The ontogeny of growth hormone sensitivity.
For many years it was believed that the growth hormone (GH) axis does not play a role in growth before birth or during the first year after birth. More recently, however, studies of genetic disorders of growth have led to developments in our understanding of the onset of GH sensitivity and the relationships between the maternal and fetal GH axes. Many children whose GH deficiency (GHD) is diagnosed in late childhood have a good rate of growth in their first year of life. This can be explained when one considers the differences between pituitary and hypothalamic GHD. Many children in whom GHD is diagnosed later in childhood have hypothalamic GHD, which may be masked in the first year of life by a relative lack of somatostatin secretion. Genetic defects in the GH axis lead to a slight degree of growth retardation at birth, consistent with growth impairment in the third trimester only. Conversely, a boy with a deletion in the insulin-like growth factor I (IGF-I) gene showed severe growth retardation at birth, indicating a role for IGF-I during the second and third trimesters. From these results, there are two possible models for the relationship between IGF-I production and other components of the maternal-fetal GH axis: independence of the IGF-I axis from somatotropic influences during the second trimester or, alternatively, redundancy of somatotropic hormones and their receptors. From reports of individuals with naturally occurring mutations that eliminate contributors to the GH axis, redundancy does indeed appear to be a feature of the maternal-fetal GH axis, with GH sensitivity arising around mid-gestation.
Parks
J S
JS
Division of Pediatric Endocrinology, Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga 30322, USA.
D005314:Embryonic and Fetal Development; D005260:Female; D005333:Fetus / Q000502:physiology*; D019382:Human Growth Hormone / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009154:Mutation / Q000502:physiology; D011247:Pregnancy; D011981:Receptors, Prolactin / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000378:metabolism
D011981:Receptors, Prolactin; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone