The present study was undertaken to identify the mechanisms underlying the effect of insulin-like growth factor I (IGF-I) on FSH receptor (FSHR) in rat granulosa cells. Treatment with FSH produced a substantial increase in FSHR mRNA level, as was expected, while concurrent treatment with increasing concentrations of IGF-I brought about dose-dependent increases in FSH-induced FSHR mRNA, with a maximal response 2.8-fold greater than that induced by FSH alone. IGF-I, either alone or in combination with FSH, did not affect intracellular cAMP levels, whereas it enhanced the effect of 8-bromo (Br)-cAMP on FSHR mRNA production. Taken together, these findings suggest that the ability of IGF-I to enhance FSH action concerning the induction of FSHR is exerted at sites distal to cAMP generation. We then investigated whether the effect of IGF-I and FSH on FSHR mRNA levels was the result of increased transcription and/or altered mRNA stability. The rates of FSHR mRNA gene transcription, assessed by nuclear run-on transcription assay, were not increased by the addition of IGF-I. On the other hand, the decay curves for the 2.4-kilobase (kb) FSHR mRNA transcript in primary granulosa cells significantly altered the slope of the FSHR mRNA decay curve in the presence of IGF-I and increased the half-life of the FSHR mRNA transcript. These data suggest a possible role for changes in FSHR mRNA stability in the IGF-I-induced regulation of FSHR in rat granulosa cells. Treatment with activin produced a substantial increase in FSHR mRNA level, as was expected, and concurrent treatment with IGF-I did not affect activin-induced FSHR mRNA. Our data suggest that the IGF-I effect on FSHR expression is related to cAMP production induced by FSH and may maintain FSHR mRNA level because of prolonged FSHR mRNA stability.