title: Fetal glucocorticoid synthesis is required for development of fetal adrenal medulla and hypothalamus feedback suppression.
abstract: During pregnancy, fetal glucocorticoid is derived from both maternal supply and fetal secretion. We have created mice with a disruption of the Cyp11a1 gene resulting in loss of fetal steroid secretion but preserving the maternal supply. Cyp11a1null embryos have appreciable although lower amounts of circulating corticosterone, the major mouse glucocorticoid, suggesting that transplacental corticosterone is a major source of corticosterone in fetal circulation. These embryos thus provide a means to examine the effect of fetal glucocorticoids. The adrenal in Cyp11a1 null embryos was disorganized with abnormal mitochondria and oil accumulation. The adrenal medullary cells did not express phenylethanolamine N-methyltransferase and synthesized no epinephrine. Cyp11a1 null embryos had decreased diencephalon Hsd11b1, increased diencephalon Crh, and increased pituitary Pomc expression, leading to higher adrenocorticotropin level in the plasma. These data indicate blunted feedback suppression despite reasonable amounts of circulating corticosterone. Thus, the corticosterone synthesized in situ by the fetus is required for negative feedback suppression of the hypothalamus-pituitary-adrenal axis and for catecholamine synthesis in adrenal medulla.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Chen-Che Jeff
authors.initials: CC
authors.lastname: Huang
authors.forename: Meng-Chun Monica
authors.initials: MC
authors.lastname: Shih
authors.forename: Nai-Chi
authors.initials: NC
authors.lastname: Hsu
authors.forename: Yu
authors.initials: Y
authors.lastname: Chien
authors.forename: Bon-chu
authors.initials: BC
authors.lastname: Chung
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism; D000313:Adrenal Medulla / Q000254:growth & development / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis* / Q000097:blood; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics* / Q000378:metabolism; D003345:Corticosterone / Q000096:biosynthesis* / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D004837:Epinephrine / Q000096:biosynthesis; D025461:Feedback, Physiological / Q000502:physiology*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism; D011247:Pregnancy; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism
chemical_list: D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D002786:Cholesterol Side-Chain Cleavage Enzyme; D010625:Phenylethanolamine N-Methyltransferase; D003345:Corticosterone; D004837:Epinephrine