Diverse function of aromatase and the N-terminal sequence deleted form

Osawa, Yoshio; Higashiyama, Tetsuya; Toma, Yoshiro; Yarborough, Carol

doi:10.1016/s0960-0760(97)80002-7

Cited by 25 publications

(5 citation statements)

References 21 publications

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“…Estrogens are derived from androgens, through a multi-step process catalyzed by the enzyme aromatase (Boon et al, 2010;Osawa et al, 1997). Within the brain, the hypothalamus is one of the major sites of estrogen synthesis (Biegon et al, 2010;Coumailleau and Kah, 2014;Foidart et al, 1995a;Menuet et al, 2003;Roselli et al, 1998;Roselli and Resko, 2001;Sasano et al, 1998;Stanić et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Site-specific effects of aromatase inhibition on the activation of male sexual behavior in male Japanese quail (Coturnix japonica)

Bournonville

Vandries

Ball

et al. 2019

Hormones and Behavior

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Aromatization within the medial preoptic nucleus (POM) is essential for the expression of male copulatory behavior in Japanese quail. However, several nuclei within the social behavior network (SBN) also express aromatase. Whether aromatase in these loci participates in the behavioral activation is not known. Castrated male Japanese quail were implanted with 2 subcutaneous Silastic capsules filled with crystalline testosterone and with bilateral stereotaxic implants filled with the aromatase inhibitor Vorozole targeting the POM, the bed nucleus of the stria terminalis (BST) or the ventromedial nucleus of the hypothalamus (VMN). Control animals were implanted with testosterone and empty bilateral stereotaxic implants. Starting 2 days after the surgery, subjects were tested for the expression of consummatory sexual behavior (CSB) every other day for a total of 10 tests. They were also tested once for appetitive sexual behavior (ASB) as measured by the rhythmic cloacal sphincter movements displayed in response to the visual presentation of a female. CSB was drastically reduced when the Vorozole implants were localized in the POM, but not in the BST nor in the VMN. Birds with implants in the BST showed a longer latency to show CSB in the first 6 tests than controls, suggesting a role of the BST in the acquisition of the full copulatory ability. ASB was not significantly affected by aromatase blockade in any region. These data confirm the key role played by the POM in the control of male sexual behavior and suggest a minor role for aromatization in the BST or VMN.

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Section: Introductionmentioning

confidence: 99%

Site-specific effects of aromatase inhibition on the activation of male sexual behavior in male Japanese quail (Coturnix japonica)

Bournonville

Vandries

Ball

et al. 2019

Hormones and Behavior

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“…Aromatase has been implicated in the metabolism and, specifically, the demethylation of a number of drugs in vitro, including methadone, 18 buprenorphine, 31 and cocaine, 32 but the role that this enzyme plays in the metabolism of xenobiotic medications in humans has not been directly examined before in a clinical study. The clinical trial reported here examined the Data are presented as mean T SD (n = 15).…”

Section: Discussionmentioning

confidence: 99%

Reduced Methadone Clearance During Aromatase Inhibition

Thong²,

Flockhart³

2012

Journal of Clinical Psychopharmacology

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Methadone is increasingly used in pain management and is a cornerstone in the treatment of opiate withdrawal. It is subject to highly variable clearance among patients. The complete metabolic disposition of methadone is likely to involve a number of enzymes, including specifically CYP2B6. Previous studies in vitro suggest that metabolism by aromatase may also contribute. Single-dose methadone pharmacokinetics (2 mg, intravenous) were studied in 15 healthy postmenopausal women in the presence and absence of a potent aromatase inhibitor, letrozole. A sequential design was used, involving a control period followed by treatment with letrozole (2.5 mg/d, 11 days), in which each subject served as her own control. On average, letrozole treatment reduced methadone systemic clearance by 22% (P = 0.001), increased methadone AUC by 23% (P = 0.007), and increased elimination half-life by 21% (P = 0.042). The plasma parent-to-metabolite ratio also increased (P = 0.009), and there was a linear relationship (R2 = 0.74) between change in this plasma ratio and change in methadone AUC0-∞. In contrast, there was no such association with change in apparent urinary methadone clearance. Letrozole did not change methadone distribution half-life or its volume of distribution. Overall, these data demonstrate a significant decrease in methadone clearance during coadministration of letrozole, consistent with decreased metabolism brought about by aromatase inhibition. An involvement of aromatase in the disposition of methadone may help explain the difficulty in methadone dosing and suggests a broader role for this catalyst of endogenous steroid metabolism in xenobiotic drug disposition.

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“…Osawa et al have reported that substrate molecules are presumed to bind to the active site of aromatase through two conformations, such as ␤-side up (considered "normal") and ␣-side up (upside down), or to have the opportunity and space to rotate around the binding site [9]. In the ␤-side up binding position of estradiol, the C-2 position comes close to the heme.…”

Section: Discussionmentioning

confidence: 99%

“…Osawa and co-workers have recently reported that the natural estrogen, which has been considered to be the final product of the aromatase reactions, serves as a substrate for aromatase, yielding catechol estrogen, 2-hydroxyestrogen, as well as 6␣-hydroxyestrogen ( Fig. 1) [7][8][9]. Kinetic analysis of the estrogen 2-and 6␣-hydroxylations and androgen aromatization shows competitive catalysis of both sex steroids by the same catalytic site where androgen has a higher affinity than estrogen (K m : ca.…”

Section: Introductionmentioning

confidence: 99%