NCBI Summary:
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the mitochondrial inner membrane and is involved in the conversion of progesterone to cortisol in the adrenal cortex. Mutations in this gene cause congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. Transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]
General function
Enzyme
Comment
Cellular localization
Mitochondrial
Comment
Ovarian function
Steroid metabolism
Comment
Expression regulated by
LH
Comment
Cyp11b1 is induced in the murine gonad by luteinizing hormone/ human chorionic gonadotropin and involved in the production of 11-ketotestosterone, a major fish androgen; conservation and evolution of androgen metabolic pathway. Yazawa T et al. We have shown previously that Cyp11b1, an 11beta-hydroxylase responsible for glucocorticoid biosynthesis in the adrenal gland, was induced by cAMP in androgen-producing Leydig-like cells derived from mesenchymal stem cells. We found that Cyp11b1 was induced in male Leydig cells, or female theca cells, when hCG was administered in immature mice. Expression of Cyp11b1 in rodent gonads caused the production of 11-ketotestosterone (11-KT), a major fish androgen, which induces male-differentiation or spermatogenesis in fish. As in teleosts, plasma concentrations of 11-KT were elevated in hCG-treated mice. In contrast to teleosts, however, plasma concentrations of 11-KT were similar in both sexes, despite levels of testosterone, a precursor substrate, being about 20-times higher in male mice. Since expression of Hsd11b2, a type 2 11beta-hydroxysteroid dehydrogenase (11beta-HSD2), was much higher in the mouse ovary than in the testis, conversion of testosterone into 11-KT may occur more efficiently in the ovary. In a luciferase reporter system that was responsive to and activated by androgens, 11-KT efficiently activated mammalian androgen receptor-mediated transactivation. Our results suggest that the androgen metabolic pathway is conserved between teleosts and mammals, despite sexual dominancy and reproductive functions of 11-KT being altered during evolution.
Ovarian localization
Granulosa, Theca
Comment
Detection and activity of 11 beta hydroxylase (CYP11B1) in the bovine ovary. Amweg AN et al. (2017) Glucocorticoids (GCs) such as cortisol and corticosterone are important steroid hormones with different functions in intermediate metabolism, development, cell differentiation, immune response and reproduction. In response to physiological and immunological stress, adrenocorticotropic hormone (ACTH) acts on the adrenal gland by stimulating synthesis and secretion of GCs. However, there is increasing evidence that GCs may also be synthesized by extra-adrenal tissues. Here, we examined the gene and protein expression of the enzyme 11β-hydroxylase P450c11 (CYP11B1), involved in the conversion of 11-deoxycortisol to cortisol, in the different components of the bovine ovary, and determined the functionality of CYP11B1 in vitro. CYP11B1 mRNA was expressed in granulosa and theca cells in small, medium and large antral ovarian follicles and CYP11B1 protein was expressed in medium and large antral follicles. After stimulation by ACTH, we observed an increased secretion of cortisol by the wall of large antral follicles. We also observed a concentration-dependent decrease in the concentration of cortisol in response to metyrapone, an inhibitor of CYP11B1. This decrease was significant at 10-5 µM metyrapone. In conclusion, this study demonstrated for the first time the presence of CYP11B1 in the bovine ovary. This confirms that there could be a local synthesis of GCs in the bovine ovary and therefore a potential endocrine responder to stress through these hormones.//////////////////
Follicle stages
Antral, Preovulatory
Comment
Phenotypes
Mutations
1 mutations
Species: human
Mutation name: None
type: naturally occurring fertility: fertile Comment: A novel missense mutation, GGC(Arg454) --> TGC(Cys), of CYP11B1 gene identified in a Chinese family with steroid 11beta-hydroxylase deficiency. Ye ZQ et al. BACKGROUND: Steroid 11beta-hydroxylase deficiency (11beta-OHD), an autosomal recessive inherited disease, accounts for 5% - 8% of congenital adrenal hyperplasia. It was scarcely reported in China. This article reports two Chinese girls with 11beta-OHD. METHODS: The two patients were sisters and presented with hypertrichosis, skin pigmentation, laryngeal prominence and virilization of external genitalia. The patients were followed up for their clinical symptoms and signs, hormone profile, and adrenal image. The genomic deoxyribonucleic acids of the patients and their parents were isolated. 11beta-hydroxylase gene (CYP11B1) was amplified by polymerase chain reaction and directly sequenced. RESULTS: Hormone tests showed that serum cortisol was in the low limit of normal range, whereas the concentrations of adrenocorticotropic hormone, testosterone and progesterone were much higher than those of normal adult females. There were obvious adrenal hyperplasia and advance of bone age. After 11 months of treatment with dexamethasone, the skin pigment became regressed; the breast, uterus and ovary gradually developed and normal menstrual cycle started while the manifestations of virilization did not change. A single point mutation of CYP11B1 (R454C, GGC --> TGC) in all the members of this family was detected. The sisters were homozygous and their parents were heterozygous. CONCLUSIONS: The clinical manifestation of 11beta-OHD is complicated. The manifestation of virilization could not regress after treatment with dexamethasone. The novel missense mutation of CYP11B1 (R454C, GGC --> TGC) is the pathogenesis of 11beta-OHD at least in some Chinese patients.