Insulin-like growth factor-I potentiates thyrotropin stimulation of adenylyl cyclase in FRTL-5 cells

Leona Brenner-Gati, Kelly A. Berg, Marvin C. Gershengorn

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

We reported that TSH and insulin-like growth factor-I (IGF-I), which were known to synergistically stimulate DNA synthesis, synergize to elevate the 1,2-diacylglycerol content of FRTL-5 thyroid cells. We presented evidence that cAMP is the proximal mediator of these actions of TSH. To further define the mechanism of this interaction, we investigated the effects of IGF-I on TSH stimulation of adenylyl cyclase. Long and short term effects of IGF-I or high doses of insulin were studied in FRTL-5 cells that were maintained in serum-, hormone-, and growth factor-free medium for 4-7 days (basal cells). When cells were incubated with high doses of insulin for 7 days and acutely stimulated, a 10-fold increase in sensitivity and a 2-fold increase in maximal responsiveness of cAMP accumulation to TSH were observed. To study shorter term effects, cells were preincubated with insulin for 3 h and then exposed to TSH, cholera toxin, or forskolin. Incubation with high doses of insulin for 3 h caused 30-300% increases in cAMP accumulation at high doses of TSH (≥1 mU/ml), cholera toxin (≥0.1 μM), and forskolin, but did not affect the EC50 for TSH. Dose-response studies were consistent with insulin acting via receptors for IGF-I, and IGF-I caused a similar effect. There was a 45% increase in adenylyl cyclase activity stimulated by TSH in membranes isolated from cells incubated with high doses of insulin for 3 h. Pretreatment of FRTL-5 cells with pertussis toxin, which ADP-ribosylates the inhibitory G-protein Gi, or adenosine, which we show inhibits cAMP accumulation by interacting with Gi, did not affect insulin/IGF-I enhancement of cAMP accumulation. We suggest that synergism of actions of TSH and IGF-I may in part be due to IGF-I enhancement of TSH stimulation of adenylyl cyclase.

Original languageEnglish (US)
Pages (from-to)1315-1320
Number of pages6
JournalEndocrinology
Volume125
Issue number3
DOIs
StatePublished - Sep 1989
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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