Fetal glucocorticoid synthesis is required for development of fetal adrenal medulla and hypothalamus feedback suppression

Chen Che Jeff Huang, Meng Chun Monica Shih, Nai Chi Hsu, Yu Chien, Bon Chu Chung

Research output: Contribution to journalArticle

20 Citations (Scopus)

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. Cyp11a1 null 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.

Original languageEnglish
Pages (from-to)4749-4756
Number of pages8
JournalEndocrinology
Volume153
Issue number10
DOIs
Publication statusPublished - Oct 1 2012

All Science Journal Classification (ASJC) codes

  • Endocrinology

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