Corticotropin-releasing hormone deficiency reveals major fetal but not adult glucocorticoid need.
The body responds to stress by activation of the hypothalamic-pituitary-adrenal (HPA) axis and release of glucocorticoids. Glucocorticoid production in the adult regulates carbohydrate and amino-acid metabolism, maintains blood pressure, and restrains the inflammatory response. In the fetus, exogenous glucocorticoids accelerate maturation of lung and gastrointestinal enzyme systems and promote hepatic glycogen deposition. Corticotropin-releasing hormone (CRH), a 41-amino-acid neuropeptide produced in the paraventricular nucleus of the hypothalamus and many regions of the cerebral cortex, has been implicated in both the HPA axis and behavioural responses to stress. To define the importance of CRH in the response of the HPA axis to stress and fetal development, we have constructed a mammalian model of CRH deficiency by targeted mutation in embryonic stem (ES) cells. We report here that corticotropin-releasing hormone-deficient mice reveal a fetal glucocorticoid requirement for lung maturation. Postnatally, despite marked glucocorticoid deficiency, these mice exhibit normal growth, fertility and longevity, suggesting that the major role of glucocorticoid is during fetal rather than postnatal life.
Division of Endocrinology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
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L
Muglia
L
L
Jacobson
P
P
Dikkes
J A
JA
Majzoub
D000375:Aging / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000172:deficiency / Q000502:physiology*; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005260:Female; D005938:Glucocorticoids / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000033:anatomy & histology / Q000196:embryology / Q000502:physiology*; D008168:Lung / Q000196:embryology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010913:Pituitary-Adrenal System / Q000033:anatomy & histology / Q000196:embryology / Q000502:physiology*; D013234:Stem Cells
D005938:Glucocorticoids; D003346:Corticotropin-Releasing Hormone