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Last update 23 Jan 2025

17β-HSD3

Last update 23 Jan 2025

Basic Info

Synonyms

17-beta-HSD 3, 17-beta-hydroxysteroid dehydrogenase type 3, EDH17B3

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Introduction

Catalyzes the conversion of 17-oxosteroids to 17beta-hydroxysteroids (PubMed:8075637, PubMed:16216911, PubMed:27927697, PubMed:26545797). Favors the reduction of androstenedione to testosterone (PubMed:16216911, PubMed:27927697, PubMed:26545797). Testosterone is the key androgen driving male development and function (PubMed:8075637). Uses NADPH while the two other EDH17B enzymes use NADH (PubMed:26545797, PubMed:8075637, PubMed:16216911). Androgens such as epiandrosterone, dehydroepiandrosterone, androsterone and androstanedione are accepted as substrates and reduced at C-17 (PubMed:16216911). Can reduce 11-ketoandrostenedione as well as 11beta-hydroxyandrostenedione at C-17 to the respective testosterone forms (PubMed:16216911, PubMed:27927697).

Drugs associated with 17β-HSD3

STX2171

Target

17β-HSD3

Mechanism

17β-HSD3 inhibitors

Active Org.

Sterix Ltd.

Originator Org.

Sterix Ltd.

Active Indication

Hormone-dependent prostate cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

STX2624

Target

17β-HSD3

Mechanism

17β-HSD3 inhibitors

Active Org.

Sterix Ltd.

Originator Org.

Sterix Ltd.

Active Indication

Hormone-dependent prostate cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

STX1383

Target

17β-HSD3

Mechanism

17β-HSD3 inhibitors

Active Org.

Sterix Ltd.

Originator Org.

Sterix Ltd.

Active Indication

Hormone-dependent prostate cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with 17β-HSD3

100 Translational Medicine associated with 17β-HSD3

0 Patents (Medical) associated with 17β-HSD3

1,119

Literatures (Medical) associated with 17β-HSD3

01 Feb 2025·Fish Physiology and Biochemistry

Comparative transcriptome analysis identified genes involved in testicular development in Takifugu rubripes

Article

Author: Liu, Qi ; Tian, Yushun ; Wang, Xiuli ; Yan, Hongwei ; Li, Meiyuan ; Wang, Liu ; Chen, Jinfeng ; Wang, Chenqi ; Hu, Mingtao ; Liang, Xinyan

To identify candidate genes and pathways involved in testicular development in Takifugu rubripes, a comparative transcription analysis was conducted across the various developmental stages of the testis (stages II to V). A total of 9520 differentially expressed genes (DEGs) were identified among the different stages, and they were significantly clustered into six clusters (P < 0.05). One thousand four hundred eleven DEGs such as gndf, wnt1, and cyp17b1 were found to be decreased from stage II to V. In contrast, 994 DEGs such as fn1, ift81, and cdc25a were found to be increased from stage II to V. Six thousand three hundred eighteen DEGs (e.g., dmrt1, sdk2, and chrna1) were identified as being expressed at similar levels at stages II and III. However, they were subsequently found to be decreased from stage III to IV. Four hundred one DEGs exhibited a significant upregulation trend from stage II to III. These genes were expressed at similar levels in stages III, IV, and V, including chrnd, wnt4a, and cyp7a1. The highest expression levels of 200 DEGs (e.g., ccnb2, cdk1, and sycp2) were observed in stage IV, while 196 DEGs (e.g., chmp1b, hsd17b3, and zp3) exhibited the highest expression level in stage III. Those DEGs were mainly enriched in the pathways (e.g., neuroactive ligand-receptor interaction, cell adhesion molecules, and calcium signaling pathways) associated with testicular development. Quantitative polymerase chain reaction of eight randomly selected genes validated the RNA sequencing results. This study may provide new insights into the molecular regulatory mechanisms governing testicular development and spermatogenesis in T. rubripes.

