Endocrine Abstracts (2001) 2 P88

MODULATION OF ANDROGEN METABOLISM BY ALKALINE PHOSPHATASE AND ITS INHIBITION BY LEVAMISOLE IN ORAL PERIOSTEAL FIBROBLASTS

A Tilakaratne1 & M Soory2


1Dept. Periodontology, Faculty of Dental Sciences, University of Peradeniya, Sri-Lanka.; 2GKT, King's Dental Hospital, London, UK.


Alkaline phosphatase (ALP) is an important enzyme in the turnover of connective tissue and bone matrix. In view of the anabolic effects of the physiologically active androgen metabolite 5alpha dihydrotestosterone (DHT), it was relevant to investigate the effects of ALP and its inhibitor levamisole (L) on androgen metabolism in oral periosteal fibroblasts. Four cell-lines of oral periosteal fibroblasts (approved by the local Ethics Committee)were incubated in duplicate in Eagle's MEM, with 14C-testosterone and serial concentrations of ALP (1-5 micrograms/ml), L and combinations of ALP1-5 with L. After 24h, the medium was solvent extracted, the metabolites separated by thin layer chromatography and quantified using a radioisotope scanner. ALP stimulated DHT synthesis by 30-40% at concentrations of 1-4 micrograms/ml (n=4;p<0.01). L reduced DHT yields by 47% (n=4; p<0.01). The combinations of ALP with L showed 28% and 22% inhibition at the range of concentrations of ALP studied (n=4; p<0.01). The yields of 4-A showed similar trends in response to ALP, L and the combinations. Significantly high yields of DHT in response to ALP, implies its mediation in the formation of androgen metabolites. Inhibition of DHT synthesis by L and moderation in combination with ALP, confirms an ALP mediated mechanism for androgen metabolism in fibroblasts. The synthesis of physiologically active androgen metabolites by oral periosteal fibroblasts could contribute to matrix formation in these cells.

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