapy in both GHD groups.

• FAP-α levels increased by 40% after GH replacement in both groups (P < .01).
• FAP-α levels correlated closely with FAP-α activity.
• The increase was observed across both GHD patient groups studied.

Collagen turnover biomarkers PINP, PIIINP, and CTx all significantly increased after 3 months of GH replacement therapy.

• PINP (procollagen type I N-terminal propeptide), PIIINP (procollagen type III N-terminal propeptide), and CTx (C-terminal telopeptide of type I collagen) were measured as collagen turnover biomarkers.
• All three biomarkers significantly increased after 3 months of GH replacement.
• The increase in these collagen turnover markers was concurrent with the increase in FAP-α activity and levels.

Intact FGF21 levels remained unchanged after GH replacement therapy despite increased FAP-α activity.

• Intact FGF21 is a known substrate of FAP-α, and its cleavage by FAP-α would reduce intact FGF21 levels.
• The lack of change in intact FGF21 suggests that GH-driven FAP-α activity predominantly involves collagen breakdown rather than FGF21 cleavage.
• This finding differentiates the substrate preference of GH-stimulated FAP-α activity in this context.

FAP-α levels are reversibly elevated in active acromegaly, providing prior context for the GH-FAP-α relationship.

• Elevated FAP-α levels in acromegaly are described as reversibly elevated, suggesting a direct GH/IGF-I-mediated effect.
• This background finding motivated the investigation of GH replacement therapy effects on FAP-α in GHD patients.
• FAP-α is a serine protease whose substrates include collagen and fibroblast growth factor 21 (FGF21).

FAP-α is proposed as a novel biomarker of GH/IGF-I activity and may be causally linked to GH-induced fibrosis.

• The authors state this is the first documentation that GH stimulates FAP-α activity in vivo in human subjects.
• FAP-α is identified as a novel biomarker of GH/IGF-I activity based on the observed increases following GH replacement.
• GH is noted to potentially promote fibrosis in adults, and FAP-α may be causally linked to this process.
• GH potently stimulates collagen turnover, which underlies its anabolic effects on bone in children.