Disease relevance of CYP19A1

• Feminization of feathers in the Sebright cock is the result of increase in the activity of skin aromatase [1].
• Related to aromatase activity, persistence of too high levels of estrogens can explain the presence of oviducts, gonadal abnormalities and infertility in sex reversed females [2].
• However, the application of norethindrone (0.5 mg) to the chorioallantoic membrane of female alligator embryos in ovo resulted in significant hypertrophy of the ducts, indicating that norethindrone had an estrogenic effect in the alligator rather than acting as an aromatase inhibitor [3].

Psychiatry related information on CYP19A1

• The P450 aromatase (P450 arom) gene is asymmetrically expressed in a critical period for gonadal sexual differentiation in the chick [4].

High impact information on CYP19A1

• A single treatment of chicken embryos with an aromatase inhibitor (which blocks the synthesis of estrogen from testosterone) at a stage when their gonads were bipotential caused genetic females to develop a permanent male phenotype [5].
• In two henny-feathered breeds, the Sebright bantam and the Golden Campine, the synthesis of estrogen is increased as a consequence of increased activity of aromatase, a cytochrome P-450 enzyme that converts androgen to estrogen [6].
• 5-Azacytidine and sodium butyrate induce expression of aromatase in fibroblasts from chickens carrying the henny feathering trait but not from wild-type chickens [6].
• Nucleotide sequence analysis of the nine coding exons of the aromatase gene reveals that the predicted amino acid sequence is identical in all three strains [7].
• Aromatase mRNA in the extragonadal tissues of chickens with the henny-feathering trait is derived from a distinctive promoter structure that contains a segment of a retroviral long terminal repeat. Functional organization of the Sebright, Leghorn, and Campine aromatase genes [7].

Biological context of CYP19A1

• The expression patterns of cFoxL2 and aromatase transcripts were highly correlated during the sex-differentiation period (4.7-12.7 days of incubation) [8].
• To determine when during development the increased aromatase activity is expressed, we measured the enzyme in tissue slices of Sebright bantam and control bantam chickens of days 3, 12, and 18 of embryogenesis, on day 1 after hatching, and in mature birds [9].
• Aromatase activity is significantly reduced between 36 and 12 h before ovulation [10].
• The deduced amino acid sequence of leopard gecko aromatase cDNA showed 80% identity with that of turtles, 70% with humans and 77% with chickens [11].
• Posthatch treatment with EDP enhances sexual behavior but has no effect on attack; the aromatase inhibitor 1,4,6-Androstatrien-3,17-dione (ATD) blocked the suppression of peeping by testosterone but had no effect on testosterone-facilitated sexual behavior [12].

Anatomical context of CYP19A1

• Aromatase is expressed specifically in female gonads, but not male gonads, at the onset of sexual differentiation [13].
• The introduction of the cDNA clone into COS-1 cells results in the production of high levels of aromatase activity [14].
• In adult ovary follicular envelopes, apart from granulosa cells, cFoxL2 transcript and protein were detected at lower levels in theca cells where aromatase was present [8].
• In contrast, aromatase activity is very low in extraglandular tissues from control chickens and is undetectable in fibroblasts cultured from these tissues [6].
• In a second experiment (n = 3-5), we tested the specificity of the androgens in suppressing P4 production by granulosa cells by using the aromatase inhibitor 7-(4'-amino)phenylthio-4-androstene-3,17-dione [15].

Associations of CYP19A1 with chemical compounds

• P450-aromatase is the terminal estrogen-synthesizing enzyme and a key gene in avian sex determination [13].
• These findings establish that the cDNA clone encodes chicken ovarian aromatase and demonstrate that this protein can catalyze the three successive oxidation reactions necessary to form estrogen from androgen [14].
• Under the effects of Fadrozole (CGS 16949A), a nonsteroidal aromatase inhibitor, the right gonad generally becomes a testis, and the left gonad a testis or an ovotestis [16].
• Under the influence of LH, secretion of immunoreactive TCP is enhanced 3-fold and can be inhibited by up to 70% with aromatase inhibitor (1,4,6-androstatrien-3,17-dione) [17].
• In subsequent experiments, the effects of clomiphene on C17-20-lyase and aromatase activities were examined [18].

Other interactions of CYP19A1

• This finding suggests that FOXL2 lies upstream of aromatase in avian sex determination, but that it responds to depleted estrogen synthesis [13].
• Interstitial cells showed immunoreactivity for both P450SCC and P450C17, whereas a specific cell population of the theca externa, hereafter termed aromatase cells, showed immunoreactivity for P450AROM [19].
• Differential expression of genes for aromatase and estrogen receptor during the gonadal development in chicken embryos [20].
• DMRT1 expression was analyzed in chicken embryos during experimentally induced female-to-male sex reversal, using the aromatase enzyme inhibitor fadrozole [21].
• These results show that theca externa cells from preovulatory follicles of hen have enzymatic activities of 20 beta-reductase (from P5 and P4), 3 beta-hydroxysteroid dehydrogenase/5-4 isomerase (from P5 and DHEA), 17 beta-hydroxysteroid dehydrogenase (from A4 and T), and aromatase (from A4 and T) [22].

Analytical, diagnostic and therapeutic context of CYP19A1

• The spatial and temporal dynamics of cFoxL2 and aromatase expression were analyzed in parallel by using real-time quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry in attempt to investigate the possible role of cFoxL2 in the regulation of aromatase [8].
• The structural model described in this paper should be very useful for future structure-function studies of aromatase by site-directed mutagenesis [23].
• Specificity of antibody reaction was established by Western blot and by inhibition of aromatase activity in homogenates of chicken ovarian follicles determined by a radiometric assay [24].
• An 125I-labeled partial cDNA for the chicken aromatase P450 was used for in situ hybridization to chromosomes from primary chicken embryo fibroblast cultures [25].
• Following chromatography on gel filtration, anion exchange, dye affinity, and hydrophobic media, ovarian aromatase is purified up to 27-fold with 10-15% recovery [26].

References