06 Jan 2025·European Journal of Endocrinology

Gonadal function and pathology in 17beta-HSD 3 and 5alpha-reductase deficiency

Article

Author: Cools, Martine ; Bryce, Jillian ; Holterhus, Paul-Martin ; Looijenga, Leendert H J ; Oosterhuis, J Wolter ; Ellaithi, Mona ; Lucas-Herald, Angela K ; Ahmed, S Faisal ; Brüggenwirth, Hennie T ; Boogers, Lidewij S ; Stancampiano, Marianna Rita ; Hiort, Olaf ; Hersmus, Remko ; van Bever, Yolande ; Baronio, Federico ; Wolffenbuttel, Katja P ; Güran, Tülay ; Hannema, Sabine E ; Niedziela, Marek ; Globa, Evgenia ; Tosun, Buşra G ; MсElreavey, Kenneth

AbstractObjective17β-Hydroxysteroid dehydrogenase 3 deficiency (17β-HSDD) and 5α-reductase type 2 deficiency (5α-RD) are rare 46,XY differences of sex development (DSD). This study aims to enlarge the limited knowledge on long-term gonadal function and gonadal pathology in these conditions.DesignRetrospective multicentre cohort study.MethodsData on phenotype, laboratory results, and hormone treatment were collected from patients aged ≥16 years at time of data collection with genetically confirmed 17β-HSDD and 5α-RD from 10 centres via the I-DSD Registry. If gonadectomy or gonadal biopsy had been performed, pathology reports and/or gonadal tissue or images were collected.ResultsAll 16 patients with 17β-HSDD were raised female; 1 (6%) changed to male gender at age 14. Three females were treated with gonadotrophin-releasing hormone agonists (GnRHa) to prevent virilisation. Thirteen underwent gonadectomy at median age 8 (range 0-17). None had germ cell (pre)malignancies. Of 14 patients with 5α-RD, 10 (71%) were raised female. Five changed gender at age 7-23, of whom 4 to male gender. One was treated with GnRHa. Six underwent gonadectomy at median age 10 (range 0-31). None had germ cell (pre)malignancies. With gonads in situ, puberty spontaneously progressed. Three were treated with dihydrotestosterone.ConclusionsA significant percentage of individuals with 17β-HSDD and 5α-RD changed gender, and some were treated with GnRHa to prevent virilisation before making a definitive decision about gonadectomy. When left in situ, spontaneous puberty occurs and germ cell (pre)malignancies seem uncommon at least until early adulthood. Together, these data support delaying a decision about gonadectomy until late adolescence in these conditions.

01 Jan 2025·Environmental Research

In-utero exposure to real-life environmental chemicals disrupts gene expression within the hypothalamo-pituitary-gonadal axis of prepubertal and adult rams

Article

Author: Lea, Richard G. ; Sinclair, Kevin D. ; Sinclair, Kevin D ; Bellingham, Michelle ; Evans, Neil P ; Lea, Richard G ; Ghasemzadeh Hasankolaei, Mohammad ; Elcombe, Chris S. ; Padmanabhan, Vasantha ; Evans, Neil P. ; Elcombe, Chris S

Environmental chemicals (ECs) have been associated with a broad range of disorders and diseases. Daily exposure to various ECs in the environment, or real-life exposure, has raised significant public health concerns. Utilizing the biosolids-treated pasture (BTP) sheep model, this study demonstrates that in-utero exposure to a real-life EC mixture disrupts hypothalamo-pituitary-gonadal (HPG) axis gene expression and reproductive traits in prepubertal (8-week-old, 8w) and adult (11-month-old) male sheep. Ewes were maintained on either BTP or pastures fertilized with inorganic fertilizer [control (C)] from approximately one month prior to insemination until around parturition. Thereafter, all animals were kept under control conditions. Effects on reproductive parameters including testosterone concentrations and the expression of key genes in the HPG axis were evaluated in eight-week-old and adult male offspring from both C and biosolids-exposed (B) groups. Results showed that, at 8w, relative to C (n = 11), B males (n = 11) had lower body weight, and altered testicular expression of HSD3B1, LHR and HSD17B3, BMP4, ABP, P27^kip and CELF1. Principal component analysis (PCA) identified two 8w B subgroups, based on hypothalamic expression of GnRH, ESR1, and AR, and pituitary expression of KISSR. The two subgroups also exhibited different serum testosterone concentrations. The largest biosolids effects were observed in the hypothalamus of adult rams with NKB, ESR1, KISS1, AR, DLK1 and GNRH1 mRNA expression differing between B (n = 10) and C (n = 11) rams. Testicular steroidogenic enzymes CYP11A1 and HSD3B1 mRNA expression also differed between exposure groups. PCA identified two adult B subgroups, with BS1 (n = 6) displaying hypothalamic effects and BS2 (n = 4) both hypothalamic and testicular effects. The subgroups also differed in circulating testosterone concentrations. These findings demonstrate that exposure to a real-life EC mixture may predispose some males to infertility, by disrupting key functional HPG markers before puberty with consequent downstream effects on steroid hormones and spermatogenesis.

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17β-HSD3

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