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

1. The effects of fasting and fasting followed by refeeding on the activities of the oxidative pentose pathway (OPP) and the non-oxidative pentose pathway (NOPP) were estimated by the rate of production of (CO2)-C-14 from [1-C-14] glucose in isolated rat colonocytes, and the production of hexose 6-phosphates from ribose 5-phosphate in rat colonic cytosols, 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 enzyme of the OPP, glucose 6-P dehydrogenase (G6-PDH) in the latter instance. No effect on the maximal catalytic activity of the enzymes of the NOPP was seen in colonocytes from rats refed after a fast compared with colonocytes from rats in the fasted state. 3. Isolated colonocytes obtained from the distal colon of rats refed after a fast, showed a significant decrease (30%) in OPP activity when incubated with 50 muM dehydroepiandrosterone (DHEA). A similar degree of inhibition was seen with 10 mM butyrate (P < 0.05). In contrast, using colonic cytosols, both DHEA and butyrate had no effect on the maximal catalytic activity of the NOPP. 4. Intraperitoneal injection (i.p.) of DHEA in rats refed after a fast showed a significant increase in the maximal catalytic activity of the NOPP in the distal colon (46%; P < 0.05). A similar elevation in the maximal catalytic activity of the NOPP was seen in the distal colon of DHEA treated pair-fed rats (43%; P < 0.05). No significant change was seen in maximal catalytic activity of the NOPP in colonocytes obtained from the proximal colon of DHEA treated rats in both ad libitum fed and pair-fed rats. 5. DHEA administration is postulated to increase the maximal catalytic activity of the NOPP as a compensatory response to a lowered OPP activity. This increased potential for glucose flux through the NOPP can presumably replace the deficit in supply of phosphorylated sugars needed for the actively dividing colonocytes in the distal colon.