Influence of growth hormone on the craniofacial complex of transgenic mice

Abstract

Growth hormone (GH) secretion affects bone and cartilage physiology. This study investigated the effect of GH on the size of the craniofacial structures and their angular relationship. Three different models of mice with a genetically altered GH axis were used: GH excess (giant), dwarf GH antagonist (dwarf-Ant), and dwarf GH receptor knockout (dwarf-KO) mice. Each model was compared with the corresponding wild type (Wt). Five craniofacial distances were analysed: craniofacial length, upper face height, mandibular anterior height, mandibular ramus length, and mandibular corpus length. In addition, upper and lower incisor lengths and four angular relationships, nasal bone with cranial base, maxillary plane with cranial base, mandibular plane with cranial base, and the angle of the mandible, were determined. Data were analysed by one-way ANOVA. Craniofacial length, upper face height and mandibular corpus length were significantly increased in the giant mice and significantly reduced in the dwarf mice. Mandibular anterior height and mandibular ramus length were significantly affected in the dwarf-KO mice but not in the giant mice. The length of both the upper and lower incisors was significantly increased and reduced in the giant and dwarf-KO mice, respectively. In addition, the angle of the mandible was significantly increased in the giant mice and significantly reduced in the dwarf mice. It is concluded that GH plays a major role in the growth and development of the craniofacial complex by directly and indirectly modulating the size and the angular relationships of the craniofacial structures, including the incisor teeth.

Growth hormone receptor gene variant and three-dimensional mandibular morphology

“…5,6 Growth hormone (GH), a peptide hormone produced in the anterior pituitary, plays a major role in regulating growth and development of the maxillofacial complex. 7 GH binds growth hormone receptors (GHRs) located on the cell surface in order to activate the intracellular signaling pathways involved in these processes. 8 GH plays an important role in the growth of cartilage, and GHRs are especially present in the mandibular condyle, 9,10 which plays a significant role in the growth and development of craniofacial morphology by regulating the angle and size of the morphology.…”

“…8 GH plays an important role in the growth of cartilage, and GHRs are especially present in the mandibular condyle, 9,10 which plays a significant role in the growth and development of craniofacial morphology by regulating the angle and size of the morphology. 7 Dysfunctional mutations in the GHR gene cause Laron syndrome (GH insensitivity syndrome), which is associated with characteristic craniofacial morphology and short stature. 11 Interestingly, patients with GHR defi-ciency exhibit craniofacial morphology characterized by poor vertical growth.…”

“…However, there are limitations associated with the application of two-dimensional data from lateral cephalograms to the evaluation of craniofacial morphology, which has a complex structure. 7 In the present study, we examined the relationship between three-dimensional mandibular morphology and the rs6184 and rs6180 variants in exon 10 of the GHR gene in a sample of 178 Japanese subjects.…”

Recent Advances in the Genetics of Orthodontics

“…Growth hormone (GH) is a craniofacial morphological determinant; it plays a major role in the growth and development of the craniofacial complex by directly and indirectly modulating the size and the angular relationships of the craniofacial structures (Ramirez-Yanez et al, 2005). Children with deficient or excess GH have been reported to develop unique craniofacial configurations (Pirinen et al, 1994).…”

“…Analysis of the Ghr knockout mouse has revealed that the GH→GHR→insulin-like growth factor 1 system is important in postnatal growth and that GHR plays a role in maintaining proportional skeletal growth (Sjogren et al, 2000). In Ghr knockout mice, the height of the mandibular ramus is significantly reduced (Ramirez-Yanez et al, 2005), and disproportionate skeletal growth is reflected by decreased femur:crown-rump and femur:tibia ratios (Sjogren et al, 2000). There are diverse mutations and polymorphisms in the GHR gene in humans.…”