Promotional role for glucocorticoids in the development of intracellular signalling: enhanced cardiac and renal adenylate cyclase reactivity to beta-adrenergic and non-adrenergic stimuli after low-dose fetal dexamethasone exposure.
Journal Article (Journal Article)
Fetal exposure to high doses of glucocorticoids, as used to aid lung maturation in the therapy of Respiratory Distress Syndrome, causes growth retardation and interference with development of beta-adrenergic receptor-mediated cell signalling. The current study examined whether lower levels of steroids might instead play a positive trophic role in receptor transduction. Pregnant rats were given dexamethasone at or below the threshold for growth impairment (0.05-0.2 mg/kg) on gestational days 17, 18 and 19, and the beta-receptor-mediated stimulation of adenylate cyclase activity was evaluated in membrane preparations from heart and kidney. The enzymatic response to isoproterenol was compared with effects on: (1) basal (unstimulated) adenylate cyclase, (2) adenylate cyclase stimulation mediated by forskolin, which bypasses the beta-receptor, and (3) development of beta-receptor binding capabilities, assessed with [125I]pindolol. In the heart, prenatal exposure to dexamethasone produced a dose-dependent enhancement of beta-receptor-mediated stimulation of adenylate cyclase activity; however, both basal and forskolin-stimulated activity were also increased and beta-receptor binding was relatively unaffected. These results suggest that enhanced responsiveness was occurring at the level of the cyclase itself, rather than by effects on receptors or their G-protein coupling to enzyme activity. Promotional effects on adenylate cyclase were detectable at the low dose of dexamethasone, without any evidence of growth impairment. Furthermore, the effects displayed selectivity for age and tissue: adults treated with dexamethasone did not show the effect, and the heart was more sensitively affected than was the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
Full Text
Duke Authors
Cited Authors
- Bian, XP; Seidler, FJ; Slotkin, TA
Published Date
- December 1991
Published In
Volume / Issue
- 16 / 6
Start / End Page
- 331 - 339
PubMed ID
- 1668597
International Standard Serial Number (ISSN)
- 0141-9846
Language
- eng
Conference Location
- England