title: Adrenocortical sensitivity to ACTH in neonatal rats: correlation of corticosterone responses and adrenal cAMP content.
abstract: A coordinated hypothalamic-pituitary-adrenal axis response is important for the survival of newborns during stress. We have previously shown that prior to postnatal day (PD) 5, neonatal rats exposed to hypoxia (one of the most common stressors effecting premature neonates) exhibit a large corticosterone response with a minimal increase in immunoassayable plasma ACTH and without a detectable increase in adrenal cAMP content (the critical second messenger). To explore the phenomenon of ACTH-stimulated steroidogenesis in the neonate, we investigated the adrenal response to exogenous ACTH in the normoxic neonatal rat. Rat pups at PD2 and PD8 were injected intraperitoneally with porcine ACTH at low, moderate, or high doses (1, 4, or 20 μg/kg body wt). Trunk blood and whole adrenal glands were collected at baseline (before injection) and 15, 30, or 60 min after the injection. ACTH stimulated corticosterone release in PD2 and PD8 pups. In PD2 pups, plasma corticosterone at baseline and during the response to ACTH injection was greater than values measured in PD8 pups, despite lower adrenal cAMP content in PD2 pups. Specifically, the low and moderate physiological ACTH doses produced a large corticosterone response in PD2 pups without a change in adrenal cAMP content. At extremely high, pharmacological levels of plasma ACTH in PD2 pups (exceeding 3,000 pg/ml), an increase in adrenal cAMP was measured. We conclude that physiological increases in plasma ACTH may stimulate adrenal steroidogenesis in PD2 pups through a non-cAMP-mediated pathway.
authors.affiliation: Endocrine Research Laboratory; Aurora St. Luke's Medical Center, Aurora Research Institute, Milwaukee, Wisconsin; and Departments of Medicine, Surgery, and Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bodager
authors.affiliation: Endocrine Research Laboratory; Aurora St. Luke's Medical Center, Aurora Research Institute, Milwaukee, Wisconsin; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gessert
authors.affiliation: Endocrine Research Laboratory; Aurora St. Luke's Medical Center, Aurora Research Institute, Milwaukee, Wisconsin; and.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Bruder
authors.affiliation: Endocrine Research Laboratory; Aurora St. Luke's Medical Center, Aurora Research Institute, Milwaukee, Wisconsin; and.
authors.forename: Ashley
authors.initials: A
authors.lastname: Gehrand
authors.affiliation: Endocrine Research Laboratory; Aurora St. Luke's Medical Center, Aurora Research Institute, Milwaukee, Wisconsin; and Departments of Medicine, Surgery, and Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin hraff@mcw.edu.
authors.forename: Hershel
authors.initials: H
authors.lastname: Raff
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D003345:Corticosterone / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D023421:Models, Animal; D010913:Pituitary-Adrenal System / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D003345:Corticosterone
keywords: adrenal gland; corticosterone; newborn; synthetic ACTH(1–39), second messenger