Regulation of androgen production in cultured human thecal cells by insulin-like growth factor I and insulin.

ABSTRACT

OBJECTIVES: To investigate if human thecal cells contain messenger ribonucleic acid (RNA) encoding insulin-like growth factor I (IGF-I) and insulin receptors and if IGF-I and insulin could stimulate androgen production in thecal cells. DESIGN: Poly-adenine+ RNA was extracted from fresh thecal tissue, and the expression of the genes encoding insulin and IGF-I receptors were analyzed. Isolated thecal cells were cultured 4 to 6 days with and without hormones. SETTING: Procedures were performed in a university laboratory. PATIENTS Eight women in the follicular phase of natural cycles were undergoing gynecological laparotomy for reasons unrelated to ovarian pathology. The leading follicle(s) was excised, and dispersed cells of the theca interna layer were isolated through combined mechanical and enzymatic techniques. INTERVENTIONS: Luteinizing hormone (LH), IGF-I, and insulin were added to the cell cultures. MAIN OUTCOME MEASURE: The expression of IGF-I receptor and insulin receptor transcripts were analyzed by Northern blot. Medium levels of androstenedione and testosterone were measured by radioimmunoassay. RESULTS: In the separated thecal tissue both IGF-I receptor and insulin-receptor transcripts were detected. Insulin-like growth factor I and insulin potentiated LH-induced androgen secretion while having less pronounced effects on basal androgen production. CONCLUSION: The present study demonstrates that both insulin and IGF-I receptor genes are expressed and that insulin and IGF-I can stimulate steroid production in human thecal cells. The study provides further support for the hypothesis that IGF-I and insulin may be involved both in physiological regulation of ovarian function as well as in its pathophysiology.