Fibroblast Growth Factor Inhibits Luteinizing Hormone-Stimulated Androgen Production by Cultured Rat Testicular Cells*

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Abstract
The effect of fibroblast growth factor (FGF) on LH-stimulated testosterone production was investigated using primary cultures of rat testicular cells. Testicular cells obtained from neonatal rats (8-9 days of age) were maintained in culture for 3 days and then challenged with LH with or without basic FGF. After 3 additional days of culture, the media were collected for steroid RIA. LH treatment of cultured cells stimulated testosterone production in a dose-dependent fashion whereas FGF alone did not affect androgen biosynthesis. In contrast, cotreatment with FGF caused a dose-dependent decrease of LH-stimulated testosterone production, with an IC50 value of 1.1 .times. 10-9 M (as calculated from three separate experiments). The inhibitory effect of FGF was evident 24 h after the initiation of treatment and this effect was reversible 1 day after the cessation of FGF treatment. The inhibition of LH-induced testosterone production by FGF (maximal inhibition > 90%) was accompanied by a 12-fold increase in progesterone levels, suggesting that the inhibitory effect of FGF was distal to the step of progesterone formation. FGF also inhibited forskolin (10-5M)- and (Bu)2cAMP (5 .times. 10-4 M)-stimulated testosterone production. Furthermore, FGF inhibited the conversion of exogenously added androgen precursors (progesterone and 17.alpha.-hydroxyprogesterone) to testosterone in LH-stimulated cultures indicating that FGF might inhibit 17.alpha.-hydroxylase activity. The concept of a direct testicular action of FGF was further supported by the demonstration of high affinity (Kd: 3.9 .times. 10-10 M; n = 3 experiments) and low capacity (46,900 sites per cell) FGF receptors in cultured testis cells. The binding of [125I]FGF was inhibited by basic and acidic FGF but not by several other growth factors. In conclusion, we suggest that FGF binds to testicular cells and inhibits LH-stimulated testosterone production by inhibiting, at least partially, 17.alpha.-hydroxylase enzyme activities. Because FGF has been purified from testis extracts, this growth factor may have intratesticular paracrine or autocrine functions.

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