P450C26 is known as an enzyme that catalyzes 26-hydroxylation of
cholesterol, 25-hydroxylation of vitamin D3, and 4-hydroxylation of retinoic acid. 26-Hydroxycholesterol blocks endogenous cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) synthase, HMGCoA reductase, and low-density lipoprotein (LDL) receptor gene expression. Northern blot analysis revealed that the P450c26/25 cDNA hybridizes with a 2.4-kb RNA from rat liver and unstimulated ovaries (Su et al., 1990).
General function
Metabolism, Enzyme, Oxidoreductase
Comment
Cellular localization
Mitochondrial
Comment
Ovarian function
Steroid metabolism
Comment
Yoshida et al. (1999) results suggest that P450C26 cooperated with 20-HSD in the reduction of progesterone release from the rat luteal tissue at the end of the functional luteal phase.
Rennert et al. (1990) characterized the enzyme generating 26-hydroxycholesterol in the rat ovary. They suggest that 26-hydroxycholesterol is an intracrine regulator that controls cellular sterol metabolism.
Expression regulated by
FSH
Comment
Treatment of rats with pregnant mare's serum gonadotropin resulted in a fivefold increase in the 2.4-kb mRNA as well as the appearance of a 2.1-kb mRNA species in the ovaries (Su et al., 1990).
Ovarian localization
Granulosa, Luteal cells
Comment
From a subtracted cDNA library of rat luteal tissue, where cDNA fragments in functional luteal tissue were subtracted from those in regressing
luteal tissue, a cDNA clone corresponding to 26-cholesterol hydroxylase (P450C26) was obtained (Yoshida et al., 1999) Rennert et al. (1990) found that 26-hydroxycholesterol inhibits human ovarian cell sterol synthesis, and that luteinized human granulosa cells contain 26-hydroxylase messenger RNA (mRNA).
Follicle stages
Corpus luteum
Comment
P450C26 mRNA was examined in corpora lutea from pseudopregnant rats by Northern blot or reverse transcription-polymerase chain reaction or both. P450C26 mRNA was ubiquitously expressed in corpora lutea, and its expression increased toward the end of pseudopregnancy (Yoshida et al., 1999)