PXD050748

PXD050748 is an original dataset announced via ProteomeXchange.

Title	Identifying a novel hydroxysteroid dehydrogenase enzyme that is capable of testosterone biosynthesis in the mouse
Description	Androgens, such as testosterone and dihydrotestosterone (DHT), are essential for male sexual development, masculinisation, spermatogenesis, and general lifelong health. Androgens are predominantly synthesised in the testes of mice (~95%) by highly specialised cells known as the Leydig cells. There are two known androgen production pathways in the testes of mice: (i) the canonical pathway which synthesises testosterone which can be used as a substrate for the more potent DHT, and (ii) the alternate pathway which can synthesise DHT without the need for testosterone. The HSD17B3 enzyme is a key enzyme in the canonical pathway which converts androstenedione into testosterone and the SRD5A1 enzyme is the predominant 5α-reductase in the testes that converts androgen precursors into the alternate pathway. HSD17B3 deficiency in humans results in a disorder of sexual development with 46,XY individuals appearing with female or ambiguous external genitalia whilst having Wolffian internal structures. However, in contrast to humans, Hsd17b3 knockout (KO) mice can be identified as male from birth and throughout adulthood, remain fertile and have normal intratesticular testosterone levels indicating that compensatory mechanisms are apparent in the mouse. What these compensatory mechanisms are, be other enzymes, or other androgen production pathways, remains unknown. We have generated a mouse model incorporating wild-type (WT), Hsd17b3 KO and Hsd17b3; Srd5a1 double (d)KO mice. Proteomic analysis has been performed on WT, Hsd17b3 KO and dKO whole testis tissue to identify potential androgen compensatory mechanisms in the mouse and pathways that are impacted by the removal of the HSD17B3 or both the HSD17B3 and SRD5A1 proteins. The total proteins detected across the three groups were 2,892, 3,041, and 2813 in WT, Hsd17b3 KO and dKO testes, respectively.
HostingRepository	PRIDE
AnnounceDate	2025-05-12
AnnouncementXML	Submission_2025-05-12_06:02:10.313.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD050748
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	David Skerrett-Byrne
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-18 17:49:22	ID requested
⏵ 1	2025-05-12 06:02:11	announced

10.1210/endocr/bqaf078;

10.6019/PXD050748;

Lawrence BM, O'Donnell L, Gannon AL, Skerrett-Byrne DA, Parameswaran S, Abbott I, Smith S, Handelsman DJ, Rebourcet D, Smith LB, Functional Analysis of HSD17B3-Deficient Male Mice Reveals Roles for HSD17B7 and HSD17B12 in Testosterone Biosynthesis. Endocrinology, 166(6):(2025) [pubmed]

submitter keyword: Androgens, Alternate Pathway, HSD17B7, Canonical Pathway, testosterone, SRD5A1, Testosterone Biosynthesis, HSD17B3

Professor Lee Smith
contact affiliation	Office for Research, Griffith University, Southport, QLD 4222, Australia
contact email	Lee.smith@griffith.edu.au
lab head
David Skerrett-Byrne
contact affiliation	Helmholtz Zentrum München
contact email	David.Skerrett-Byrne@newcastle.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050748
     1. Label: PRIDE project
     2. Name: Identifying a novel hydroxysteroid dehydrogenase enzyme that is capable of testosterone biosynthesis in the mouse