Disease relevance of cyp19a1a

• Ethynylestradiol provoked marked mortality (approximately 50%) and delayed development of larvae as well as sterility of adult females, possibly related to alterations in aromatase gene expression [1].

High impact information on cyp19a1a

• We isolated two cyp19 cDNAs, termed cyp19a and cyp19b, respectively, from zebrafish [2].
• The expression of duplicated cyp19 genes at two different tissues highlights the evolutionary significance of maintaining two active genes on duplicated zebrafish chromosomes for specific functions in the ovary and the brain [2].
• The early embryonic expression of P450aromB and P450aromA isoforms, and differences in developmental programming and estrogen regulation, imply independent regulatory mechanisms and unique functions during major morphogenetic and differentiative events [3].
• Assessment of xenoestrogens using three distinct estrogen receptors and the zebrafish brain aromatase gene in a highly responsive glial cell system [4].
• The brain cytochrome P450 aromatase (Aro-B) in zebrafish is expressed in radial glial cells and is strongly stimulated by estrogens (E(subscript)2(/subscript)) ; thus, it can be used in vivo as a biomarker of xenoestrogen effects on the central nervous system [4].

Biological context of cyp19a1a

• The cyp19a promoter region has TATA and CAAT boxes, a steroidogenic factor-1 (SF-1) binding site, and two aryl hydrocarbon receptor (AhR)/AhR nuclear translocator factor (ARNT) binding motifs [5].
• Both genes have multiple potential SRY/SOX binding sites (16 and 8 in cyp19b and cyp19a, respectively) [5].
• Multiple cytochrome P450 aromatase (P450arom) cDNAs that derive from separate gene loci (cyp19a and cyp19b) are differentially expressed in brain (P450aromB>>A) and ovary (P450aromA>>B) and have a different developmental program (B>>A) and response to estrogen upregulation (B only) [5].
• Phylogeny, expression and enzyme activity of zebrafish cyp19 (P450 aromatase) genes [6].
• Seasonal plasticity of brain aromatase mRNA expression in glia: divergence across sex and vocal phenotypes [7].

Anatomical context of cyp19a1a

• We found that the onset of amh expression occurred while gonads were still undifferentiated and sox9a and cyp19a1a were already expressed [8].
• In adult ovaries, amh and cyp19a1a were expressed in granulosa cells surrounding the oocytes, and sox9b was expressed in a complementary fashion in the ooplasm of oocytes [8].
• In male mammalian embryos, Sox9 activates expression of Amh, which initiates the regression of the Mullerian ducts and inhibits the expression of aromatase (Cyp19a1), the enzyme that converts androgens to estrogens [8].
• Both aromatase enzymes encoded by these two genes are functional in COS-1 cells and they can use androstenedione and testosterone equally efficiently [6].
• When microinjected into fertilized zebrafish eggs, a cyp19b promoter-driven green fluorescent protein (GFP) reporter (but not cyp19a) is expressed in neurons of 30-48 hpf embryos, most prominently in retinal ganglion cells (RGCs) and their projections to optic tectum [5].

Associations of cyp19a1a with chemical compounds

• Distinct cytochrome P450 aromatase isoforms in zebrafish (Danio rerio) brain and ovary are differentially programmed and estrogen regulated during early development [3].
• Here, we quantified seasonal changes in brain aromatase mRNA expression in the inter- and intrasexually dimorphic sonic motor nucleus (SMN) and in the preoptic area (POA) in males and females in relation to seasonal changes in circulating steroid hormone levels and reproductive behaviors [7].
• The Cyp19 gene product aromatase converts testosterone into 17 beta-estradiol, and when inhibited leads to male to female sex reversal [9].
• The effect of DES (0.01 microM) was similar to 1 microM E(2) (three- to four-fold higher than control), but BPA was less effective (<threefold increase at 10 microM). mRNA levels of the predominant ovarian isoform (P450aromA) were unchanged by estrogen [10].
• The primary culture consisted of three major types of cells, presumably the fibroblasts, the thecal cells and the granulosa cells, according to the morphological features, histochemical staining for 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and RT-PCR for aromatase [11].

Other interactions of cyp19a1a

• Several physiological endpoints that may be affected by endocrine disrupters were analysed, specifically vitellogenin (VTG) concentration, estradiol (E2), testosterone (T), and 11-ketotestosterone (KT) content, brain aromatase activity and gene expression of CYP19A1 and CYP19A2 in the testis [12].

Analytical, diagnostic and therapeutic context of cyp19a1a

• As a first step toward understanding estrogen's role in neurodevelopment, a PCR cloning strategy was used to isolate complementary DNAs encoding two distinct cytochrome P450 aromatase isoforms in adult zebrafish (Danio rerio) brain and ovary (termed P450aromB and P450aromA, respectively) [3].
• On Northern blots, a single 4.4-kb transcript of the P450aromB subtype was identified in brain, and a 2.1-kb transcript of the P450aromA subtype in ovary, but RT-PCR showed a degree of overlapping expression [3].

References