Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/8146
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Type: Journal article
Title: Metyrapone infusion stimulates adrenal growth without activating the cell cycle or the IGF system in the late gestation fetal sheep
Author: Warnes, K.
McMillen, I.
Robinson, J.
Coulter, C.
Citation: Endocrine Research, 2004; 30(4):535-539
Publisher: Marcel Dekker Inc
Issue Date: 2004
ISSN: 0743-5800
1532-4206
Statement of
Responsibility: 
K. E. Warnes, I. C. McMillen, J. S. Robinson, Catherine L. Coulter
Abstract: Recently, we have demonstrated that administration of metyrapone, to suppress cortisol synthesis and decrease negative feedback at the pituitary, results in an increase in circulating ACTH and adrenal growth in the late gestation sheep fetus. In these studies, we demonstrated a 2-fold increase in adrenocortical growth using morphometric techniques. To elucidate the potential molecular mechanisms leading to the increase in adrenal growth, we examined adrenal expression of the cell cycle regulatory proteins (cyclin D1) and cyclin-kinase inhibitory proteins (p16ink, p21Cip), and insulin-like growth factor-II (IGF-II), IGF-binding protein 2 (IGFBP-2) and IGF-I type 1 Receptor (IGF1R) from fetuses infused with metyrapone or vehicle for 15 days. There was a significant decrease in adrenal expression of cyclin D1 in metyrapone- (472.0 ± 29.7) compared with vehicle-infused (662.7 ± 29.2) fetuses. There was no significant difference, however, in the adrenal expression of the cyclin-kinase inhibitory proteins (p16ink or p21Cip) or in the IGF system (IGF-II, IGFBP-2 or IGF1R) mRNA between metyrapone- and vehicle-infused. In summary, in this model of metyrapone-activated adrenal cortical hypertrophy, growth occurs with a suppression of the rate-limiting cell cycle protein and without activation of the IGF system.
Keywords: Fetal adrenal; Adrenal growth; Metyrapone
Description: © 2008 Informa plc
RMID: 0020041648
DOI: 10.1081/ERC-200043619
Published version: http://www.informaworld.com/smpp/content?content=10.1081/ERC-200043619
Appears in Collections:Obstetrics and Gynaecology publications

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