Journal of Lipid Research, Vol 24, 1168-1175, Copyright © 1983 by Lipid Research, Inc.
Effects of estrogen and testosterone on the metabolism of mevalonate by the shunt pathway
PS Brady, RF Scofield, S Mann and BR Landau
Mevalonate is metabolized by a sterol-forming and a non-sterol-forming,
also called the "shunt", pathway. Effects of estrogen and testosterone
administration on the shunt activity were examined in male and female
Wistar and Sprague-Dawley rats. Shunt activity was determined in vivo from
the yield of expired 14CO2 following [5-14C]mevalonate injection. Total
mevalonate utilized was determined from the yield of expired 14CO2
following [1-14C]mevalonate injection. In the female, about 45% of
mevalonate appears to be metabolized via the shunt, and in the male about
20%. This difference between male and female rats is dependent on both
testosterone and estrogen, and apparently on testosterone to a greater
extent. Thus estrogen treatment produced a 20-35% increase in shunt
activity over castrated controls, while castration of males without
hormonal treatment resulted in about a 50% increase in shunt activity, and
testosterone administration returned castrated male and female shunt
activity to that of intact males, or nearly so. Light/dark cycle had no
effect in vivo on shunt activity, but may be critical in demonstrating sex
differences in shunt activity in kidney slices.