Endocrine Abstracts

Background: GH potently stimulates collagen turnover which underlies its anabolic effects on bone in children, whereas it may promote fibrosis in adults. Fibroblast activation protein-α (FAPα) is involved in collagen turnover by its collagen-cleaving and fibroblast-stimulating activity, which predominantly is expressed in association with fibrosis. FAPα also cleaves and inactivates fibroblast growth factor 21 (FGF21), a multi-faceted metabolic hormone. We have previously recorded elevated FAPα protein levels in uncontrolled acromegaly but it remains to be studied if FAPα activity is GH-dependent.

Aim: To prospectively measure serum FAPα levels and activity, FGF21, and collagen turnover biomarkers in patients with acromegaly at time of diagnosis and after treatment.

Methods: Using immunoassays and an activity assay, we measured FAPα levels and activity, total and intact FGF21, PINP, PIIINP and CTx in serum from 15 acromegaly patients before and after treatment.

Results: Serum FAPα protein levels (μg/l) and enzymatic activity (RFU/min) decreased by 35% (101.7 ±9.4 [before] vs 63.1 ±5.9 [after] (mean ±SEM); P<0.001) and 34% (373.2 ±26.5 [before] vs 248.3 ±14.9 [after]; P<0.0001) after treatment, respectively. Serum PINP, PIIINP and CTx levels decreased by 60% (P<0.001), 69% (P<0.01) and 53% (P<0.001) after treatment, respectively. The change in FAPα protein levels before and after treatment correlated positively with the change in FAPα activity before and after treatment (r=0.74; P<0.01).

Conclusion: 1. Our study document for the first time that GH stimulates FAPα activity in human subjects in vivo.2. The concomitant increase in markers of collagen turnover and the lack of change in FGF21 suggest that GH-driven FAPα activity predominantly involves collagen breakdown.3. FAPα is a novel and promising biomarker of GH/IGF-I activity and may be causally linked to GH-induced fibrosis.