A role of insulin-like growth factor I for follicle-stimulating hormone receptor expression in rat granulosa cells.
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.
Minegishi
T
T
Department of Obstetrics and Gynecology, School of Medicine, Gunma University, Maebashi, Gunma 371-8511, Japan. tminegis@sb.gunma-u.ac.jp
Hirakawa
T
T
Kishi
H
H
Abe
K
K
Abe
Y
Y
Mizutani
T
T
Miyamoto
K
K
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D028341:Activins; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D005246:Feedback / Q000502:physiology; D005260:Female; D005822:Genetic Vectors; D006107:Granulosa Cells / Q000378:metabolism*; D007265:Inhibins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000502:physiology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D011962:Receptors, FSH / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology; D014162:Transfection / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology
D012333:RNA, Messenger; D011962:Receptors, FSH; D028341:Activins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D007265:Inhibins; D007334:Insulin-Like Growth Factor I