Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Ablation of the canonical testosterone production pathway via knockout of the steroidogenic enzyme HSD17B3, reveals a novel mechanism of testicular testosterone production

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Influence of FGF23 and Klotho on male reproduction: Systemic vs direct effects

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Prenatal inflammation suppresses blood Th1 polarization and gene clusters related to cellular energy metabolism in preterm newborns

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Muscle-strain injury exudate favors acute tissue healing and prolonged connective tissue formation in humans

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Presence of parabens, phenols and phthalates in paired maternal serum, urine and amniotic fluid

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Treatment options for hypercalcemia after cosmetic oil injections: Lessons from human tissue cultures and a pilot intervention study

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Endocrine Disrupting Chemicals and Risk of Testicular Cancer: A Systematic Review and Meta-analysis

    Research output: Contribution to journalReviewResearchpeer-review

  4. Accelerated loss of oogonia and impaired folliculogenesis in females with Turner syndrome start during early fetal development

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Associations of serum phthalate metabolites with thyroid hormones in GraMo cohort, Southern Spain

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Male development, fertility, and lifelong health are all androgen-dependent. Approximately 95% of circulating testosterone is synthesized by the testis and the final step in this canonical pathway is controlled by the activity of the hydroxysteroid-dehydrogenase-17-beta-3 (HSD17B3). To determine the role of HSD17B3 in testosterone production and androgenization during male development and function we have characterized a mouse model lacking HSD17B3. The data reveal that developmental masculinization and fertility are normal in mutant males. Ablation of HSD17B3 inhibits hyperstimulation of testosterone production by hCG, although basal testosterone levels are maintained despite the absence of HSD17B3. Reintroduction of HSD17B3 via gene-delivery to Sertoli cells in adulthood partially rescues the adult phenotype, showing that, as in development, different cell-types in the testis are able to work together to produce testosterone. Together, these data show that HS17B3 acts as a rate-limiting-step for the maximum level of testosterone production by the testis but does not control basal testosterone production. Measurement of other enzymes able to convert androstenedione to testosterone identifies HSD17B12 as a candidate enzyme capable of driving basal testosterone production in the testis. Together, these findings expand our understanding of testosterone production in males.

Original languageEnglish
JournalFASEB Journal
Volume34
Issue number8
Pages (from-to)10373-10386
Number of pages14
ISSN0892-6638
DOIs
Publication statusPublished - Aug 2020

    Research areas

  • androgens, HSD17B12, HSD17B3, Leydig cell, testis, testosterone

ID: 60197400