Growth hormone (GH) status affects dental development, but how GH influences tooth size/shape is unclear. Since GH affects dental epithelial proliferation, we hypothesized that GH influences the tooth crown and root dimensions. Dentin matrix dimensions were measured in longitudinal sections of decalcified first mandibular molars from 3 genetically modified mice: giant (GH-Excess) mice and dwarf (GH-Antagonist and GH-Receptor-Knockout) mice. GH status was found to influence crown width, root length, and dentin thickness. Analysis of these data suggests that GH influences both tooth crown and root development prior to dentinogenesis as well as during appositional growth of dentin. This is concordant with the expression of paracrine GH and GH receptors during tooth bud morphogenesis, and of GH receptors in the enamel organ, dental papilla, and Hertwig’s epithelial root sheath during dentinogenesis. Based on prior studies, these GH morphogenetic actions may be mediated by the induction of both bone morphogenetic protein and insulin-like growth factor-1 expression.
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References
1.
Chandrashekar V, Bartke A, Coschigano KT, Kopchick JJ (1999). Pituitary and testicular function in growth hormone receptor gene knockout mice. Endocrinology140:1082–1088.
2.
Chen WY, Wight DC, Mehta BV, Wagner TE, Kopchick JJ (1991a). Glycine 119 of bovine growth hormone is critical for growth-promoting activity. Mol Endocrinol5:1845–1852.
3.
Chen WY, White ME, Wagner TE, Kopchick JJ (1991b). Functional antagonism between endogenous mouse growth hormone (GH) and a GH analog results in dwarf transgenic mice. Endocrinology129:1402–1408.
4.
Clayden AM, Young WG, Zhang CZ, Harbrow D, Romanuik K, Waters MJ (1994). Ultrastructure of cementogenesis as affected by growth hormone in the molar periodontium of the hypophysectomized rat. J Periodontal Res29:266–275.
5.
Eckstein F, Lochmuller EM, Koller B, Wehr U, Weusten A, Rambeck W, et al. (2002). Body composition, bone mass and microstructural analysis in GH-transgenic mice reveals that skeletal changes are specific to bone compartment and gender. Growth Horm IGF Res12:116–125.
6.
Gaete M, Lobos N, Torres-Quintana MA (2004). Mouse tooth development time sequence determination for the ICR/Jcl strain. J Oral Sci46:135–141.
7.
Hamori J, Gyulavari O, Szabo B (1974). Tooth size in pituitary dwarfs. J Dent Res53:1302.
8.
Kjellberg H, Beiring M, Albertsson Wikland K (2000). Craniofacial morphology, dental occlusion, tooth eruption, and dental maturity in boys of short stature with or without growth hormone deficiency. Eur J Oral Sci108:359–367.
9.
Knapp JR, Chen WY, Turner ND, Byers FM, Kopchick JJ (1994). Growth patterns and body composition of transgenic mice expressing mutated bovine somatotropin genes. J Anim Sci72:2812–2819.
10.
Kopchick JJ, Bellush LL, Coschigano KT (1999). Transgenic models of growth hormone action. Annu Rev Nutr19:437–461.
11.
Levin HL (1965). Some dental aspects of endocrine diseases. Oral Surg Oral Med Oral Pathol19:466–477.
12.
Li H, Bartold PM, Young WG, Xiao Y, Waters MJ (2001). Growth hormone induces bone morphogenetic proteins and bone-related proteins in the developing rat periodontium. J Bone Miner Res16:1068–1076.
13.
Lisi S, Peterkova R, Peterka M, Vonesch JL, Ruch JV, Lesot H (2003). Tooth morphogenesis and pattern of odontoblast differentiation. Connect Tissue Res44(Suppl 1):167–170.
14.
Lupu F, Terwilliger JD, Lee K, Segre GV, Efstratiadis A (2001). Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth. Dev Biol229:141–162.
15.
