Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aromatase cytochrome P-450 (P-450AROM) cDNA, which was identified by homologies in the DNA and in the deduced amino acid sequences with human P-450AROM cDNA, was isolated from a brain cDNA library of Japanese quail, demonstrating the presence of RNA transcripts of P-450AROM in the quail brain. To determine trace amounts of P-450AROM mRNA in the brain and to examine the effects of testosterone on its expression, a quantitative PCR method of RNA transcripts was developed. Brain total RNA was subjected to reverse transcription reaction and then quantitated by PCR from cDNA with a fluorescent dye-labeled primer. The quantity of P-450AROM mRNA was calculated by using an internal standard of modified P-450AROM (m-P-450AROM) RNA. The brain P-450AROM was primarily transcribed in the hypothalamus area (1.15 +/- 0.14 amol/micrograms of RNA) and traces of transcripts only were detected in the cerebellum (0.038 +/- 0.005 amol/micrograms of RNA). The P-450AROM mRNA in the hypothalamus of castrated quail was low (0.270 +/- 0.078 amol/micrograms of RNA) and increased 4- to 5-fold following treatment with testosterone. These results demonstrate, for the first time, that the increase in P-450AROM activity that is observed in the brain following treatment with testosterone results from a pretranslational regulation of the P-450AROM by androgens.
Brain Res Mol Brain Res 1992 Sep
PMID:Regulation of aromatase cytochrome P-450 (estrogen synthetase) transcripts in the quail brain by testosterone. 133 67

Aromatase cytochrome P-450 (P-450AROM) enzyme activity catalyzes the conversion of androgens to estrogens in specific brain areas. During development local estrogen formation is thought to influence the sexual differentiation of neural structures (i.e. increase neurite growth and establish neural circuitry) and modulate reproductive functions. This study was undertaken to investigate the ontogeny of the (P-450AROM) enzyme and its messenger RNA (mRNA) in medial basal hypothalamic (MBH) and preoptic area (POA) tissue during late fetal and perinatal development of the rat. Aromatase activity in the MBH-POA was negligible before gestational day (GD) 16 (< 0.1 pmol/h/mg protein), increased over 10-fold at GD 17 and continued to increase (over 5-fold) to peak levels at GD 19 (> 5.0 pmol/h/mg protein), and then declined to low levels at GD 22 and 2 days post-birth (approximately 1 pmol/h/mg protein). The profile of P-450AROM mRNA in the MBH-POA tissue was characterized by a predominant 2.7 kilobase (kb) mRNA species, similar in size to the largest functional P-450AROM mRNA observed in adult rat ovarian tissue. At GD 15, the P-450AROM mRNA was undetectable; low but detectable levels were seen at GD 17, the abundance increased at later time points and remained at peak levels on GDs 18 through 20, decreased slightly by GD 22, and then declined further by 2 days post-birth. The developmental increase in P-450AROM mRNA levels correlated with the ascending pattern of enzyme activity before GD 19, but the marked decrease in enzyme activity seen after GD 19 was not accompanied by a corresponding decline in mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1992 Dec
PMID:Brain aromatase cytochrome P-450 messenger RNA levels and enzyme activity during prenatal and perinatal development in the rat. 133 28

We have previously reported the isolation and characterization of the human gene encoding aromatase cytochrome P-450 (P-450AROM). The gene had been demonstrated to span at least 52 kb and contain ten exons, the first of which, exon I.1, is untranslated. Here we report the isolation and characterization of a P-450AROM cDNA from a human placental primer-extended cDNA library which contains a unique 5' sequence. This cDNA has been isolated and sequences used to screen a human placental genomic library for the presence of a unique first exon. The exon (exon I.2) lies 9 kb 5' of the second, ATG-containing exon (exon II) and is spliced onto exon II at the same site as that reported for exon I.1. DNA sequence analysis indicates that exon I.2 has a putative TATA (TAAA) sequence 33 base pairs (bp) upstream from a putative transcription start site and putative CAAT (CATT) binding sequence beginning at 54 bp upstream from this start site. Polymerase chain reaction (PCR) amplification experiments indicate that mRNA containing exon I.2-specific sequences can be demonstrated in tissues of fetal, but not adult, origin. These data have been confirmed by Northern analysis in the placenta. Characterization of this genomic clone containing exons I.2 and II now establishes the P-450AROM gene to be at least 72 kb in length and raises new questions regarding tissue specific and developmental control of aromatase expression in the human.
Mol Cell Endocrinol 1992 Jan
PMID:Alternative promotion of aromatase P-450 expression in the human placenta. 137 68

