The role of androgens on periodontal repair in female rats

Author(s)

Steffens, Joao Paulo ^[1] ; Leal Santana, Luis Carlos ^[2] ; Paiva Pitombo, Jonleno Coutinho ^[2] ; Ribeiro, Daniel Olivio ^[2] ; Costa Albaricci, Maria Carolina ^[2] ; Cubas Warnavin, Stephanie von Stein ^[1] ; Kantarci, Alpdogan ^[3] ; Spolidorio, Luis Carlos ^[2]

Affiliation

^[1] Univ Fed Parana UFPR, Dept Stomatol, Curitiba, PR - Brazil

^[2] Univ Estadual Paulista UNESP, Sch Dent Araraquara, Dept Physiol & Pathol, Araraquara, SP - Brazil

^[3] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA - USA

• Document type: Journal article
• Source: Journal of Periodontology; v. 89, n. 4, p. 486-495, APR 2018.
• Web of Science Citations: 1

Abstract

Background: Testosterone replacement enhances cognitive function and musculoskeletal health in postmenopausal women. However, the biological role of testosterone on inflammation and bone metabolism in females is not well understood. Our objective was to measure the impact of androgens and their receptors on periodontal tissues during periodontal repair in female rats. Methods: Seventy female Holtzman rats were divided into seven groups (n = 10/group): negative control; repair control; androgen receptor antagonist (flutamide, 50 mg/kg, every other day); estrogen receptor antagonist (fulvestrant, 1.5 mg/kg/day); testosterone supplementation (durateston, 250 mg/kg, weekly); aromatase inhibitor (anastrozole, 0.2 mg /kg/day); testosterone plus anastrozole. Cotton ligatures were kept for 13 days, when pharmacological treatment was initiated. On day 14, the ligatures were removed. The rats were euthanized on the 17th or the 28th day (n = 5/group/period) for the evaluation of markers related to inflammation and bone. The tissue and serum samples were evaluated using a multiplexed immunoassay for the inflammatory targets. Radiographic and histologic analyses were performed to assess changes in tissues. Results: Blockage of androgen receptors had little effect on inflammatory cell count, although it tended to increase interleukin (IL)-4, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) as well as decrease IL-1, tumor necrosis factor (TNF)-alpha, and IL-6. Flutamide also significantly impaired bone repair (P < 0.05) and had greater osteoclast count, although this last difference was not statistically significant. Testosterone supplementation significantly increased the inflammatory cell count, decreased the levels of IL-4, IL-10, IL-1 beta, IL-6, and TNF-alpha; and increased VEGF and EGF. Conclusion: The blockage of androgen receptors significantly impair bone repair in females through mechanisms that are different from those related to estrogen receptors. (AU)

• FAPESP's process: 13/07833-8 - Participation of androgens on the regulation of immune-inflammatory responses and bone metabolism associated with periodontal health, disease and repair in females
• Grantee: João Paulo Steffens
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/02280-3 - Impact of androgens on the expression of inflammatory cytokines and markers of tissue repair systemically and on periodontal tissues of female rats under conditions of periodontal health, disease and repair
• Grantee: Daniel Olivio Ribeiro
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/23116-4 - Impact of androgens on the inflammatory response, osteoclastogenesis and expression of sex hormones receptors on periodontal tissues of female rats under conditions of periodontal health, disease and repair
• Grantee: Maria Carolina da Costa Albaricci
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/12014-6 - Participation of androgens on the regulation of immune-inflammatory responses and bone metabolism associated with periodontal health, disease and repair in females
• Grantee: Luis Carlos Spolidorio
• Support Opportunities: Regular Research Grants