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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Hypothalamic-pituitary disconnection in fetal sheep blocks the peripartum increases in adrenal responsiveness and adrenal ACTH receptor expression

Departments of ¹Physiology/Pharmacology, ²Obstetrics/Gynecology, and ³Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Submitted 14 January 2005 ; accepted in final form 28 March 2005

Although it has been recognized for over a decade that hypothalamic-pituitary disconnection (HPD) in fetal sheep prevents the late gestation rise in plasma cortisol concentrations, the underlying mechanisms remain unclear. We hypothesized that reductions in adrenal responsiveness and ACTH receptor (ACTH-R) expression may be mediating factors. HPD or sham surgery was performed at 120 days of gestation, and catheters were placed for blood sampling. At 138 days of gestation, fetuses were killed, and adrenals were removed for cell culture and analyses of ACTH-R mRNA and protein. After 48 h, adrenocortical cells were stimulated with ACTH for 2 h, and the medium was collected for cortisol measurement. The same cells were incubated overnight with medium or medium containing ACTH or forskolin (FSK), followed by ACTH stimulation (as above) and cortisol and cellular ACTH-R mRNA analyses. HPD prevented the late gestation increase in plasma cortisol and bioactive ACTH and reduced adrenal ACTH-R mRNA and protein levels by over 35%. HPD cells secreted significantly less cortisol than sham cells (3.2 ± 1.2 vs. 47.3 ± 11.1 ng·ml^–1·2 h^–1) after the initial ACTH stimulation. Overnight incubation of HPD cells with ACTH or FSK restored cortisol responses to acute stimulation to levels seen in sham cells initially. ACTH-R mRNA levels in cells isolated from HPD fetuses were decreased by over 60%, whereas overnight incubation with ACTH or FSK increased levels by approximately twofold. Our findings indicate that the absence of the cortisol surge in HPD fetuses is a consequence, at least in part, of decreased ACTH-R expression and adrenal responsiveness.

ovine fetus; cortisol; dispersed adrenal cells; adrenocorticotropic hormone

This article has been cited by other articles:

				Yixin Su and J. C. Rose The Impact of ACTH Receptor Knockdown on Fetal and Adult Ovine Adrenocortical Cell Function Reproductive Sciences, March 1, 2008; 15(3): 253 - 262. [Abstract] [PDF]

				L. C. Carey, Y. Su, N. K. Valego, and J. C. Rose Infusion of ACTH stimulates expression of adrenal ACTH receptor and steroidogenic acute regulatory protein mRNA in fetal sheep Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E214 - E220. [Abstract] [Full Text] [PDF]