Question 1

What is the Meaning of AKR1C3?

Accepted Answer

AKR1C3, or Aldo-Keto Reductase Family 1 Member C3, is an enzyme within the aldo-keto reductase superfamily. It catalyzes the reduction of various carbonyl compounds, including key steroid hormones, directly impacting metabolic pathways.

Question 2

What is the Context of AKR1C3?

Accepted Answer

This enzyme operates within the steroid hormone metabolism pathway. It plays a pivotal role in the biosynthesis and inactivation of critical sex steroids like androgens, estrogens, and progestins, alongside glucocorticoids. AKR1C3 is present in diverse tissues, including prostate, breast, adrenal glands, and liver, where its activity directly impacts local hormone concentrations.

Question 3

What is the Significance of AKR1C3?

Accepted Answer

AKR1C3 holds considerable clinical importance, particularly in hormone-sensitive cancers like prostate and breast cancer, where its overexpression can contribute to therapeutic resistance. Its activity influences conditions related to androgen excess or deficiency, impacting patient symptoms and treatment effectiveness. Understanding this enzyme is crucial for addressing specific hormonal imbalances.

Question 4

What is the Mechanism of AKR1C3?

Accepted Answer

Functioning as a 3-keto steroid reductase, AKR1C3 converts active steroid hormones like androstenedione to testosterone or progesterone to 20α-dihydroprogesterone, modulating their biological activity. It also acts as a 17β-hydroxysteroid dehydrogenase (17β-HSD type 5), reducing 4-androstene-3,17-dione to testosterone and estrone to estradiol. This contributes to local potent sex hormone production, directly shaping the steroid environment within target tissues.

Question 5

What is the Application of AKR1C3?

Accepted Answer

AKR1C3 is a compelling target for therapeutic interventions in hormone-dependent cancers, as its inhibition can diminish growth-promoting steroid production within tumor cells. Research actively explores its potential as a reliable biomarker for disease progression or to predict treatment response. Understanding its function assists in developing precise strategies for managing hormonal imbalances and associated pathologies.

Question 6

What is the Metric of AKR1C3?

Accepted Answer

Expression levels or enzymatic activity of AKR1C3 can be assessed in tissue biopsies utilizing immunohistochemistry or quantitative polymerase chain reaction. In vitro enzyme activity assays can further quantify its metabolic function. While direct measurement of the enzyme in blood is not standard clinical practice, circulating levels of its steroid substrates and products may offer indirect insights into its systemic impact.

Question 7

What is the Risk of AKR1C3?

Accepted Answer

Dysregulation of AKR1C3 activity poses a significant risk, contributing to disease progression in hormone-dependent cancers by altering local steroid hormone concentrations. Therapeutic inhibition of AKR1C3 may lead to off-target effects on other metabolic pathways or induce unintended hormonal imbalances, necessitating meticulous clinical monitoring. Overexpression can result in increased local production of potent steroids, potentially exacerbating conditions like benign prostatic hyperplasia or polycystic ovary syndrome.

AKR1C3

Meaning

Context

Significance

Mechanism

Application

Metric

Risk

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