Regulation of testicular function by insulin and transforming growth factor-beta.
Hyperinsulinism is associated with disorders of androgen production in humans. We have studied the effects of insulin and insulin-like growth factor-1 on androgen production in vitro using a crude preparation of mouse Leydig cells incubated with luteinizing hormone in a serum-free medium. We found a positive correlation between testosterone production and the luteinizing hormone dose over 3 hours. Exposure of the cells for 1 hour to insulin (1 micrograms/ml) prior to the addition of luteinizing hormone significantly augmented the amount of testosterone produced in response to the gonadotropin when added after this preincubation. In contrast, prior exposure of the cells to proinsulin (30 micrograms/ml), insulin-like growth factor-1 (30 ng/ml), or epidermal growth factor-1 (1 micrograms/ml) did not influence the testosterone response to luteinizing hormone. Transforming growth factor-beta reduced the testosterone response to luteinizing hormone. Transforming growth factor-beta (1,000 pg/ml) blocked the insulin augmentation of luteinizing hormone-stimulated testosterone production. We conclude that insulin has an endocrine effect on testosterone production by mouse Leydig cells in vitro. Furthermore, the Leydig cell response to insulin is itself sensitive to interaction with transforming growth factor-beta which may operate as part of the paracrine control of Leydig cell function.
Endocrine Unit, University College and Middlesex School of Medicine, Middlesex Hospital, London, UK.
W M
WM
Bebakar
J W
JW
Honour
D
D
Foster
Y L
YL
Liu
H S
HS
Jacobs
D000375:Aging; D000818:Animals; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D051379:Mice; D011384:Proinsulin / Q000494:pharmacology; D013739:Testosterone / Q000096:biosynthesis*; D015291:Transforming Growth Factors / Q000494:pharmacology*
D007328:Insulin; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D015291:Transforming Growth Factors; D007986:Luteinizing Hormone; D011384:Proinsulin