Glucocorticoids regulate the development of intracellular signaling: enhanced forebrain adenylate cyclase catalytic subunit activity after fetal dexamethasone exposure.

Journal Article (Journal Article)

Although glucocorticoids cause growth retardation and interfere with cell development, selective promotion of some aspects of cell function also has been reported. The current study examines whether glucocorticoids enhance intracellular transduction mechanisms mediated by adenylate cyclase in the developing forebrain, a region in which steroids have been shown to interfere with cell replication, maturation, and growth. Pregnant rats were given dexamethasone at doses spanning the threshold for growth impairment (0.05, 0.2, and 0.8 mg/kg) on gestational days 17, 18, and 19, and development of adenylate cyclase was evaluated in membrane preparations, using four different activity measures; basal adenylate cyclase in the absence or presence of GTP, maximal G-protein activation by fluoride in the presence of GTP, and stimulation mediated by forskolin-Mn2+, which bypasses the G-proteins. Prenatal exposure to dexamethasone produced a dose-dependent impairment of body growth, with smaller deficits in forebrain weights (brain sparing) indicative of systemic toxicity. Basal adenylate cyclase activity was unaffected by dexamethasone treatment, regardless of whether GTP was present in the assay. Similarly, fluoride stimulation developed normally in all dexamethasone groups. However, forskolin-Mn(2+)-stimulated activity was significantly enhanced in a dose-dependent fashion. These results suggest that glucocorticoids serve as positive factors for the development of adenylate cyclase catalytic subunit activity, independently of their adverse effects on general growth and development; thus, these hormones may be a primary regulator of cell signaling during early development.

Full Text

Duke Authors

Cited Authors

  • Slotkin, TA; McCook, EC; Seidler, FJ

Published Date

  • 1993

Published In

Volume / Issue

  • 32 / 4

Start / End Page

  • 359 - 364

PubMed ID

  • 8221125

International Standard Serial Number (ISSN)

  • 0361-9230

Digital Object Identifier (DOI)

  • 10.1016/0361-9230(93)90200-u


  • eng

Conference Location

  • United States