| First Author | Frohman LA | Year | 1996 |
| Journal | J Pediatr Endocrinol Metab | Volume | 9 Suppl 3 |
| Pages | 233-6 | PubMed ID | 8887166 |
| Mgi Jnum | J:35587 | Mgi Id | MGI:83033 |
| Citation | Frohman LA (1996) Growth hormone physiology in health and disease: insights using genetic and transgenic models. J Pediatr Endocrinol Metab 9 Suppl 3:233-6 |
| abstractText | Growth hormone (GH) secretion is controlled by a complex neuroendocrine mechanism mediated by two hypothalamic hormones, GH-releasing hormone (GHRH) and somatostatin (SRIH). Their regulation, in turn, involves signals originating within both the central nervous system and the periphery. Among the peripheral agents, GH and IGF-I exhibit important feedback effects at hypothalamic and pituitary levels. During the past decade, the mechanisms of action of GHRH and SRM at the pituitary level have been extensively studied and clarified. Both hormones exert their effects by binding to G-protein-coupled receptors on the somatotrope cell membrane. Quantitatively, the most important signal transduction pathway involves activation of adenylyl cyclase and protein kinase A. The eventual cascade of effects alters GH release, and in the case of GHRH, affects GH synthesis and somatotrope mitogenesis. Despite these advances in our understanding of GH secretion, the pathogenesis of the most commonly observed growth disorder of GH secretion, idiopathic GH deficiency (IGHD), remains elusive. This disorder, which affects primarily children, is characterized by decreased GH secretion, a lack of structural abnormalities of the hypothalamus or pituitary (as determined by imaging studies) and a variable GH secretory response to GHRH. The response is essentially normal in some patients while in others it is markedly reduced or absent. In some of the latter groups, repeated stimulation with GHRH enhances the GH response, while in others priming is ineffective. Similarly, the responses to therapy using GHRH are also variable, with only about half of treated children exhibiting an adequate growth response. These findings suggest that IGHD may represent a common phenotype that has multiple etiologies. In an attempt to gain further insight into possible mechanisms of pathogenesis, we have characterized three unique animal models of GH deficiency- mediated dwarfism. Two are genetic disorders (the 'little'' mouse and the ''dwarf'' rat) and the third is a transgenic model (the tyrosine hydroxylase-human GH mouse). |
