Urocortin: a mechanism for the sustained activation of the HPA axis in the late-gestation ovine fetus?
We hypothesized that urocortin might be produced in the pituitary of the late-gestation ovine fetus in a manner that could contribute to the regulation of ACTH output. We used in situ hybridization and immunohistochemistry to identify urocortin mRNA and protein in late-gestation fetal pituitary tissue. Levels of urocortin mRNA rose during late gestation and were associated temporally with rising concentrations of pituitary proopiomelanocortin (POMC) mRNA. Urocortin was localized both to cells expressing ACTH and to non-ACTH cells by use of dual immunofluorescence histochemistry. Transfection of pituitary cultures with urocortin antisense probe reduced ACTH output, whereas added urocortin stimulated ACTH output from cultured pituitary cells. Cortisol infusion for 96 h in chronically catheterized late-gestation fetal sheep significantly stimulated levels of pituitary urocortin mRNA. We conclude that urocortin is expressed in the ovine fetal pituitary and localizes with, and can stimulate output of, ACTH. Regulation of urocortin by cortisol suggests a mechanism to override negative feedback and sustain feedforward of fetal hypothalamic-pituitary-adrenal function, leading to birth.
Holloway
Alison C
AC
Department of Physiology, Canadian Institute for Health Research Groups in Fetal and Neonatal Health and Development, University of Toronto, Toronto, Ontario M55 1A8, Canada. hollow@mcmaster.ca
Howe
David C
DC
Chan
Gabriel
G
Clifton
Vicki L
VL
Smith
Roger
R
Challis
John R G
JR
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D019898:Autocrine Communication / Q000502:physiology; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D004333:Drug Administration Routes; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D006854:Hydrocortisone / Q000008:administration & dosage / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000196:embryology / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019899:Paracrine Communication / Q000502:physiology; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000196:embryology / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012756:Sheep; D054832:Urocortins
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D054832:Urocortins; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone