Androgen metabolism in response to oestradiol-17beta and progesterone in human gingival fibroblasts (HGF) in culture.

Abstract

The modulation of androgen metabolism by oestrogen and progesterone in HGF has been investigated, to elucidate hormone modulatory mechanisms, in periodontal disease presentation and healing responses. Duplicate incubations of HGF were performed in Eagle's MEM for 24 h with either 14C-testosterone/14C-4-androstenedione as substrate and serial concentrations of oestradiol-17beta, or progesterone (0.01-50 microg/ml). The effect of the anti- oestrogen tamoxifen on the action of oestradiol in HGF was also investigated. The medium was analysed and quantified for steroid metabolites. When 14C-testosterone was used as substrate, oestradiol stimulated the synthesis of 5alpha-dihydrotestosterone (DHT), 4- androstenedione (4-A) and the diols by 35%, 25% and 2-10-fold respectively (n=4; p<0.01), at optimal concentrations. Tamoxifen inhibited the stimulatory effects of oestradiol. Similarly, when 14C-4-androstenedione was used as substrate, there were 60% and 2-fold increases in the yields of DHT and testosterone respectively, with significant increases in the formation of the diols in response to oestradiol (n=4; p<0.001). Progesterone inhibited the formation of DHT and 4-A by 10-fold and 3-5-fold at effective inhibitory concentrations (n=4; p<0.001), when 14C- testosterone was used as substrate. Similarly, when 14C-4-androstenedione was used as substrate, progesterone decreased the yields of testosterone, DHT and the diols substantially. These results reinforce the potentially anabolic and catabolic roles of oestradiol and progesterone, respectively. This may partly explain the modulatory mechanisms involved, in periodontal disease presentation during altered hormonal states and healing responses in the inflamed periodontium.