Lipoproteins stimulate androgen production by cultured rat testis cells

The effects of human high density lipoprotein (hHDL), human low density lipoprotein (hLDL), and rat high density lipoprotein (rHDL) on androgen production by cultured rat testis cells were investigated. Enzymatically dissociated testis cells from hypophysectomized adult rats were cultured in a serum-free medium. During the first 2 days of culture, the addition of human or rat lipoprotein alone stimulated testis cell testosterone (T) production by 100 to 250% in a dose-dependent manner. Likewise, treatment with hCG caused a 2.5-fold increase in T production. Furthermore, the effect of lipoproteins plus hCG was synergistic; the stimulation of T production by concomitant treatment with hCG and lipoproteins was greater than the sum of each added individually. Rat HDL augmented hCG stimulated T production in a concentration-dependent manner and maximum synthesis was achieved at 100 micrograms protein/ml (240% increase) with an ED50 value of 25 micrograms/ml rHDL. At low concentrations (10-30 micrograms protein/ml), all lipoproteins tested had similar stimulatory effects on T production but at the highest dose tested (300 micrograms protein/ml), hHDL was more effective than rHDL. The stimulatory effect of lipoprotein was shown to be time-dependent. Maximum stimulation of T production by lipoprotein was seen during the initial 48 h of culture, whereas lipoproteins were ineffective during the first 5 h and during days 8 to 10 of culture. The present data are consistent with the concept that lipoproteins provide cholesterol substrate while gonadotropins stimulate tha rate limiting enzyme(s) which convert cholesterol to T. This primary culture model of testis cells in serum-free medium is responsive to serum lipoproteins and offers a unique opportunity to study the direct effect of lipoproteins and gonadotropins on testicular steroidogenesis.