title: Modulation by cortisol of adrenocorticotropin-induced activation of adrenal function in fetal sheep.
abstract: We examined the hypothesis that cortisol (F) modulates the activation of adrenal function induced by treating fetal sheep in vivo with pulsatile ACTH (P-ACTH). Chronically catheterized sheep fetuses were infused in utero for 100 h between day 127 and day 131 of pregnancy with P-ACTH; P-ACTH plus metopirone; P-ACTH plus metopirone plus F; P-ACTH plus metopirone plus dexamethasone, or saline (controls). After 100 h, basal and ACTH-stimulated output of 11-desoxycortisol (S), F, and progesterone from collagenase-dispersed fetal adrenal cells was measured. Adrenal cells from fetuses treated with P-ACTH in vivo had significantly greater basal and stimulated (delta) outputs of F and S in vitro than controls. These effects were attenuated in fetuses pretreated with P-ACTH plus metopirone. Concurrent in vivo treatment with ACTH plus metopirone plus F restored basal and delta outputs of F and S to values that were not significantly different from those after P-ACTH alone. In vivo treatment with dexamethasone in addition to P-ACTH plus metopirone significantly raised basal outputs of F and S, but the cells were unresponsive to ACTH in vitro. Basal output of progesterone was significantly greater after in vivo P-ACTH plus metopirone plus dexamethasone, but no treatment raised delta progesterone output over controls. These results support a role for glucocorticoids in modulating ACTH-induced activation of adrenal function in late gestation fetal sheep.
authors.forename: J R
authors.initials: JR
authors.lastname: Challis
authors.forename: D
authors.initials: D
authors.lastname: Huhtanen
authors.forename: C
authors.initials: C
authors.lastname: Sprague
authors.forename: B F
authors.initials: BF
authors.lastname: Mitchell
authors.forename: S J
authors.initials: SJ
authors.lastname: Lye
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects* / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000502:physiology*; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D009929:Organ Size; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism; D012756:Sheep
chemical_list: D011374:Progesterone; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D006854:Hydrocortisone