title: Fetal hypothalamus-pituitary-adrenal responses to estradiol sulfate.
abstract: Estradiol (E(2)) is an important modifier of the activity of the fetal hypothalamus-pituitary-adrenal axis. We have reported that estradiol-3-sulfate (E(2)SO(4)) circulates in fetal blood in far higher concentrations than E(2) and that the fetal brain expresses steroid sulfatase, required for local deconjugation of E(2)SO(4). We performed the present study to test the hypothesis that chronic infusion of E(2)SO(4) chronically increases ACTH and cortisol secretion and that it shortens gestation. Chronically catheterized fetal sheep were treated with E(2)SO(4) intracerebroventricular (n = 5), E(2)SO(4) iv (n = 4), or no steroid infusion (control group, n = 5). Fetuses were subjected to arterial blood sampling every other day until spontaneous birth for plasma hormone analysis. Treatment with E(2)SO(4) attenuated preparturient increases in ACTH secretion near term without affecting the ontogenetic rise in plasma cortisol. Infusion of E(2)SO(4) intracerebroventricularly significantly increased plasma E(2), plasma E(2)SO(4), and plasma progesterone and shortened gestation compared with all other groups. These results are consistent with the conclusion that E(2)SO(4): 1) interacts with the hypothalamus-pituitary-adrenal axis primarily by stimulating cortisol secretion and inhibiting ACTH and pro-ACTH secretion by negative feedback; and 2) stimulates the secretion of E(2) and E(2)SO(4). We conclude that the endocrine response to E(2)SO(4) in the fetus is not identical with the response to E(2).
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Florida 32610-0274, USA. woodc@ufl.edu mail
authors.forename: Charles E
authors.initials: CE
authors.lastname: Wood
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors; D000818:Animals; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005333:Fetus / Q000187:drug effects* / Q000502:physiology; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000196:embryology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000196:embryology; D012756:Sheep
chemical_list: C028628:estradiol-3-sulfate; D004958:Estradiol; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone