Stimulation of Steroidogenesis in Immature Rat Leydig Cells Evoked by Interleukin-1α Is Potentiated by Growth Hormone and Insulin-Like Growth Factors

• Published in: Endocrinology (Philadelphia) Vol. 146; no. 1; pp. 221 - 230
• Main Authors: Colón, Eugenia, Svechnikov, Konstantin V, Carlsson-Skwirut, Christine, Bang, Peter, Soder, Olle
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-01-2005; Oxford University Press
• Subjects: Biological and medical sciences; Cell culture; Cooperation; Dihydrotestosterone; Dose-response effects; Fundamental and applied biological sciences. Psychology; Growth factors; Growth hormones; Insulin-like growth factor I; Insulin-like growth factor II; Insulin-like growth factors; Leydig cells; Proteins; Proteolysis; Steroidogenesis; Stimulation; Testosterone; Vertebrates: endocrinology; Rat; Cytokine; Rodentia; Somatotropin hormone; Interleukin 1α; Testicle; Male genital system; Leydig cell; Vertebrata; Insulin like growth factor; Mammalia; Adenohypophyseal hormone; Animal; Steroidogenesis
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2004-0485

The cytokine IL-1α is produced constitutively by the intact testis, but its function in this organ remains largely unknown. In this study we examined cooperation between IL-1α and GH and IGFs with regard to stimulation of steroidogenesis by Leydig cells from 40-d-old rats in vitro. IL-1α alone stimulated testosterone (T) and dihydrotestosterone (DHT) production. GH, IGF-I, or IGF-II alone was without effect on T production, but they were found to elevate DHT release, albeit without an obvious dose-response effect. Costimulation with IL-1α and GH or with IL-1α and IGF-I or IGF-II elevated the rate of steroidogenesis (both T and DHT) above that observed with IL-1α alone. GH was found to increase the level of IGF-I in the cultured Leydig cells, an effect that was potentiated by IL-1α. The costimulatory effect of GH on steroidogenesis was abolished by treatment with picropodophyllin, a specific inhibitor of the IGF-I receptor, indicating that the action of GH is mediated via IGF-I. Moreover, cells costimulated with IL-1α and GH exhibited a marked decrease in the level of intact IGF-binding protein-3 in the culture medium due to the induction of proteolytic activity toward this binding protein. In contrast, secretion of IGF-binding protein-2 was increased by such costimulation. These findings suggest that the stimulation of steroidogenesis in Leydig cells evoked by GH and IGFs requires cooperation with IL-1α. This cooperation may play an important role in connection with postnatal Leydig cell maturation and steroidogenesis.