New Insights into Testosterone Biosynthesis: Novel Observations from HSD17B3 Deficient Mice
Androgens such as testosterone and dihydrotestosterone (DHT) are essential for male sexual development, masculinisation, and fertility. Testosterone is produced via the canonical androgen production pathway and is essential for normal masculinisation and testis function. Disruption to androgen produ...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/24/15555 |
| _version_ | 1797457342003937280 |
|---|---|
| author | Ben M. Lawrence Liza O’Donnell Lee B. Smith Diane Rebourcet |
| author_facet | Ben M. Lawrence Liza O’Donnell Lee B. Smith Diane Rebourcet |
| author_sort | Ben M. Lawrence |
| collection | DOAJ |
| description | Androgens such as testosterone and dihydrotestosterone (DHT) are essential for male sexual development, masculinisation, and fertility. Testosterone is produced via the canonical androgen production pathway and is essential for normal masculinisation and testis function. Disruption to androgen production can result in disorders of sexual development (DSD). In the canonical pathway, 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) is viewed as a critical enzyme in the production of testosterone, performing the final conversion required. HSD17B3 deficiency in humans is associated with DSD due to low testosterone concentration during development. Individuals with <i>HSD17B3</i> mutations have poorly masculinised external genitalia that can appear as ambiguous or female, whilst having internal Wolffian structures and testes. Recent studies in mice deficient in HSD17B3 have made the surprising finding that testosterone production is maintained, male mice are masculinised and remain fertile, suggesting differences between mice and human testosterone production exist. We discuss the phenotypic differences observed and the possible other pathways and enzymes that could be contributing to testosterone production and male development. The identification of alternative testosterone synthesising enzymes could inform the development of novel therapies to endogenously regulate testosterone production in individuals with testosterone deficiency. |
| first_indexed | 2024-03-09T16:20:52Z |
| format | Article |
| id | doaj.art-965fad76db424d4e9f7c293cb2a2370b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:20:52Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-965fad76db424d4e9f7c293cb2a2370b2023-11-24T15:23:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241555510.3390/ijms232415555New Insights into Testosterone Biosynthesis: Novel Observations from HSD17B3 Deficient MiceBen M. Lawrence0Liza O’Donnell1Lee B. Smith2Diane Rebourcet3College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW 2308, AustraliaCollege of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW 2308, AustraliaCollege of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW 2308, AustraliaCollege of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW 2308, AustraliaAndrogens such as testosterone and dihydrotestosterone (DHT) are essential for male sexual development, masculinisation, and fertility. Testosterone is produced via the canonical androgen production pathway and is essential for normal masculinisation and testis function. Disruption to androgen production can result in disorders of sexual development (DSD). In the canonical pathway, 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) is viewed as a critical enzyme in the production of testosterone, performing the final conversion required. HSD17B3 deficiency in humans is associated with DSD due to low testosterone concentration during development. Individuals with <i>HSD17B3</i> mutations have poorly masculinised external genitalia that can appear as ambiguous or female, whilst having internal Wolffian structures and testes. Recent studies in mice deficient in HSD17B3 have made the surprising finding that testosterone production is maintained, male mice are masculinised and remain fertile, suggesting differences between mice and human testosterone production exist. We discuss the phenotypic differences observed and the possible other pathways and enzymes that could be contributing to testosterone production and male development. The identification of alternative testosterone synthesising enzymes could inform the development of novel therapies to endogenously regulate testosterone production in individuals with testosterone deficiency.https://www.mdpi.com/1422-0067/23/24/15555androgenstestosteroneHSD17B3enzymescanonical pathway |
| spellingShingle | Ben M. Lawrence Liza O’Donnell Lee B. Smith Diane Rebourcet New Insights into Testosterone Biosynthesis: Novel Observations from HSD17B3 Deficient Mice International Journal of Molecular Sciences androgens testosterone HSD17B3 enzymes canonical pathway |
| title | New Insights into Testosterone Biosynthesis: Novel Observations from HSD17B3 Deficient Mice |
| title_full | New Insights into Testosterone Biosynthesis: Novel Observations from HSD17B3 Deficient Mice |
| title_fullStr | New Insights into Testosterone Biosynthesis: Novel Observations from HSD17B3 Deficient Mice |
| title_full_unstemmed | New Insights into Testosterone Biosynthesis: Novel Observations from HSD17B3 Deficient Mice |
| title_short | New Insights into Testosterone Biosynthesis: Novel Observations from HSD17B3 Deficient Mice |
| title_sort | new insights into testosterone biosynthesis novel observations from hsd17b3 deficient mice |
| topic | androgens testosterone HSD17B3 enzymes canonical pathway |
| url | https://www.mdpi.com/1422-0067/23/24/15555 |
| work_keys_str_mv | AT benmlawrence newinsightsintotestosteronebiosynthesisnovelobservationsfromhsd17b3deficientmice AT lizaodonnell newinsightsintotestosteronebiosynthesisnovelobservationsfromhsd17b3deficientmice AT leebsmith newinsightsintotestosteronebiosynthesisnovelobservationsfromhsd17b3deficientmice AT dianerebourcet newinsightsintotestosteronebiosynthesisnovelobservationsfromhsd17b3deficientmice |