Testosterone stimulates proliferation and inhibits interleukin-6 production of normal and hereditary gingival fibromatosis fibroblasts.
Hereditary gingival fibromatosis (HGF) is a rare oral condition characterized by a slow and progressive enlargement of the gingiva, involving both the maxilla and mandible. In vitro, HGF fibroblasts demonstrate a proliferative index significantly higher than fibroblasts from normal gingiva (NG). The objective of this study was to determine the effect of dihydrotestosterone on the proliferation of gingival fibroblasts derived from patients with HGF (n = 4) and from four healthy individuals. Additionally, we analyzed the effect of dihydrotestosterone on interleukin-6 (IL-6) production and determined the expression levels of androgen receptors in NG and HGF fibroblasts. Gingival fibroblasts from NG and HGF were incubated with increasing concentrations of dihydrotestosterone with or without androgen blockers, and cultured for 24 h, and the proliferation index was determined by automated cell counter. IL-6 production, in this system, was quantified using a "capture" enzyme-linked immunosorbent assay (ELISA). Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to measure the mRNA expression of androgen receptors. The results indicated that dihydrotestosterone simultaneously downregulates the production of IL-6 and upregulates the cell proliferation. Finasteride and cyprosterone acetate, two anti-androgens, partially reversed these effects. Androgen receptor mRNA expression was identified in both NG and HGF fibroblasts; however, the levels in NG were higher than those observed in HGF. These results show that testosterone coordinates the proliferation and production of IL-6 of normal and HGF fibroblasts.
Coletta
Ricardo D
RD
Department of Oral Pathology, University of Campinas Dental School, Caixa Postal 52, 13414-018 Piracicaba-SP, São Paulo, Brazil.
Reynolds
M A
MA
Martelli-Junior
H
H
Graner
E
E
Almeida
O P
OP
Sauk
J J
JJ
D058891:5-alpha Reductase Inhibitors; D000328:Adult; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000494:pharmacology; D002452:Cell Count; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D017373:Cyproterone Acetate / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005351:Fibromatosis, Gingival / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018120:Finasteride / Q000494:pharmacology; D005881:Gingiva / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D011944:Receptors, Androgen / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013223:Statistics as Topic; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015854:Up-Regulation; D000093242:Interleukin-6 Inhibitors
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D017373:Cyproterone Acetate; D013196:Dihydrotestosterone; D004791:Enzyme Inhibitors; D018120:Finasteride; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013739:Testosterone; D000093242:Interleukin-6 Inhibitors