Occurrence and metabolism of 20α-hydroxycholesterol in bovine adrenal preparations

Oxysterols are allosteric activators of the oncoprotein Smoothened

“…The EC50 of nat -20(S)-OHC for Hh target gene induction (~3 μM) is in the same range as EC50 values (4–7 μM) reported for the activation of LXRαreceptors by the endogenous ligands 24-OHC and 22-OHC 19,20 . While the concentration of nat -20(S)-OHC in Hh-responsive cells or embryos has not been carefully measured, concentrations of oxysterols in tissues have been estimated to be in the 0.1–10μM range 47,48 . While this seems lower than our measured EC50 for nat-20(S)-OHC, it is important to note that the affinity constants (K d values) for oxysterol-protein interaction are often more than an order of magnitude lower than EC50s, presumably because much of the oxysterol is not available to the receptor when its added to cell culture 19 .…”

Tracking the Subcellular Fate of 20(S)-Hydroxycholesterol with Click Chemistry Reveals a Transport Pathway to the Golgi

“…Although 20(S)-OHC has been previously detected in tissues (7,41), very little is known about its biosynthetic pathways, distribution, or trafficking. In our previous studies of Hh signaling, we synthesized 20(S)-yne, an alkynyl derivative of 20(S)-OHC, that retained activity as a direct SMO agonist ( Fig.…”

“…Oxysterols have three properties distinct from cholesterol that make them ideally suited to function as second messengers in signaling pathways as follows: cellular concentrations 3 orders of magnitude lower than cholesterol (6,7); transfer rates between membranes that are ϳ50-fold higher than cholesterol (8 -10), and shorter half-lives compared with cholesterol (11).…”

Other conceivable renditions of some of the oxidative processes used in the biosynthesis of steroid hormones

“…This matter was discussed at length in [2]. There it was recalled that both 20S-hydroxycholesterol [12] and 17␣,20␣-dihydroxycholesterol [13] were converted into 17-hydroxypregnenolone by an enzyme(s) present in the mitochondrial fraction of adrenals. These findings were unexpected because the enzyme, dubbed 17-hydroxylase, is usually found in the microsomal fraction.…”