NEONATAL EXPOSURE TO XENOBIOTICS ALTERS ADULT HEPATIC PROTEIN-KINASE-C-ALPHA LEVELS AND TESTOSTERONE-METABOLISM - DIFFERENTIAL-EFFECTS BY DIETHYLSTILBESTROL AND PHENOBARBITAL

Hepatic enzymes that metabolize endogenous and xenobiotic compounds ha ve been shown to be altered in adult rate that had been exposed to xen obiotics as neonates. Protein kinase C (PKC) is important in intracell ular signaling and has been implicated in the regulation of hepatic mo nooxygenases. Therefore, we examined the effects of neonatal exposure to diethylstilbestrol (DES) and phenobarbital (PB) on hepatic microsom al testosterone metabolism and on the alpha form of protein kinase C ( PKC alpha) in adult rats. In adult males, neonatal exposure to DES alt ered adult testosterone metabolism such that 7 alpha-hydroxylation was increased by 58% but 2 alpha-, 16 alpha-, and 6 beta-hydroxylations a nd conversion to androstenedione were decreased 31-44%. In contrast, a dult males neonatally exposed to PB showed increased (20-27%) testoste rone 2 alpha- and 16 alpha-hydroxylations and androstenedione formatio n, but no effect was observed in the rate of 6 beta- or 7 alpha-hydrox ylations. Western blot analyses indicated that cytosolic PKC alpha lev els in male rats neonatally exposed to PB were decreased by similar to 63% relative to the vehicle control group but were not significantly altered in the DES males. The PKC alpha levels generally correlated (r = -.75) with 16 alpha-hydroxytestosterone formation in all samples. T hese results show that neonatal treatment with DES or PB differentiall y alters hepatic monooxygenase enzyme activities and PKC alpha levels in adult rats.