title: A specific CRH antagonist attenuates ACTH-stimulated cortisol secretion in ovine adrenocortical cells.
abstract: Corticotropin releasing hormone (CRH) has been detected in the adrenal gland of many species and may be involved in regulation of glucocorticoid secretion. In cultured human fetal adrenal definitive/transitional zone cells, CRH upregulates the adrenocorticotropic hormone (ACTH) receptor and steroidogenic enzymes and is blocked by the selective CRH type 1 receptor (CRH(1)) antagonist, antalarmin. Based on these findings and evidence that antalarmin infusion into sheep suppressed prepartum increases in cortisol, we hypothesized that antalarmin would influence adrenal cortisol secretion. Antalarmin strongly attenuated ACTH and forskolin (FSK)-stimulated cortisol and cyclic adenosine monophosphate (cAMP) release from cultured ovine adrenocortical cells but did not prevent ACTH binding to cells or ACTH-induced proliferation in adult cells. Corticotropin releasing hormone was minimally effective as a secretagogue but increased the cortisol response to subsequent ACTH. These results suggest that antalarmin attenuates ACTH-induced cortisol secretion from cultured ovine adrenal cortical cells at a site distal to the ACTH receptor. Although CRH may modulate the secretory response to ACTH, it is probably not a direct cortisol secretagogue in the sheep.
authors.affiliation: Center of Research for Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. nvalego@wfubmc.edu
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Valego
authors.forename: James C
authors.initials: JC
authors.lastname: Rose
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006854:Hydrocortisone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D011247:Pregnancy; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012756:Sheep
chemical_list: D010446:Peptide Fragments; D011743:Pyrimidines; D011758:Pyrroles; C103016:antalarmin; C104416:astressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone