Multiple functions of aromatase and the active site structure; aromatase is the placental estrogen 2-hydroxylase

Osawa, Yoshio; Higashiyama, Tetsuya; Shimizu, Yukiko; Yarborough, Carol

doi:10.1016/0960-0760(93)90252-r

Cited by 99 publications

(57 citation statements)

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“…by Osawa et al, when the purified and reconstituted aromatase was subjected to immunosuppression by MAb3-2C2, the inhibition pattern of estradiol 2-hydroxylase activity was almost identical to that of aromatase activity, but rat liver microsomal 2-hydroxylase activity was not suppressed by MAb3-2C2 [8]. In our results with placental microsomes obtained from PIH, estrogen 2-hydroxylase activity was not suppressed completely by MAb3-2C2, but aromatase activity was strongly immunosuppressed by the same dose of MAb3-2C2.…”

Section: Discussionmentioning

confidence: 99%

“…But estrogen 2-hydroxylation by human placental microsomes is believed to also be catalyzed by a distinct cytochrome P450 enzyme [7]. Recently, the capacity of estrogen 2-hydroxylase activity in the human placental aromatase has been described [8]. Osawa et al [8], with the purified and reconstituted placental aromatase P450, showed evidence that human placental estrogen 2-hydroxylation and aromatization are catalyzed by the same human placental aromatase P450.…”

mentioning

confidence: 99%

“…A modification of the procedure of Dannan et al [7] based on the tritiated water method was used to determine estrogen 2-hydroxylase activity as previously reported [8]. Human placental microsomes (0.5 mg protein) were incubated for 20 min at 37 °C with [2-3H]estradiol (1.5 x 105 dpm 3H/ ,ug, 5 pM) as substrate in the presence of NAD-PH (0.75 mM) in a total volume of 1.0 ml of 0.1 M phosphate buffer (pH 7.6).…”

Section: -Hydroxylase Assaymentioning

confidence: 99%

“…Recently, the capacity of estrogen 2-hydroxylase activity in the human placental aromatase has been described [8]. Osawa et al [8], with the purified and reconstituted placental aromatase P450, showed evidence that human placental estrogen 2-hydroxylation and aromatization are catalyzed by the same human placental aromatase P450. They also confirmed that both activities were exhibited in Chinese hamster ovarian cells transfected with human placental aromatase cDNA, pH /3-Aro.…”

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confidence: 99%

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Aromatase and Estrogen 2-Hydroxylase Activities of Human Placental Microsomes in Pregnancy-Induced Hypertension.

et al. 1996

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Abstract. 2-Hydroxylationis one of the major metabolic pathways of estrogens and is believed to be catalyzed by a form of cytochrome P450. Recently it has been reported that estrogen 2-hydroxylase activity in human placenta is catalyzed by aromatase.Some investigators suggested the effect of catechol estrogen on human placental steroidogenesis which may be related to pregnancy-induced hypertension (PIH) through the inhibition of catechol-0-methyltransferase (COMT) activity. In order to better understand the interrelationship between placental aromatase and estrogen 2-hydroxylase activities in PIH patients, both activities were evaluated in the PIH placentas.Human placental microsomes obtained from PIH patients were incubated with [1/3-3H]androstenedione or [2-3H]estradiol in the presence of NADPH. Aromatase and estrogen 2-hydroxylase activities were assessed by the tritium water method. The immunosuppression patterns of both activities due to monoclonal antiaromatase cytochrome P450 antibody (MAb3-2C2) were studied. Estrogen 2-hydroxylase activity was significantly higher in PIH placentas (4.7 ± 0.9 pmol/min/mg protein, n=7) than in normal placentas (3.0 ± 0.7 pmol/min/mg protein, n=7). When the PIH placental microsomes were subjected to immunosuppression by 1 to 100 µg IgG of MAb3-2C2, estrogen 2-hydroxylase activity was suppressed by 94 to 65% whereas aromatase activity was strongly suppressed by 72 to 17%, respectively. From our results of high estrogen 2-hydroxylase activity in PIH placentas, it is assumed that there is a different estrogen catalyzing mechanism in PIH placentas.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Section: -Hydroxylase Assaymentioning

confidence: 99%

mentioning

confidence: 99%

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Aromatase and Estrogen 2-Hydroxylase Activities of Human Placental Microsomes in Pregnancy-Induced Hypertension.

