API

Relationship: 43

Title

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Decrease, Aromatase (Cyp19a1) leads to Reduction, 17beta-estradiol synthesis by ovarian granulosa cells

Upstream event

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Decrease, Aromatase (Cyp19a1)

Downstream event

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Reduction, 17beta-estradiol synthesis by ovarian granulosa cells

Key Event Relationship Overview

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AOPs Referencing Relationship

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Taxonomic Applicability

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Sex Applicability

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Life Stage Applicability

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How Does This Key Event Relationship Work

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Aromatase is the cytochrome P450 enzyme complex responsible for the conversion of androgens to estrogens during steroidogenesis [rewiewed i.a. in (Simpson et al., 1994)] which is a key reaction in the sex differentiation in vertebrates. Alterations in the amount of aromatase present or in the catalytic activity of the enzyme will alter the levels of estrogens in tissues and dramatically disrupt estrogen hormone action. From one hand inhibition of aromatase alters the catalytic activity of the enzyme and results in a rapid decrease in the levels of estrogens. Suppression or induction of the aromatase protein levels also can dramatically influence the subsequent levels of estrogens in tissues and affect hormone action. Environmental agents, toxicants, and various natural products can act via aromatase inhibition and/or alteration in aromatase protein levels to result in altered levels of estrogen and function as endocrine disruptors.

Weight of Evidence

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Biological Plausibility

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Empirical Support for Linkage

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Uncertainties or Inconsistencies

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Quantitative Understanding of the Linkage

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Evidence Supporting Taxonomic Applicability

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References

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