Peterka M, Lesot H, Peterkova R (2002). Body weight in mouse embryos specifies staging of tooth development. Connect Tissue Res43:186–190.
16.
Sarnat H, Kaplan I, Pertzelan A, Laron Z (1988). Comparison of dental findings in patients with isolated growth hormone deficiency treated with human growth hormone (hGH) and in untreated patients with Laron-type dwarfism. Oral Surg Oral Med Oral Pathol66:581–586.
17.
Seuntjens E, Hauspie A, Vankelecom H, Denef C (2002). Ontogeny of plurihormonal cells in the anterior pituitary of the mouse, as studied by means of hormone mRNA detection in single cells. J Neuroendocrinol14:611–619.
18.
Slabaugh MB, Lieberman ME, Rutledge JJ, Gorski J (1982). Ontogeny of growth hormone and prolactin gene expression in mice. Endocrinology110:1489–1497.
19.
Smid JR, Rowland JE, Young WG, Daley TJ, Coschigano KT, Kopchick JJ, et al. (2004). Mouse cellular cementum is highly dependent on growth hormone status. J Dent Res83:35–39.
20.
Tabata MJ, Fujii T, Liu JG, Ohmori T, Abe M, Wakisaka S, et al. (2002). Bone morphogenetic protein 4 is involved in cusp formation in molar tooth germ of mice. Eur J Oral Sci110:114–120.
21.
Thesleff I, Keranen S, Jernvall J (2001). Enamel knots as signaling centers linking tooth morphogenesis and odontoblast differentiation. Adv Dent Res15:14–18.
22.
Turner ND, Knapp JR, Byers FM, Kopchick JJ (2001). Physical and mechanical characteristics of tibias from transgenic mice expressing mutant bovine growth hormone genes. Exp Biol Med (Maywood)226:133–139.
23.
Wang J, Zhou J, Cheng CM, Kopchick JJ, Bondy CA (2004). Evidence supporting dual, IGF-I-independent and IGF-I-dependent, roles for GH in promoting longitudinal bone growth. J Endocrinol180:247–255.
24.
Young WG (1995). Growth hormone and insulin-like growth factor-I in odontogenesis. Int J Dev Biol39:263–272.
25.
Young WG, Zhang CZ, Li H, Osborne P, Waters MJ (1992). The influence of growth hormone on cell proliferation in odontogenic epithelia by bromodeoxyuridine immunocytochemistry and morphometry in the Lewis dwarf rat. J Dent Res71:1807–1811.
26.
Young WG, Ruch JV, Stevens MR, Bègue-Kirn C, Zhang CZ, Lesot H, et al. (1995). Comparison of the effects of growth hormone, insulin-like growth factor-I and fetal calf serum on mouse molar odontogenesis in vitro. Arch Oral Biol40:789–799.
27.
Young WG, Li H, Xiao Y, Waters MJ, Bartold PM (2001). Growth-hormone-stimulated dentinogenesis in Lewis dwarf rat molars. J Dent Res80:1742–1747.
28.
Zhang CZ, Young WG, Li H, Clayden AM, Garcia-Aragon J, Waters MJ (1992). Expression of growth hormone receptor by immunocytochemistry in rat molar root formation and alveolar bone remodeling. Calcif Tissue Int50:541–546.
29.
Zhang CZ, Young WG, Breipohl W, Doehrn S, Li H, Waters MJ (1994). Growth hormone regulates an N-acetylgalactosamine component in odontogenesis: a specific lectin-binding study in the Lewis dwarf rat. J Oral Pathol Med23:193–199.
30.
Zhang CZ, Li H, Young WG, Bartold PM, Chen C, Waters MJ (1997). Evidence for a local action of growth hormone in embryonic tooth development in the rat. Growth Factors14:131–143.
31.
Zhou Y, Xu BC, Maheshwari HG, He L, Reed M, Lozykowski M, et al. (1997). A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse). Proc Natl Acad Sci USA94:13215–13220.
