The response of human gingival fibroblasts to interleukin-1 in their metabolic conversion of two androgenic substrates.

The effects of interleukin-1 (IL-1) on the metabolism of two androgenic substrates, testosterone and 4-androstenedione, that can be converted to the potent anabolic metabolite 5 alpha-dihydrotestosterone (DHT) were studied. Duplicate incubations of confluent gingival fibroblasts were made in Eagle's minimum essential medium + 10% fetal calf serum, with [14C]-testosterone/[14C]-androstenedione as initial substrates and optimal stimulatory concentrations of IL-1. [14C]-testosterone was converted mainly to DHT and 4-androstenedione. There was a 1.8-fold increase in DHT synthesis (n = 7; p < 0.02) and a 1.9-fold increase in 4-androstenedione in response to IL-1 (n = 7; p < 0.02) (Wilcoxon signed-rank test for non-parametric, paired observations). [14C]-4-androstenedione was mainly converted to DHT and testosterone. There was a 1.7-fold increase in DHT synthesis in response to IL-1 (n = 8; p < 0.01), and a 1.5-fold increase in testosterone formation from [14C]-4-androstenedione in the presence of IL-1, in six of the cell lines (n = 6; p < 0.05). Both testosterone and 4-androstenedione were effective substrates in forming the potent metabolite DHT in significant amounts in response to IL-1. This is significant in view of the well-documented effects of androgens on connective tissue and bone matrix, and may have implications for the healing potential of lesions in inflammatory periodontal disease.