et al. 1996

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“…In addition, aromatase itself appears to catalyze in the placenta both the conversion of testosterone into E 2 and the 2-hydroxylation of estrogens into catecholestrogens. The switch between these two enzymatic activities (catalyzed by the same protein) would dependent on the availability of the substrates and the local pH [189]. If this scenario turns out to be true in the brain, this mechanism would provide a very effective way to rapidly control local concentrations of neuro-active estrogens.…”

Section: What Terminates Estrogen Action In the Brain?mentioning

confidence: 99%

Functional significance of the rapid regulation of brain estrogen action: Where do the estrogens come from?

2006

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Estrogens exert a wide variety of actions on reproductive and non-reproductive functions. These effects are mediated by slow and long lasting genomic as well as rapid and transient non-genomic mechanisms. Besides the host of studies demonstrating the role of genomic actions at the physiological and behavioral level, mounting evidence highlights the functional significance of non-genomic effects. However, the source of the rapid changes in estrogen availability that are necessary to sustain their fast actions is rarely questioned. For example, the rise of plasma estrogens at pro-estrus that represents one of the fastest documented changes in plasma estrogen concentration appears too slow to explain these actions. Alternatively, estrogen can be synthesized in the brain by the enzyme aromatase providing a source of locally high concentrations of the steroid. Furthermore, recent studies demonstrate that brain aromatase can be rapidly modulated by afferent inputs, including glutamatergic afferents. A role for rapid changes in estrogen production in the central nervous system is supported by experiments showing that acute aromatase inhibition affects nociception as well as male sexual behavior and that preoptic aromatase activity is rapidly (within min) modulated following mating. Such mechanisms thus fulfill the gap existing between the fast actions of estrogen and their mode of production and open new avenues for the understanding of estrogenic effects on the brain.

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Anatomical relationships between aromatase and tyrosine hydroxylase in the quail brain: Double-label immunocytochemical studies

et al. 1998

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The activation of male sexual behavior in Japanese quail (Coturnix japonica) requires the transformation of testosterone to 17beta-estradiol by the enzyme aromatase (estrogen synthetase). There are prominent sex differences in aromatase activity that may be regulated in part by sex differences in catecholaminergic activity. In this study, we investigate, with double-label immunocytochemistry methods, the anatomical relationship between the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH) and aromatase (ARO) in the quail brain. The immunoreactivity observed for each antigen generally matched the previously described distribution. One exception is the observation that cells weakly labeled for aromatase were found widely distributed throughout the telencephalon. The presence of telencephalic aromatase was confirmed independently by radioenzymatic assays. There was an extensive overlap between the distribution of the two antigens in many brain areas. In all densely labeled aromatase-immunoreactive (ARO-ir) cell groups, including the preoptic medial nucleus, nucleus of the stria terminalis, mediobasal hypothalamus, and paleostriatum ventrale, ARO-ir cells were found in close association with TH-ir fibers. These TH-ir fibers often converged on an ARO-ir cell, and one or more TH-ir punctate structure(s) were found in close contact with nearly every densely labeled ARO-ir cell. In the telencephalon (mostly the neostriatum), all TH-ir fibers were found to be part of fiber groups that surrounded weakly immunoreactive aromatase cells. The few cells exhibiting an intracellular colocalization were detected in the anteroventral periventricular nucleus. These results are consistent with the hypothesis that catecholaminergic inputs regulate brain aromatase.

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Multiple functions of aromatase and the active site structure; aromatase is the placental estrogen 2-hydroxylase

Cited by 99 publications

References 15 publications

Aromatase and Estrogen 2-Hydroxylase Activities of Human Placental Microsomes in Pregnancy-Induced Hypertension.

Aromatase and Estrogen 2-Hydroxylase Activities of Human Placental Microsomes in Pregnancy-Induced Hypertension.

Functional significance of the rapid regulation of brain estrogen action: Where do the estrogens come from?

Anatomical relationships between aromatase and tyrosine hydroxylase in the quail brain: Double-label immunocytochemical studies

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