Increased serum and bone matrix levels of transforming growth factor 1 in patients with GH deficiency in response to GH treatment

Ueland T, Lekva T, Otterdal K, Dahl TB, Olarescu NC, Jørgensen AP, Fougner KJ, Brixen K, Aukrust P, Bollerslev J
Source: Eur J Endocrinol
Publication Date: (2011)
Issue: 165(3): 393-400
Research Area:
Basic Research
Cells used in publication:
Species: human
Tissue Origin: blood
Macrophage, human
Species: human
Tissue Origin: blood
Adipocyte (pre), human
Species: human
Tissue Origin: adipose
OBJECTIVE: Patients with adult onset GH deficiency (aoGHD) have secondary osteoporosis, which is reversed by long-term GH substitution. Transforming growth factor ß1 (TGFß1 or TGFB1) is abundant in bone tissue and could mediate some effects of GH/IGFs on bone. We investigated its regulation by GH/IGF1 in vivo and in vitro. DESIGN AND METHODS: The effects of GH substitution (9-12 months, placebo controlled) on circulating and cortical bone matrix contents of TGFß1 were investigated in patients with aoGHD. The effects of GH/IGF1 on TGFß1 secretion in osteoblasts (hFOB), adipocytes, and THP-1 macrophages as well as the effects on release from platelets were investigated in vitro. RESULTS: In vivo GH substitution increased TGFß1 protein levels in cortical bone and serum. In vitro, GH/IGF1 stimulation induced a significant increase in TGFß1 secretion in hFOB. In contrast, no major effect of GH/IGF1 on TGFß1 was found in adipocytes and THP-1 macrophages. Finally, a minor modifying effect on SFLLRN-stimulated platelet release of TGFß1 was observed in the presence of IGF1. CONCLUSION: GH substitution increases TGFß1 in vivo and in vitro, and this effect could contribute to improved bone metabolism during such therapy, potentially reflecting direct effect of GH/IGF1 on bone cells.