Effects of estrogen and testosterone on the metabolism of mevalonate by the shunt pathway.

• Main Authors: P S Brady, R F Scofield, S Mann, B R Landau
• Format: Article
• Language: English
• Published: Elsevier 1983-09-01
• Series: Journal of Lipid Research
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520379001

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.