Disease relevance of CYP19

• The ratio of testosterone to estradiol was not different between treatments for the initial 30 h of infusion, but was significantly reduced thereafter in response to insulin (P < 0.01), suggesting that hyperinsulinemia increased follicular aromatase activity [1].

High impact information on CYP19

• Ovine fetal ovaries exposed to AMH release testosterone instead of estradiol, an endocrine sex reversal due to suppression of aromatase activity [2].
• Cell viability, cell number, and the amount of aromatase in granulosa cells were not altered by alpha(2)-M [3].
• Before the time point at which dominant follicles can be distinguished by virtue of their deviation in size and growth rate, transcripts for inhibin beta A, apolipoprotein E receptor 2, and p450 aromatase were elevated specifically in the one to three largest follicles [4].
• The 5'-flanking region of the ovarian promoter of the bovine CYP19 gene contains a deletion in a cyclic adenosine 3',5'-monophosphate-like responsive sequence [5].
• Our experiments demonstrate that six transcript variants of the bovine Cyp19 gene, including 9-11 exons, are expressed with tissue-specific preferences [6].

Biological context of CYP19

• In cattle, the CYP19 locus comprises the aromatase cytochrome P450-encoding gene (CYP19) and a homologous pseudogene (CYP19P1) [7].
• (2) Within the chromosome region 10q26 CYP19 and CYP19P1 are arranged "tail-to-head", being separated by a distance of about 24 kb between the labeled clones [7].
• The aim of the present investigation was the isolation and comparative sequence analysis of the bovine aromatase cytochrome P-450 transcript (bCyp19) from a placental lambda gt10 cDNA library [8].
• The data suggest that promoter-2-derived high-level expression but not promoter-1.1-derived low-level expression of Cyp19 might be controlled by cell-type-specific DNA methylation [9].
• From the present data it can be concluded: (a) that the ovine genome contains two copies of Cyp19 of which only one is transcribed and may encode a functional protein; and (b) that in spite of being closely related species, sheep and cattle have remarkable differences concerning tissue-specific transcript distribution and presumable promoter usage [10].

Anatomical context of CYP19

• Distinct regulation by steroids of messenger RNAs for FSHR and CYP19A1 in bovine granulosa cells [11].
• Transcriptional start sites of Cyp19 were examined in granulosa cells, placenta, testis, adrenal gland, and brain, employing 5'-RACE (rapid amplification of complementary DNA ends) and primer extension [6].
• The objective of this study was to investigate changes in expression of mRNAs encoding FSH receptor (FSHr), LH receptor (LHr), cytochrome P450 side-chain cleavage (P450(scc)), cytochrome P450 17alpha-hydroxylase (P450(c17)), and cytochrome P450 aromatase (P450(arom)) during recruitment and selection of bovine ovarian follicles [12].
• For a better characterisation of classes the mRNA expressions of FSH receptor, LH receptor and aromatase cytochrome P450 in theca interna (TI) and granulosa cells (GC) were determined [13].
• Cyp19, the key gene of oestrogen biosynthesis, is expressed at very different concentrations and from different promoters in bovine granulosa cells (GCs) and in pregnant corpora lutea (CL), respectively [9].

Associations of CYP19 with chemical compounds

• Effects of E2 and T on CYP19A1 were blocked by ICI 182,780, indicating mediation by estrogen receptors [11].
• In contrast, DHT alone had no effect on CYP19A1 mRNA but synergized with FSH plus E2 to increase CYP19A1 mRNA, probably due to induction of FSHR by DHT [11].
• In contrast, CYP19A1 mRNA was induced by all doses of E2 but only high doses of T and DHT [11].
• However, the specific androgen receptor antagonist bicalutamide did not block E2 or T effects on CYP19A1 but did block T and DHT stimulation of FSHR [11].
• We were able to demonstrate aromatase activity by assaying the incorporation of tritium into [3H] water from [1 beta-3H]androstenedione [14].

Regulatory relationships of CYP19

• Treatment with HGF reduced basal and FSH-stimulated levels of aromatase activity in bovine and rat granulosa cells [15].
• Insulin and IGF-I are necessary for FSH-induced cytochrome P450 aromatase but not cytochrome P450 side-chain cleavage gene expression in oestrogenic bovine granulosa cells in vitro [16].

Other interactions of CYP19

• Similarly, varying treatment duration (1-5 days) showed that FSHR was increased by T and DHT and CYP19A1 mRNA increased by E2 and T at all times [11].
• Temporal relationships between FSH receptor, type 1 insulin-like growth factor receptor, and aromatase expression during FSH-induced differentiation of bovine granulosa cells maintained in serum-free culture [17].
• Changes in messenger ribonucleic acid encoding luteinizing hormone receptor, cytochrome P450-side chain cleavage, and aromatase are associated with recruitment and selection of bovine ovarian follicles [12].
• Cyp19 transcript variants, derived from different promoters, as well as transcripts of Hsd3b, Cyp11A1, and Cyp17, encoding the steroidogenic enzymes P450arom, 3beta-HSD, P450SCC, and P450C17, respectively, were quantified by newly developed real-time PCR assays [18].
• Cyp19 transcript were found at high concentration in the placenta and at a very low concentration in corpus luteum [18].

Analytical, diagnostic and therapeutic context of CYP19

• To establish a high resolution physical map of the entire CYP19 locus, fluorescence in situ hybridization to extended bovine genomic DNA fibers (fiber FISH) was performed [7].
• By in situ hybridization, mRNAs for LH and FSH receptors, P450 aromatase and P450 17alpha-hydroxylase (17alpha-OH) were localized in frozen sections from each follicle [19].
• To determine whether the E1A or E1B sequence was common to aromatase mRNAs in other steroidogenic preimplantation embryos, aromatase cDNA clones spanning exons 1-3 were isolated from equine embryos by a combination of RT-PCR and 5'-rapid amplification of cDNA ends [20].
• Immunocytochemistry and aromatase activity assay indicated the presence of androgen and estrogen receptors as well as aromatase in MNs but not in GCL [21].
• FSH was measured before and after IEF by a highly specific time-resolved immunofluorimetric assay (IFMA), by a radioligand receptor assay (RRA) employing a preparation of calf testis FSH receptors, and by the in vitro bioassay based on FSH-dependent aromatase stimulation in immature rat Sertoli cells [22].

References