Dexamethasone potentiates IGF-I actions in porcine granulosa cells.
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-450scc) mRNA concentrations in porcine granulosa cells. Dexamethasone potentiated IGF-I-stimulated P-450scc mRNA concentrations and progesterone production in granulosa cell cultures. Time-course and dose-response studies showed that maximal enhancement occurred at a 1-microM dexamethasone concentration after 48 h of treatment. This potentiation was prevented by the glucocorticoid receptor antagonist RU-38486, 17 beta-hydroxy-11 beta-[-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.
Urban
R J
RJ
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-1060.
Bodenburg
Y H
YH
Nagamani
M
M
Peirce
J
J
D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D015735:Mifepristone / Q000494:pharmacology; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics; D013552:Swine
D012333:RNA, Messenger; D015735:Mifepristone; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D002786:Cholesterol Side-Chain Cleavage Enzyme; D017526:Receptor, IGF Type 1