Table 1.
Studies reporting effects and interactions of SSH and periodontium.
| Progestagens | Androgens | Estrogens | |
|---|---|---|---|
| Gingiva | |||
| Receptors | PR in hGF (35). | DHT receptors in the cytoplasm of gingival tissue (22) and AR in gingival tissue (36) and gingival fibroblasts (24, 37). | Expression of ER (23) and ERβ on gingival epithelial cells (38, 39). |
| Metabolism | Metabolism of progesterone by 5α-reductase, 3β-hydroxysteroid-dehydrogenase, and 20α-hydroxysteroid-dehydrogenase (40). Metabolism of progesterone with varied by-products as a result (41). Progesterone modulates androgen metabolism in hGF (42, 43). |
Conversion of androstenedione to testosterone by 17β-hydroxy-C19-steroid oxidoreductase (44). Metabolism of testosterone and androstenedione into reduced forms in hGF (42, 43) and in male and female gingival tissue (45). Identification of different testosterone-reducing enzymes in gingiva (46). |
Conversion of estrone to estradiol by 17β-hydroxy-C18-steroid oxidoreductase (47). Estradiol modulates androgen metabolism in hGF (42, 43). |
| Cellular growth, differentiation, proliferation and migration | Testosterone stimulates proliferation of hGF (36). | Estrogen induces proliferation of hGF (48). Estrogen levels correlate to the expression of cytokeratin 5 (49). |
|
| Cytokine production and inflammation markers | Progesterone inhibits (Gornstein et al., 1999; Lapp et al., 1995) or enhances (Yokoyama et al., 2005) IL-6 production in hGF. Progesterone enhances IL-8 and VEGF production (50). Progesterone upregulates the expression of COX-2 in hGF (51). |
IL-6 expression in oral fibroblasts is inhibited by testosterone (36, 37, 52) and DHT (37, 52). Testosterone downregulates the expression of IL-17 after 24 hours of exposure (53). Testosterone inhibits prostaglandin formation (54). |
Production of vascular endothelial growth factor (VEGF), interleukin IL-6 and IL-8 by hGF increased following stimulation with estradiol (50). The pro-inflammatory effects on hPDL cells induced by LPS (secretion of TNF-alpha, IL-1beta, IL-6, and receptor activator of NF- B ligand (RANKL)) are reversed by Estradiol. Also, estradiol upregulates osteoprotegerin expression, thus attenuating the osteoprotegerin vs. RANKL ratio (55). 17β-estradiol upregulates the expression of COX-2 in hGF (51). |
| PDL | |||
| Receptors | Ability of hPDLCs to bind progestins, suggesting the presence of PR (56) and expression of PR (57) | AR in periodontal tissue and hPDL fibroblasts (24, 37, 53). | Expression of estradiol (56) and estrogen receptors (53, 58), expression of ERβ in the nuclei (59) and mitochondria of hPDLCs (60) and expression of only ERα (61), ERβ (62) or both ERα and ERβ in hPDLCs (63, 64). hPDLSCs express ERα and ERβ (65, 66). Upregulation of ERβ during osteogenesis (63). |
| Metabolism | Metabolism of testosterone and androstenedione (67). | Collagen and DNA synthesis of hPDLCs is not influenced by estradiol (68) | |
| Cellular growth, differentiation, proliferation and migration | Progesterone stimulates hPDLCs proliferation and differentiation under osteogenic conditions. Also, progesterone can enhance alkaline phosphatase activity and the expression of genes coding for mineralization processes (57). | Estrogen downregulates osteoclast formation (69), enhances osteocalcin production (70, 71), alkaline phosphatase activity (70) and mineralized nodule formation of hPDLCs (72). Estrogen also induces osteogenic differentiation of hPDLSCs via ERα (65) and ERβ (66). Estradiol inhibits the growth rate of hPDLCs in a dose dependent manner (56), increases their proliferation (62, 73) and enhances osteogenic differentiation (62, 64, 73). Estradiol also increases expression of osteoprotegerin (OPG) and decreases expression of nuclear factor-kappa β ligand (RANKL) in hPDLCs via ERβ (61). PDLSCs, when supplemented with estradiol, show odonto/osteoblast differentiation capacities (74) |
|
| Cementum | |||
| Expression of ERα and ERβ (75). 17- β Estradiol significantly increases proliferation of hCDCs (76). |
|||
| Alveolar bone | |||
| See Cellular growth, differentiation, proliferation and migration of PDL for overlap between hPDLCs and alveolar bone on: differentiation, alkaline phosphatase activity and expression of genes related to the mineralization process. | See Cellular growth, differentiation, proliferation and migration of PDL for overlap between hPDLCs and alveolar bone on: osteogenic differentiation, osteoclast formation. Osteocalcin production, alkaline phosphatase activity, mineralized nodule formation, upregulation of OPG and down-regulation of RANKL. | ||
AR, androgen receptor; DHT, 5α-Dihydrotestosterone; ER, estrogen receptor; hGF, human gingival fibroblasts; hPDL, human periodontal ligament; hPDLCs, human periodontal ligament cells; hPDLSCs, human periodontal ligament stem cells; hCDCs, human cementum-derived cells; OPG, osteoprotegerin; PDL, periodontal ligament; PR, progesterone receptor; RANKL, nuclear factor-kappa β ligand; VEGF, vascular endothelial growth factor.