We examined the changes in P-450AROM mRNA, aromatase enzyme activity and serum estradiol levels (E2) in anestrous, pregnant mare's serum gonadotropin (PMSG)-treated immature, pregnant, and lactating rats to determine if: (a) the various mRNA species encoding P-450AROM in rat ovarian tissue are differentially expressed during different hormonal states, and (b) a positive relationship exists between P-450AROM mRNA and enzymatic activity in rat ovarian tissue and serum estradiol levels from the same animals. Utilizing three different cDNAs encoding rat P-450AROM, levels of P-450AROM mRNA were determined by RNA blot analysis and scanning densitometry. Probe 1, a 5' probe, detects all three P-450AROM mRNA species in rat ovarian tissue (i.e. at 1.7, 2.2 and 2.7 kb). Probe 2 contains an unspliced intronic sequence in place of the heme-binding domain at its 3' terminus and thus the mRNA detected by this probe must encode a nonfunctional aromatase protein. Only the two smaller (i.e. nonfunctional) mRNA species at 1.7 and 2.2 kb are detected by probe 2. Probe 3 contains the heme-binding region and hybridizes to principally the largest mRNA transcript at 2.7 kb (but hybridizes also to a 1.7 kb mRNA transcript). Aromatase enzyme activity was measured by using a saturating concentration of [1 beta-3H]testosterone as substrate in the [3H]water-release assay while serum estradiol levels were determined by radioimmunoassay. In immature rats (IR) or lactating animals (LA) P-450AROM mRNA was not detectable along with low serum estradiol (IR approximately 2.8 pg/ml; LA approximately 0.2 pg/ml) and aromatase activity levels (IR approximately 0.8 pmol/h per mg protein; LA less than 0.5 pmol/h per mg protein). Anestrous animals treated with 5 IU of PMSG resulted in a clear increase (24 h later) in P-450AROM mRNA levels, in concert with a 4-fold increase in serum E2 (approximately 12.5 pg/ml) and aromatase activity (approximately 4.2 pmol/h per mg protein). During pregnancy, all three mRNA species were clearly detectable, but low serum E2 levels (approximately 0.6 pmol/ml) and P-450AROM mRNA abundance were observed at 3 days of gestation (DG). Levels of all three P-450AROM mRNA species increased markedly at 15 and 18 DG; thereafter, the levels declined at 20 DG and further decreased at 22 DG. However, regardless of the probe utilized (probe 1, 2 or 3) in the RNA blot analyses, the mRNA transcripts detected by each probe were expressed in a concerted fashion with respect to abundance and pattern.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Cell Endocrinol 1992 Jun
PMID:Ovarian aromatase cytochrome P-450 mRNA levels correlate with enzyme activity and serum estradiol levels in anestrous, pregnant and lactating rats. 163 17

