Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In cattle, a dramatic increase in plasma estradiol occurs during the short 2- to 3-day follicular phase. The objective of this study was to investigate the molecular mechanisms that mediate this critical change, specifically whether increases in the steroidogenic ability of granulosa and thecal cells of the preovulatory follicle are associated with increases in the levels of messenger RNA (mRNA) for steroidogenic enzymes. Luteolysis and a follicular phase were induced cycling Holstein heifers (n=15) by injection of a luteolytic dose of prostaglandin F2 alpha (PGF 2 alpha) on day 6 or 7 of the estrous cycle (day 0 = estrus), and preovulatory follicles were obtained at three stages of differentiation (0, 12, or 24 h post-PGF2 alpha treatment). To assess developmental changes in steroidogenesis in vivo, estradiol and androstenedione were measured in follicular fluid and in culture medium after a 3-h incubation of granulosa and thecal cells in defined medium with or without gonadotropins. To determine whether changes in mRNA for steroidogenic enzymes are associated with changes in follicular steroidogenesis, levels of mRNA for cytochrome P450 side-chain cleavage (P450scc), 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), cytochrome P450 17 alpha-hydroxylase, and cytochrome P450 aromatase (P450arom) were measured in thecal and granulosa cells using ribonuclease protection assays. Concentrations of estradiol in follicular fluid were relatively high at time zero, increased significantly by 12 h, and increased further by 24 h post-PGF2 alpha treatment. However, the aromatizing activity of granulosa cells was high at the time of PGF2 alpha injection and did not increase significantly during the first 24 h after the initiation of luteolysis. The aromatizing activity of granulosa cells was reflected in levels of mRNA for P450arom, which was relatively abundant in granulosa cells obtained before luteolysis and did not increase further during the first 24 h of the follicular phase. Concentrations of androstenedione were virtually undetectable in follicular fluid at time zero and had increased dramatically by 12 and 24 h post-PGF2 alpha treatment. Similarly, thecal cells isolated at 24 h secreted 3-fold more androstenedione than cells isolated at the time of PGF2 alpha injection. Androstenedione production by thecal cells in response to LH was also markedly higher at 12 and 24 h than at the time of PGF2 alpha injection. Likewise; levels of mRNA for P450 17 alpha-hydroxylase increased significantly by 12 h post-PGF2 alpha treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differentiation of bovine preovulatory follicles during the follicular phase is associated with increases in messenger ribonucleic acid for cytochrome P450 side-chain cleavage, 3 beta-hydroxysteroid dehydrogenase, and P450 17 alpha-hydroxylase, but not P450 aromatase. 758 47

Brain aromatase plays an important role in the regulation of adult reproductive behavior in male rodents. This report focuses on recent experiments from our laboratory that examined the distribution and regulation of aromatase mRNA in the rat brain. Aromatase mRNA was measured by a highly sensitive ribonuclease protection assay using a 32P-labeled antisense RNA probe that was complimentary to the 5' coding region of rat aromatase mRNA. This probe protects two RNA fragments in rat brain tissue: a 430-nt length fragment and a shorter 300-nt fragment. The presence of the 300-nt RNA fragment is not associated with enzyme activity in the rat brain and appears to represent an alternative brain-specific aromatase transcript whose function, if any, is unknown. In contrast, the 430-nt RNA fragment represents mRNA, which is thought to encode functional aromatase enzyme because its levels are correlated with aromatase activity concentrations in preoptic area, hypothalamus, amygdala, and ovary. Aromatase activity and mRNA levels in the preoptic area and hypothalamus decreased by 7 days after castration and were maintained at intact levels by treatment with testosterone and dihyhdrotestosterone, but not with estradiol. In contrast, neither aromatase activity nor mRNA levels in the amygdala are affected by castration or hormone replacement. In addition, sex differences in the regulation of aromatase mRNA were apparent in both the preoptic area and hypothalamus. These results demonstrate that androgens regulate the transcription or stability of aromatase mRNA in specific brain areas. Moreover, they suggest that gender differences in androgen responsiveness play an important role in regulating gene expression in the adult rat brain.
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PMID:Regulation of aromatase gene expression in the adult rat brain. 937 Jan 99

Increased extraglandular aromatization has been reported as the cause of familial gynecomastia. We studied a kindred with aromatase excess inherited in an autosomal dominant manner, in which affected males had heterosexual precocity and/or gynecomastia, and affected females had isosexual precocity and/or macromastia. The propositus was a 9-yr-old boy with gynecomastia. His 7.5-yr-old sister had precocious puberty, and their father and paternal grandmother had peripubertal gynecomastia and macromastia, respectively. Serum concentrations of gonadal and adrenal steroid hormones were determined before and after the administration of corticotropin and/or hCG. Aromatase activity was determined by [3H]delta4-androstenedione to [3H]estrone conversion by cultured skin fibroblasts and/or Epstein-Barr virus-transformed lymphocytes and was detected by immunohistochemistry and/or Western analysis. Linkage was examined with a polymorphism of the aromatase (P450arom) gene. The P450arom messenger ribonucleic acid was analyzed by rapid amplification of complementary DNA (cDNA) ends, ribonuclease protection assay, and RT-PCR. hCG testing demonstrated a high rate of conversion of delta4-androstenedione to estrone and of testosterone to estradiol in the propositus and his father. Treatment of the propositus and his sister was initiated with an aromatase inhibitor (testolactone) and a GnRH analog, which successfully delayed skeletal and pubertal development in both children. Markedly increased aromatase activity was found in the patients' fibroblasts and Epstein-Barr virus-transformed lymphocytes. The P450arom polymorphism segregated with the disease in the family. A new 5'-splice variant was present in the patients' P450arom messenger ribonucleic acid, thus identifying yet another first exon of this gene, which appears to be aberrantly expressed in this family. In conclusion, a family with the aromatase excess syndrome is described, in which the condition was inherited in an autosomal dominant manner, led to feminizing manifestations in both sexes, and was associated with the aberrant utilization of a novel transcript of the P450arom gene.
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PMID:The aromatase excess syndrome is associated with feminization of both sexes and autosomal dominant transmission of aberrant P450 aromatase gene transcription. 954 66

To understand the role of estrogen in testicular and epididymal function of rhesus monkeys, we measured steroids in the spermatic and peripheral venus circulation and aromatase activity and its mRNA in testis and epididymis. Testosterone, estradiol-17beta, and estrone, but not androstenedione, were elevated in the spermatic vein serum compared to the peripheral circulation. Aromatase activity in testis and in caput epididymis (259+/-16 [SEM] vs 274+/-47 fmol of 3H2O/mg of protein/h [n = 10], respectively) was significantly higher (p < 0.01) than in corpus and cauda (124+/-28 and 113+/-33 fmol of 3H2O/mg of protein/h [n = 10], respectively). In the ribonuclease protection assay, two P450arom mRNA transcripts were identified in testis and epididymis. One corresponded with the aromatase full-length transcript and the other was a truncated isoform. The latter was significantly more abundant than the former (p < 0.01). Our results demonstrate that the monkey testis and, to a lesser extent, the epididymis can aromatize androgens. However, in the epididymis, like in some areas of the brain, there was a discrepancy between the aromatase activity and the mRNA. The fact that P450arom mRNA and aromatase activity do not correlate in the epididymis may indicate that aromatase activity is not strictly regulated at the level of RNA expression and that other mechanisms for this regulation should be considered.
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PMID:Cytochrome P450 aromatase in testis and epididymis of male rhesus monkeys. 1182 22