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Subpopulations of Corticotrophs in the Sheep Pituitary during Late Gestation: Effects of Development and Placental Restriction

Discipline of Physiology School of Molecular and Biomedical Sciences (K.F., I.C.M., J.S.), University of Adelaide, Adelaide, Australia; and Department of Biology (S.T.), Faculty of Science, Shizuoka University, Ohya 836, Shizuoka 422-8529, Japan

Address all correspondence and requests for reprints to: Jeffrey Schwartz, Discipline of Physiology, School of Molecular and Biomedical Sciences, University of Adelaide, North Terrace, Adelaide 5005, Australia. 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 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, whereas pituitary POMC mRNA levels are decreased, and in vitro, unstimulated ACTH secretion is elevated in corticotrophs nonresponsive to CRH. We therefore investigated the changes in the relative proportions of cells expressing POMC, ACTH, and the CRH type 1 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 that expressed POMC + ACTH + CRHR₁, ACTH + CRHR₁, or POMC only. The proportion of pituitary corticotrophs expressing POMC + ACTH + CRHR₁ decreased (P < 0.05) between 140 (control, 60 ± 1%; PR, 66 ± 4%) and 144 (control, 45 ± 2%; PR, 56 ± 6%) d. 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 that 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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