We have examined the levels of expression of mRNA species encoding cholesterol side-chain cleavage cytochrome P-450 (P-450scc), 17 alpha-hydroxylase cytochrome P-450 (P-450(17 alpha), aromatase cytochrome P-450 (P-450AROM) and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in rat ovaries throughout the oestrous cycle, during pregnancy and in immature animals treated with pregnant mare serum gonadotrophin (PMSG). Total or poly(A)(+)-enriched RNA was prepared from adult rat ovaries throughout the oestrous cycle, from immature rat ovaries 24 and 48 h after treatment and from adult rat ovaries on days 10, 14, 17 and 21 of gestation. Expression of the mRNA species was examined by Northern analysis using specific [32P]cDNA probes. During the oestrous cycle P-450scc mRNA of approximately 1.9 kb was detected at low levels, while 3 beta-HSD mRNA of 1.7 kb was in relatively high abundance throughout the oestrous cycle. While P-450(17) alpha mRNA of 1.9 kb and P-450AROM of 2.7, 2.2 and 1.7 kb were highly abundant during dioestrus, pro-oestrus and oestrus, the levels of these mRNA species decreased markedly to be nearly undetectable during metoestrus. During pregnancy there was considerably more variation in the expression of the mRNA species examined. Expression of P-450scc mRNA was at low, but detectable, levels until day 14, thereafter expression increased to high levels (day 14-21 of gestation). Levels of P-450(17) alpha mRNA on day 10 of gestation were lower than at pro-oestrus during the oestrous cycle and decreased further on days 14 and 17. Expression of 3 beta-HSD was decreased on day 10, but on days 14, 17 and 21 of gestation high mRNA levels were detectable. Ovarian expression of the three P-450AROM species was dramatically increased between days 14 and 17 of pregnancy, but declined by day 21. In immature rats, P-450scc mRNA was detected at low levels in unstimulated animals and increased markedly after treatment with PMSG, while subsequent treatment with human chorionic gonadotrophin (hCG) had a minimal effect on expression. Expression of P-450(17) alpha mRNA was high in unstimulated immature and PMSG-treated rats, but diminished after treatment with hCG. All three P-450AROM mRNA species were undetectable in ovaries from unstimulated immature animals; however, induction of all three was observed in PMSG-treated rats, but this expression decreased to undetectable levels upon subsequent administration of hCG.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Endocrinol 1991 Apr
PMID:Expression of mRNA species encoding steroidogenic enzymes in the rat ovary. 171 Apr 61

The formation of estrogens from C19 steroids is catalyzed by a specific form of cytochrome P450, aromatase cytochrome P450 (P450AROM; the product of the CYP19 gene). Previous studies have demonstrated that aromatase activity in human adipose and ovarian granulosa cells is subject to complex multifactorial regulation and that changes in activity are correlated with changes in the levels of mRNA encoding P450AROM. We have previously isolated the human CYP19 gene. Two unique untranslated first exons (exons I.1 and I.2) have been identified in mRNA specific for P450AROM in human placenta. Although the proportion of transcripts encoding exon I.2 is very small, genomic clones encoding the sequences of both exons I.1 and I.2 have recently been isolated. The corpus luteum of human ovary differs in that promoters I.1 and I.2 are completely inactive. Sequence analysis of the DNA immediately 5' of exon II (which contains the start site of translation) demonstrates the presence of a TATAA sequence beginning 149 basepairs 5' of the ATG initiation codon identified in placental exon II. Using a combination of primer extension and S1 nuclease protection analysis, it appears that the initiation site of ovarian P450AROM transcripts aligns 26 basepairs down-stream of the sequence TATAA. It appears, therefore, that the expression of P450AROM-specific mRNA in corpus luteum is regulated by an additional promoter (promoter II), which is located just 5' of exon II. Consistent with these observations, Northern analysis of poly(A)+ RNA isolated from placenta and corpus luteum demonstrates that the major promoter of placental P450AROM is promoter I.1, while the major promoter in the corpus luteum is promoter II.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1991 Dec
PMID:Tissue-specific promoters regulate aromatase cytochrome P450 gene expression in human ovary and fetal tissues. 172 89

