CYP11A1

CYP11A1

A gene on chromosome 15q23-q24 that encodes a member of the cytochrome P450 superfamily of enzymes, which catalyse reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. CYP11A1 localises to the mitochondrial inner membrane and catalyses the conversion of cholesterol to pregnenolone, the first and rate-limiting step in the synthesis of the steroid hormones.
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In these pathways, ovarian gene expression of Luteinizing Hormone/Choriogonadotropin Receptor (Lhcgr), Steroidogenic Acute Regulatory Protein (Star), Cytochrome P450 Family 11 Subfamily A Member 1 (Cyp11a1), Hydroxy-Delta-5-Steroid Dehydrogenase, 3 Beta- and Steroid Delta Isomerase 1 (Hsd3b1), Cytochrome P450 Family 17 Subfamily A Member 1 (Cyp17a1), Follicle Stimulating Hormone Receptor (Fshr), Cytochrome P450 Family 19 Subfamily A Member 1 (Cyp19a1), and Hydroxysteroid 17-Beta Dehydrogenase 1 (Hsd17b1) were examined (Figure 6A).
Nonstandard abbreviations: StAR, steroidogenic acute regulatory protein; CYP11A1, P450 side-chain cleavage enzyme; CYP11B1, 11[beta] hydroxylase; CYP11B2, aldosterone synthase; CYP17A1, 17 [alpha]-hydroxylase/ 17,20-lyase; CYP21A2,21-hydroxylase; HSD3B2, 3[beta]-hydroxysteroid dehydrogenase type 2; HSD11B1, 11[beta]-hydroxysteroid dehydrogenase type 1; HSD11B2, 11[beta]-hydroxysteroid dehydrogenase type 2; HSD17B, 17 [beta]-hydroxysteroid dehydrogenase; SRD5A2, 5[alpha]-reductase type 2; CYP19A1, P450 Aromatase; SULT2A1, sulfotransferase 2A1.
In fact, VPA significantly reduced gene and protein expressions of StAR, CYP11A1, and androgen receptor, responsible for testosterone production (Gustavsen et al., 2009; Glister et al.; Iamsaaed et al., 2017a).
The cholesterol is first imported into the mitochondria by steroidogenic acute regulatory protein (StAR), and cytochrome P450 side chain cleavage enzyme (CYP11A1) then cleaves the side-chain of cholesterol to produce pregnenolone [1].
1,25D3 prevents CD8(+)Tc2 skewing and asthma development through VDR binding changes to the Cyp11a1 promoter.
Linkage studies of 37 candidate genes predicted strong association of follistatin and nominal association of CYP11A1 gene in affected siblings with hyperandrogenemia and PCOS related traits.
The family of cytochromes P450 [43, 44] that are activated by I/R injury, to which the CYP11A1, the 21-hydroxylase (CYP21) and the aldosterone synthase (CYP11B2), the CYP11A1, and the CYP11B2 belong, is found in the internal mitochondrial membrane, while the CYP21 is found in the smooth endoplasmic reticulum (ER).
Its main function consists in facilitating the migration of cholesterol from the outer to the inner mitochondrial membrane for its conversion into pregnenolone by the cholesterol side-chain cleavage enzyme (CYP11A1) [8, 9].
Watanabe et al., "Epidermal growth factor and c-Jun act via a common DNA regulatory element to stimulate transcription of the ovine P-450 cholesterol side chain cleavage (CYP11A1) promoter," The Journal of Biological Chemistry, vol.
Leptin can regulate Leydig cell's steroid production through the transcriptional regulation of different steroidogenic genes such as those encoding the steroid acute regulatory protein (Star) and the cholesterol side chain cleavage enzyme P450ssc (encoded by Cyp11a1 gene).
Steroidogenesis is modulated through the regulation of the genes involved in the hypothalamic-pituitary--steroidogenetic axis, such as: STAR, CYP11A1, CYP17A1, CYP19A1, LH and INHA(30).
The P450 s enzyme (CYP11A1) is present in the internal membrane of the mitochondria converting cholesterol into pregnenolone, mainly in the theca interna cells (30).