The effect of PDGF, TGF-beta and IGF in combination on androgen metabolism by fibroblasts.
The aim of this investigation is to study growth factor combinations (PDGF/IGF PDGF/TGF-beta and TGF-beta/IGF) on the metabolism of 2 androgen substrates 14C-testosterone/14C-4-androstenedione to the matrix stimulatory androgen 5alpha-dihydrotestosterone (DHT). Human gingival fibroblasts in culture were incubated in Eagle's MEM with the radiolabelled substrates and growth factors for 24 h, when the medium was extracted and analysed for radioactive metabolites. When 14C-testosterone was used as substrate, there was an 80% increase in DHT synthesis over controls with the PDGF/IGF combination (n=7; p<0.01), which was less than the effects of each of the growth factors alone. Similarly, PDGF/TGF-beta resulted in a 2-fold increase in DHT synthesis over controls (n=5; p<0.01) which compared with individual PDGF incubations, and the TGF-beta/IGF combination resulted in a 30% increase in DHT synthesis over controls (n=3; p<0.01); this was less than the 2.8/2.5-fold increases produced individually. Similarly, when 14C-4-androstenedione was used as the substrate, there were 2-fold increases in DHT synthesis in response to combinations of PDGF/IGF and PDGF/TGF-beta (n=5; p<0.01). These results demonstrate feedback inhibition when individually active growth factors function in combination; this may be indicative of mechanisms for physiological homeostasis seen in vivo.
Kasasa
S C
SC
Department of Periodontology, King's College School of Medicine and Dentistry, London, UK.
Soory
M
M
D000735:Androstenedione / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000032:analysis / Q000378:metabolism; D004338:Drug Combinations; D005246:Feedback; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000008:administration & dosage / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D019275:Radiopharmaceuticals; D013739:Testosterone / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*
D002250:Carbon Radioisotopes; D004338:Drug Combinations; D010982:Platelet-Derived Growth Factor; D019275:Radiopharmaceuticals; D016212:Transforming Growth Factor beta; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; D007335:Insulin-Like Growth Factor II