Dexamethasone potentiates IGF-I actions in porcine granulosa cells

R. J. Urban, Y. H. Bodenburg, M. Nagamani, J. Peirce

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

To understand better interactions between glucocorticoids and insulin- like growth factor I (IGF-I) in the ovary, we studied the effects of dexamethasone on IGF-I stimulation of P-450 cholesterol side-chain cleavage enzyme (P-450(scc)) mRNA concentrations to porcine granulosa cells. Dexamethasone potentiated IGF-I-stimulated P-450(scc) mRNA concentrations and progesterone production in granulosa cell cultures. Time-course and dose- response studies showed that maximal enhancement occurred at a 1-μM dexamethasone concentration after 48 h of treatment. This potentiation was prevented by the glucocorticoid receptor antagonist RU-38486, 17β-hydroxy- 11β-[-4-dimethyl-aminophenyl]estra-4,9,-dien-3-one (RU-486). We investigated mechanisms for this potentiation by performing IGF-I binding studies in porcine granulosa cells. Dexamethasone increased IGF-I binding, and Scatchard analysis showed this enhanced binding was caused by an increase in receptor concentration. Northern blot hybridization using a rat type I IGF-I receptor gene riboprobe showed that although dexamethasone alone did not increase IGF- I receptor mRNA concentrations, it did prevent a decrease in receptor mRNA concentrations caused by IGF-I. In addition, we used synthetic primers from conserved regions of the rat type I IGF-I receptor gene with total RNA from porcine granulosa cells and polymerase chain reaction to isolate a 615-base pair porcine type I IGF-I receptor cDNA clone. Ribonuclease protection assay results were similar to those found with the rat IGF-I receptor riboprobe. We conclude that dexamethasone potentiates IGF-I actions on steroidogenesis in the porcine ovary. Possible mechanisms for this potentiation include the ability of dexamethasone to enhance IGF-I binding to porcine granulosa cells and prevent decreases in type I IGF-I receptor mRNA concentrations caused by IGF-I.

Original languageEnglish (US)
Pages (from-to)E115-E123
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume267
Issue number1 30-1
DOIs
StatePublished - 1994

Keywords

  • P-450(scc)
  • RU-486
  • steroidogenesis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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