Elevated expression of liver gamma-cystathionase is required for the maintenance of lactation in rats

Liver gamma-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 gamma-cystathionase and the intertissue flux of glutathi one during lactation, we used lactating and virgin rats fed liquid diets. V irgin 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 previou s day by lactating rats (high protein diet-fed rats); the other virgin grou p was fed the normal liquid diet (control). The expression and activity of liver gamma-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)] relea sed per gram of liver did not differ in lactating rats or in high protein d iet-fed rats, but it was significantly higher in these two groups than in c ontrol virgin rats. Liver size and the GSH + GSSG released by total liver w ere significantly higher in lactating rats than in high protein diet-fed vi rgin rats, and this difference was similar to the amount of glutathione tak en up by the mammary gland (454.2 +/- 36.0 nmol/min). The uptake of total g lutathione 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-cy steine delivery to the lactating mammary gland, which lacks gamma-cystathio nase activity. This emphasizes the physiologic importance of the increased expression and activity of liver gamma-cystathionase during lactation.