Elevated Expression of Liver γ-Cystathionase Is Required for the Maintenance of Lactation in Rats

Abstract

Liver γ-cystathionase activity increases in rats during lactation; its inhibition due to propargylglycine is followed by a significant decrease in lactation. This is reversible by N-acetylcysteine administration. To study the role of liver γ-cystathionase and the intertissue flux of glutathione during lactation, we used lactating and virgin rats fed liquid diets. Virgin rats were divided into two groups as follows: one group was fed daily a diet containing the same amount of protein that was consumed the previous day by lactating rats (high protein diet–fed rats); the other virgin group was fed the normal liquid diet (control). The expression and activity of liver γ-cystathionase were significantly greater in lactating rats and in high protein diet–fed virgin rats compared with control rats. The total glutathione [reduced glutathione (GSH) + oxidized glutathione (GSSG)] released per gram of liver did not differ in lactating rats or in high protein diet–fed rats, but it was significantly higher in these two groups than in control virgin rats. Liver size and the GSH + GSSG released by total liver were significantly higher in lactating rats than in high protein diet–fed virgin rats, and this difference was similar to the amount of glutathione taken up by the mammary gland (454.2 ± 36.0 nmol/min). The uptake of total glutathione by the lactating mammary gland was much higher than the uptakes of free L-cysteine and L-cystine, which were negligible. These data suggest that the intertissue flux of glutathione is an important mechanism of L-cysteine delivery to the lactating mammary gland, which lacks γ-cystathionase activity. This emphasizes the physiologic importance of the increased expression and activity of liver γ-cystathionase during lactation.