Prolactin increases the hepatic content of mu-class subunits of glutathione S-transferase in the rat.

Hepatic glutathione S-transferase (GST) activity is increased in postpartum female rats, a phenomenon that depends on the lactation stimulus. Here we evaluated the effect of prolactin (PRL) administration on hepatic enzyme activity and on the expression of the major subunits of the alpha- (rGSTA1, rGSTA2, rGSTA3) and mu-classes (rGSTM1, rGSTM2). A similar study was conducted in lactating (LM) and in nonlactating (NLM) mother rats 14 days after delivery and in virgin female rats (V). Ovine PRL (oPRL) was administered to ovariectomized rats at daily doses of 75, 150, 200, and 300 microg/100 g b.wt. (PRL1, PRL2, PRL3, and PRL4, respectively) for 4 consecutive days. GST activity was measured using 1-chloro-2,4-dinitrobenzene as substrate. The relative content of the different subunits was determined by Western blot. oPRL produced a dose-dependent increase in GST activity (60% at the highest dose). Subunit analysis performed in PRL2 and PRL4 revealed a substantial enhancement in rGSTM2 and to a lesser extent in rGSTM1, in response to oPRL. The effect was also dose-dependent. alpha-Class subunits were increased only slightly after hormone treatment. A 60% increase in GST activity was observed for LM relative to NLM and V. As was observed for PRL treatment, the increase was associated with changes in the expression of mu-class subunits whereas alpha-class subunits were not affected by lactation. Taken together these data would indicate a role of PRL in regulating GST activity postpartum via an increase in the content of mu-class subunits, particularly rGSTM2.