Effects of alkaline phosphatase and its inhibitor levamisole on the modulation of androgen metabolism by nicotine and minocycline in human gingival and oral periosteal fibroblasts
Abstract
Unlabelled The aim of this investigation was to establish the implications of nicotine, minocycline, alkaline phosphatase (AP) and its inhibitor levamisole (L) on tissue turnover in human gingival and periosteal fibroblasts (HGF, HPF) using [14C]-testosterone as substrate. Monolayer cultures of HGF and HPF established from four patients were incubated in duplicate with serial and optimal concentrations of nicotine and minocycline, alone and in combination, for 24h in Eagle's MEM, with the substrate [14C]-testosterone. Further experiments were carried out on HPF only, to investigate the effects of alkaline phosphatase (AP) and its inhibitor levamisole (L) on the metabolism of [14C]-testosterone, followed by the effects of L on the modulatory actions of nicotine. The cell-conditioned medium was then solvent-extracted, analysed and quantified for steroid metabolites using a radioisotope scanner. At low concentrations, nicotine stimulated the synthesis of the physiologically active androgen 5alpha-dihydrotestosterone (DHT) from [14C]-testosterone, with inhibition at higher concentrations (n=4; P Conclusion This investigation has shown that nicotine can inhibit the formation of matrix-stimulatory steroid metabolites in fibroblasts, partly due to inhibition of AP activity. Minocycline is a useful adjunct, in reducing the inhibition of androgen metabolism caused by nicotine.
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Phenytoin enhances conversion of testosterone to 5α-dihydrotestosterone in cultured gingival fibroblasts.
“Studies have shown that fibroblasts of the gingiva have the ability to metabolize testosterone to its active metabolite 5α-dihydrotestosterone, enhanced by the addition of phenytoin to the cultured fibroblasts [54].”
From An Update on the Mechanisms of Phenytoin Induced Gingival Overgrowth (2019) · cites this paper as [54]
Type 2 reductase of 5α-reductase, via production of 5α-dihydrotestosterone, has an anabolic role in gingiva by activating fibroblast cells to produce more collagen fibers or decrease collagenase activity.
“Type 2 reductase of 5α-reductase, via the production of 5α-dihydrotestosterone, has an anabolic role in gingiva by activating the fibroblast cells to produce more collagen fibers or decrease collagenase activity [54].”
From An Update on the Mechanisms of Phenytoin Induced Gingival Overgrowth (2019) · cites this paper as [54]
ECM synthesis could be enhanced by the stimulatory effect of phenytoin on the type 2 isoenzyme of 5α-reductase activity.
“ECM synthesis could be enhanced by the stimulatory effect of phenytoin on the type 2 isoenzyme of 5α-reductase activity.”
From An Update on the Mechanisms of Phenytoin Induced Gingival Overgrowth (2019) · cites this paper as [54]
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An Update on the Mechanisms of Phenytoin Induced Gingival Overgrowth
Farook, F. F., M. Nizam, M. N., & Alshammari, A. (2019) · The Open Dentistry Journal · doi:10.2174/1874210601913010430 · Cited by 18 · see citing works
“Type 2 reductase of 5α-reductase, via the production of 5α-dihydrotestosterone, has an anabolic role in gingiva by activating the fibroblast cells to produce more collagen fibers or decrease collagenase activity [54].”
Background
- Authors
- Soory, M., & Suchak, A.
- Affiliations
- Guy's and St Thomas' NHS Foundation Trust (GB)
- Guy's Hospital (GB)
- Venue
- Archives of Oral Biology
- Publisher
- Elsevier BV
- Published
- 2003-01
- Volume
- 48
- Issue
- 1
- Pages
- 69-76
- ISSN
- 0003-9969 (ISSN-L)
- OpenAlex
- W2077691762
- Cited by
- 8
- References
- 0
- Citations by year
- 2019: 1 · 2013: 1 · 2012: 2
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Oral Biology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Health Professions › Pharmacy › Oral and gingival health research
- Health Sciences › Dentistry › Periodontics › Oral Health Pathology and Treatment
- Keywords
- alkaline phosphatase, levamisole, nicotine, minocycline, androgen metabolism, dihydrotestosterone, testosterone, gingival fibroblasts, steroid metabolites, tissue turnover, enzyme inhibition
- MeSH terms
- Adult, Alkaline Phosphatase, Cells, Cultured, Dose-Response Relationship, Drug, Enzyme Inhibitors, Fibroblasts, Gingiva, Humans, Levamisole, Gas Chromatography-Mass Spectrometry, Middle Aged, Minocycline, Nicotine, Periosteum, Testosterone
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