Origins of fecal neutral steroids in rats

The origins of rat fecal neutral steroids were studied in male and female animals fed a sterol-free diet and maintained in an isotopic steady state. The specific activity of fecal cholesterol was found to be consistently lower than that of plasma cholesterol and of the fecal bile acids, indicating that a considerable portion of the fecal neutral steroids was derived from cholesterol not in equilibrium with the rapidly exchangeable pool of body cholesterol. This non-exchanging fraction of neutral steroids was larger in male than in female rats; it appeared to have at least two origins: skin surface lipids licked off fur, and sterols newly synthesized by the intestinal mucosa and secreted into the gut lumen. When the ingestion of skin sterols rich in cholesterol precursors was minimized, the proportion of the non-exchanging fraction of fecal neutral sterols fell somewhat, but the output of cholesterol precursors dropped markedly. This suggests that a significant portion of the non-exchanging fecal cholesterol fraction originated in the intestinal wall by secretion. It can be concluded that the fecal neutral steroids of rats originate primarily from three sources: 1) de novo cholesterol synthesis by the intestinal mucosa, 2) ingested dietary, skin, and fecal sterols, and 3) a rapidly exchangeable cholesterol pool excreted through bile, the intestinal wall, or both.