EFFECT OF DEHYDROEPIANDROSTERONE ON PENTOSE-PHOSPHATE PATHWAY ACTIVITY IN THE RAT COLON

1. The effects of fasting and fasting followed by refeeding on the act ivities of the oxidative pentose pathway (OPP) and the non-oxidative p entose pathway (NOPP) were estimated by the rate of production of (CO2 )-C-14 from [1-C-14] glucose in isolated rat colonocytes, and the prod uction of hexose 6-phosphates from ribose 5-phosphate in rat colonic c ytosols, respectively. 2. The OPP activity in colonocytes from rats in the fasted state was 50% lower when compared to colonocytes from rats refed after a fast. This indicated induction of the rate-limiting enz yme of the OPP, glucose 6-P dehydrogenase (G6-PDH) in the latter insta nce. No effect on the maximal catalytic activity of the enzymes of the NOPP was seen in colonocytes from rats refed after a fast compared wi th colonocytes from rats in the fasted state. 3. Isolated colonocytes obtained from the distal colon of rats refed after a fast, showed a si gnificant decrease (30%) in OPP activity when incubated with 50 muM de hydroepiandrosterone (DHEA). A similar degree of inhibition was seen w ith 10 mM butyrate (P < 0.05). In contrast, using colonic cytosols, bo th DHEA and butyrate had no effect on the maximal catalytic activity o f the NOPP. 4. Intraperitoneal injection (i.p.) of DHEA in rats refed after a fast showed a significant increase in the maximal catalytic ac tivity of the NOPP in the distal colon (46%; P < 0.05). A similar elev ation in the maximal catalytic activity of the NOPP was seen in the di stal colon of DHEA treated pair-fed rats (43%; P < 0.05). No significa nt change was seen in maximal catalytic activity of the NOPP in colono cytes obtained from the proximal colon of DHEA treated rats in both ad libitum fed and pair-fed rats. 5. DHEA administration is postulated t o increase the maximal catalytic activity of the NOPP as a compensator y response to a lowered OPP activity. This increased potential for glu cose flux through the NOPP can presumably replace the deficit in suppl y of phosphorylated sugars needed for the actively dividing colonocyte s in the distal colon.