Insulin-like growth factor-I enhances luteinizing hormone binding to rat ovarian theca-interstitial cells.
We tested the hypothesis that insulin-like growth factor-I (IGF-I) stimulates ovarian androgen production by increasing theca-interstitial cell luteinizing hormone (LH) binding affinity and/or binding capacity. We then investigated the role of transcriptional and translational events in mediating these actions of IGF-I. LH bound to saturable, high affinity binding sites on rat ovarian theca-interstitial cells. Preincubation with LH produced a decrease in LH binding capacity with no effect on LH binding affinity. Treatment with IGF-I, both in the absence and presence of LH, increased LH binding capacity 1.5- to 2-fold with no change in LH binding affinity. Androgen production was increased progressively by LH, suggesting that LH-stimulated steroidogenesis is not tightly coupled to LH receptor downregulation. IGF-I increased androgen synthesis in proportion to its upregulation of LH binding capacity. Transcriptional inhibition with dichlorobenzimidazole riboside inhibited the IGF-I-mediated increase in LH binding capacity but had no effect on androgen production. Translational inhibition with cycloheximide inhibited both the IGF-I-mediated increase in LH binding and stimulation of androgen synthesis. We conclude that IGF-I increases theca-interstitial cell LH binding capacity and reverses the LH-induced downregulation of LH binding sites. The enhancement of LH binding by IGF-I is compatible with transcriptional mediation whereas the effect of IGF-I on androgen synthesis appears to be mediated by a direct effect of the peptide on the translational process(es) involved in steroidogenesis.
Cara
J F
JF
Department of Pediatrics, University of Chicago Pritzker School of Medicine, Illinois.
Fan
J
J
Azzarello
J
J
Rosenfield
R L
RL
D000738:Androsterone / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D011974:Receptors, LH / Q000378:metabolism*; D013002:Somatomedins / Q000494:pharmacology*; D013799:Theca Cells / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D011974:Receptors, LH; D013002:Somatomedins; D004004:Dichlororibofuranosylbenzimidazole; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D003513:Cycloheximide; D000738:Androsterone