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Submitted on December 1, 2005
Accepted on June 23, 2006
Discipline of Physiology School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, Australia; Current address: Chancellery, University of South Australia, Adelaide, Australia; Department of Biology, Faculty of Science, Shizuoka University, Ohya 836, Shizuoka 422-8529, Japan
* To whom correspondence should be addressed. E-mail: jeff.schwartz{at}adelaide.edu.au.
The prepartum surge in fetal plasma cortisol is essential for the normal timing of parturition in sheep, and may result from an increase in the ratio of adrenocorticotropic hormone (ACTH) to proopiomelanocortin (POMC) in the fetal circulation. In fetuses subjected to experimental induction of placental restriction, the prepartum surge in fetal cortisol is exaggerated while pituitary POMC mRNA levels are decreased, and in vitro, unstimulated ACTH secretion is elevated in corticotrophs non-responsive to corticotrophin releasing hormone (CRH). We therefore investigated the changes in the relative proportions of cells expressing POMC, ACTH and the CRH receptor, CRHR1, shortly before birth and during chronic placental insufficiency. Placental restriction (PR) was induced by removal of the majority of placental attachment sites in five ewes before mating. Pituitaries were collected from control and PR fetal sheep at 140 d (control n = 4, PR n = 4) and 144 d (control n = 6, PR n = 4). Pituitary sections were labeled with specific antisera raised against POMC, ACTH and CRHR1. Three major subpopulations of corticotrophs were identified which expressed either POMC+ACTH+CRHR1, ACTH+CRHR1 or POMC-only. The proportion of pituitary corticotophs expressing POMC+ACTH+CRHR1 decreased (P < 0.05) between 140d (control 60 ± 1% PR 66 ± 4%) and 144d (control 45 ± 2%, PR 56 ± 6%). A significantly higher (P < 0.05) proportion of corticotrophs expressed POMC+ACTH+CRHR1 in the pituitary of the PR group compared with controls. This study is the first to demonstrate subpopulations of corticotrophs in the fetal sheep pituitary which differentially express POMC, ACTH and CRHR1 and the separate effects of gestational age and placental restriction on these subpopulations of corticotrophs.
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