The HPR1 gene has been cloned by complementation of the hyperrecombination phenotype of hpr1-1 strains by using a color assay system. HPR1 is a gene that is in single copy on chromosome IV of Saccharomyces cerevisiae, closely linked to ARO1, and it codes for a putative protein of 752 amino acids (molecular mass, 88 kilodaltons). Computer searches revealed homology (48.8% conserved homology; 24.8% identity) with the S. cerevisiae TOP1 gene in an alpha-helical stretch of 129 amino acids near the carboxy-terminal region of both proteins. The ethyl methanesulfonate-induced hpr1-1 mutation is a single-base change that produces a stop codon at amino acid 559 coding for a protein that lacks the carboxy-terminal TOP1 homologous region. Haploid strains carrying deletions of the HPR1 gene show a slightly reduced mitotic growth rate and extremely high rates of intrachromosomal excision recombination (frequency, 10 to 15%) but have a undetectable effect on rDNA recombination. Double-null mutants hpr1 top1 grow very poorly. We conclude that Hpr1 is a novel eucaryotic protein, mutation of which causes an increase in mitotic intrachromosomal excision recombination, and that it may be functionally related to an activity of the topoisomerase I protein.
Mol Cell Biol 1990 Apr
PMID:HPR1, a novel yeast gene that prevents intrachromosomal excision recombination, shows carboxy-terminal homology to the Saccharomyces cerevisiae TOP1 gene. 218 Dec 75

The effects of FSH to increase the activity of aromatase, as well as the synthesis of the components of the aromatase enzyme complex, have been studied in human ovarian granulosa cells obtained from women undergoing oocyte retrieval. FSH increased aromatase activity, as well as the synthesis of aromatase cytochrome P-450 (P-450AROM) in a time-dependent fashion, whereas in the absence of FSH, both activity and synthesis declined with duration of culture. The effect of FSH was mimicked by forskolin, an activator of adenylate cyclase. FSH also increased the synthesis of NADPH-cytochrome P-450 reductase, but to a relatively modest extent. The levels of hybridizable mRNA species encoding cytochrome P-450AROM of lengths 3.0, 2.4, and 1.6 kilobases were also increased with FSH treatment. It is concluded that the regulation of aromatase activity by FSH in human granulosa cells is mediated primarily by changes in the synthesis of cytochrome P-450AROM, that this action of FSH is mediated by cAMP, and that the changes in cytochrome P-450AROM synthesis are the consequences of changes in the levels of mRNA encoding this enzyme.
Mol Endocrinol 1987 Jul
PMID:Regulation by follicle-stimulating hormone of the synthesis of aromatase cytochrome P-450 in human granulosa cells. 315 62

The effects of growth factors to regulate the activity of aromatase, as well as the synthesis of aromatase cytochrome P-450 (P-450AROM) have been studied in human ovarian granulosa cells obtained from women undergoing oocyte retrieval. Insulin-like growth factor I (IGF-I) increased aromatase activity as well as the synthesis of P-450AROM, in a concentration-dependent fashion. The levels of hybridizable mRNA species encoding cytochrome P-450AROM were also increased with IGF-I treatment. By contrast, epidermal growth factor (EGF) had no effect on these parameters when added alone, but markedly inhibited the action of follicle-stimulating hormone (FSH) to stimulate aromatase activity, and the synthesis of cytochrome P-450AROM, as well as its ability to increase the levels of mRNA encoding the enzyme. It is concluded that these growth factors have opposite effects on aromatase activity, and that these actions reflect, in part, changes in the synthesis of cytochrome P-450AROM, which in turn are the consequence of changes in the levels of mRNA encoding this enzyme.
Mol Cell Endocrinol 1988 Sep
PMID:Effects of epidermal growth factor and insulin-like growth factor I on the levels of mRNA encoding aromatase cytochrome P-450 of human ovarian granulosa cells. 326 56

Two cDNA inserts complementary to mRNA encoding aromatase cytochrome P-450 (P-450AROM) have been isolated and characterized by restriction mapping and sequencing. The overlapping sequence encoded by these inserts is identical, and a putative heme-binding region has been identified. In addition, the open reading frame contains the sequences of all four cysteine-containing tryptic peptides isolated by Chen et al. (1986) from purified cytochrome P-450AROM. The inserts differ in the use of alternative poly A-addition signals, which is consistent with the presence of two major species of mRNA in human placenta, of 3.0 and 2.4 kb, which hybridize to these inserts. The identity of sequence between the two inserts and the likely presence of alternative poly A-addition signals, is suggestive that only one form of cytochrome P-450AROM is encoded by these mRNA species.
Mol Cell Endocrinol 1987 Aug
PMID:Sequencing of cDNA inserts encoding aromatase cytochrome P-450 (P-450AROM). 365 7


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