Inhibitory actions of interleukin-1 beta on steroidogenesis in primary cultures of neonatal rat testicular cells.

Interleukin-1 is an important cytokine produced by activated macrophages. Because macrophages have been localized in the testis and interleukin-1 bioactivity has been observed in the testis, the potential effect of interleukin-1 on gonadotropin-stimulated androgen production was investigated using primary cultures of neonatal rat testis cells. Cells were incubated for 3 days before change of medium and treatment with human chorionic gonadotropin and interleukin-1. After 3 additional days medium testosterone and progesterone levels were determined. Human chorionic gonadotropin treatment (0.30-30 micrograms/l) of cultured cells stimulated testosterone production dose-dependently with a maximum increase greater than 18-fold over control values. Although interleukin-1 treatment alone did not affect testosterone production, the concomitant addition of interleukin-1 beta (0.5-5 X 10(3) U/l) caused a dose-dependent decrease of human chorionic gonadotropin action, with 50% inhibition occurring at 1.4 X 10(3) U/l (0.6 X 10(-11) mol/l; N = 5 experiments). Interleukin-1 beta also inhibited forskolin- and dibutyryl cAMP-stimulated testosterone production. The suppression of human chorionic gonadotropin-induced testosterone production by testis cells was accompanied by increased (greater than 3-fold) progesterone levels. Moreover, the conversion of exogenously added androgen precursors (progesterone and 17 alpha-hydroxyprogesterone) to testosterone by human chorionic gonadotropin-stimulated cells was suppressed by interleukin-1 beta suggesting that the activity of the 17 alpha-hydroxylase enzyme may be decreased.(ABSTRACT TRUNCATED AT 250 WORDS)