Abstract
Effects of insulin-like growth factor I on steroidogenic enzyme expression levels in mouse Leydig cells
Wang,Gui-Min; O'Shaughnessy,Peter J.; Chubb,Curtis; Robaire,Bernard; Hardy,Matthew P.
Endocrinology 144(11): 5058-5064
Publication date: 2003
The role of IGF-I in Leydig cell maturation was studied by evaluationof: 1) steady state levels for nine mRNA species expressed specificallyin Leydig cells of 35- and 50-d-old IGF-I-null mice and wild-typecontrols; 2) protein levels for 17-hydroxylase/C17-20lyase, cholesterol side-chain cleavage, and type I 5-reductase(5R-1) in Leydig cells by immunocytochemistry; and 3) serumtestosterone (T) and testicular interstitial fluid IGF-I levels.Expression levels of all mRNA species associated with T biosynthesiswere lower in the absence of IGF-I stimulation. In contrast,androgen-metabolizing enzyme mRNA species had either normal(3-hydroxysteroid dehydrogenase) or higher expression (5R-1)levels in IGF-I-null mice (P < 0.05) relative to wild-typecontrols. None of the mRNA species studied changed developmentallyin the mutant, whereas there were increases or decreases betweend 35 and 50 in normal controls. Parallel trends were observedfor average Leydig cell 5R-1 immunostaining intensity. T levelsin mutants were initially higher during d 14-21, equivalentto normal on d 28, and then failed to increase pubertally, remainingat 30% of control levels (P < 0.01) in 90-d-old adult animals.In normal wild-type mice, interstitial fluid and plasma IGF-Ilevels were highest (P < 0.05) on d 24, indicating that theaction of this growth factor on the testis peaks during pubertaldevelopment. These results show that in the absence of IGF-I,there is a failure of adult Leydig cells to mature, and thatthe reduced capacity for T production is caused by disproportionateexpression of T biosynthetic and metabolizing enzymes.
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