Insulin-like growth factor-I enhances Luteinizing hormone binding to rat ovarian theca-interstitial cells

• Published in: The Journal of clinical investigation Vol. 86; no. 2; pp. 560 - 565
• Main Authors: CARA, J. F, JIONG FAN, AZZARELLO, J, ROSENFIELD, R. L
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01.08.1990
• Subjects: Androsterone - biosynthesis; Animals; Biological and medical sciences; Cells, Cultured; Cycloheximide - pharmacology; Dichlororibofuranosylbenzimidazole - pharmacology; Dose-Response Relationship, Drug; Female; Fundamental and applied biological sciences. Psychology; Insulin-Like Growth Factor I - pharmacology; Luteinizing Hormone - metabolism; Ovary - metabolism; Protein Biosynthesis - drug effects; Rats; Receptors, LH - metabolism; Somatomedins - pharmacology; Theca Cells - metabolism; Transcription, Genetic - drug effects; Vertebrates: endocrinology; Ovary; Exploration; Steroidogenesis; Hormonal investigation; Animal; Endocrinology
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI114745

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.