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For all you progesterone addicts, make sure it doesn't lower your cholesterol too much, as progesterone reduces cholesterol, if these studies are right.
Boots for Achilles: progesterone's reduction of cholesterol is a second-order adaptation.
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Progesterone Inhibits Cholesterol Biosynthesis in Cultured Cells
Boots for Achilles: progesterone's reduction of cholesterol is a second-order adaptation.
Progesterone and cholesterol are both vital to pregnancy. Among other functions, progesterone downregulates inflammatory responses, allowing for maternal immune tolerance of the fetal allograft. Cholesterol a key component of cell membranes, is important in intracellular transport, cell signaling, nerve conduction, and metabolism Despite the importance of each substance in pregnancy, one exercises an antagonistic effect on the other, as periods of peak progesterone correspond with reductions in cholesterol availability, a consequence of progesterone's negative effects on cholesterol biosynthesis.
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Progesterone Inhibits Cholesterol Biosynthesis in Cultured Cells
Cells acquire cholesterol through endogenous synthesis and through receptor-mediated uptake of cholesterol-rich low density lipoprotein (LDL). Esterification of LDL-derived cholesterol is catalyzed by acyl-CoA:cholesterol acyltransferase (ACAT) in the endoplasmic reticulum (ER). Progesterone inhibits esterification, and, although the mechanism of inhibition is not completely understood, this inhibition results from progesterone's ability to inhibit the activity of multiple drug resistance (MDR) P-glycoproteins (P. DeBry and J. E. Metherall, submitted for publication). In the current manuscript, we demonstrate that progesterone inhibits cholesterol biosynthesis resulting in the accumulation of a number of sterol precursors. In Chinese hamster ovary (CHO) cells, high concentrations (100 μM) of progesterone completely blocked cholesterol production, resulting in the accumulation of lanosterol and a lanosterol precursor. Lower concentrations (40 μM) of progesterone cause plasma membrane accumulation of several sterol products. The majority of these sterols are precursors of cholesterol since they were efficiently converted to cholesterol upon removal of progesterone from the culture medium. Although very high concentrations (>200 μM) of progesterone killed CHO cells, their growth was restored by the addition of cholesterol to the growth medium, indicating that progesterone toxicity resulted from cholesterol auxotrophy. The effect of progesterone was not unique to CHO cells; progesterone also inhibited cholesterol biosynthesis in all human cell lines tested. These observations suggest that a common progesterone-sensitive pathway is involved in both cholesterol biosynthesis and the processing of LDL-derived cholesterol.