Diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in mice
Functional gastrointestinal disorders (FGIDs) have prominent sex differences in incidence, symptoms, and treatment response that are not well understood. Androgens are steroid hormones present at much higher levels in males than females and could be involved in these differences. In adults with irri...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2022-01-01
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| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI150789 |
| _version_ | 1811334900889944064 |
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| author | Daniella Rastelli Ariel Robinson Valentina N. Lagomarsino Lynley T. Matthews Rafla Hassan Kristina Perez William Dan Peter D. Yim Madison Mixer Aleksandra Prochera Amy Shepherd Liang Sun Kathryn Hall Sarah Ballou Anthony Lembo Judy Nee Meenakshi Rao |
| author_facet | Daniella Rastelli Ariel Robinson Valentina N. Lagomarsino Lynley T. Matthews Rafla Hassan Kristina Perez William Dan Peter D. Yim Madison Mixer Aleksandra Prochera Amy Shepherd Liang Sun Kathryn Hall Sarah Ballou Anthony Lembo Judy Nee Meenakshi Rao |
| author_sort | Daniella Rastelli |
| collection | DOAJ |
| description | Functional gastrointestinal disorders (FGIDs) have prominent sex differences in incidence, symptoms, and treatment response that are not well understood. Androgens are steroid hormones present at much higher levels in males than females and could be involved in these differences. In adults with irritable bowel syndrome (IBS), a FGID that affects 5% to 10% of the population worldwide, we found that free testosterone levels were lower than those in healthy controls and inversely correlated with symptom severity. To determine how this diminished androgen signaling could contribute to bowel dysfunction, we depleted gonadal androgens in adult mice and found that this caused a profound deficit in gastrointestinal transit. Restoring a single androgen hormone was sufficient to rescue this deficit, suggesting that circulating androgens are essential for normal bowel motility in vivo. To determine the site of action, we probed androgen receptor expression in the intestine and discovered, unexpectedly, that a large subset of enteric neurons became androgen-responsive upon puberty. Androgen signaling to these neurons was required for normal colonic motility in adult mice. Taken together, these observations establish a role for gonadal androgens in the neural regulation of bowel function and link altered androgen levels with a common digestive disorder. |
| first_indexed | 2024-04-13T17:16:03Z |
| format | Article |
| id | doaj.art-d09b2fd9c6d544b3901ac8fede389727 |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-04-13T17:16:03Z |
| publishDate | 2022-01-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-d09b2fd9c6d544b3901ac8fede3897272022-12-22T02:38:08ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382022-01-011322Diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in miceDaniella RastelliAriel RobinsonValentina N. LagomarsinoLynley T. MatthewsRafla HassanKristina PerezWilliam DanPeter D. YimMadison MixerAleksandra ProcheraAmy ShepherdLiang SunKathryn HallSarah BallouAnthony LemboJudy NeeMeenakshi RaoFunctional gastrointestinal disorders (FGIDs) have prominent sex differences in incidence, symptoms, and treatment response that are not well understood. Androgens are steroid hormones present at much higher levels in males than females and could be involved in these differences. In adults with irritable bowel syndrome (IBS), a FGID that affects 5% to 10% of the population worldwide, we found that free testosterone levels were lower than those in healthy controls and inversely correlated with symptom severity. To determine how this diminished androgen signaling could contribute to bowel dysfunction, we depleted gonadal androgens in adult mice and found that this caused a profound deficit in gastrointestinal transit. Restoring a single androgen hormone was sufficient to rescue this deficit, suggesting that circulating androgens are essential for normal bowel motility in vivo. To determine the site of action, we probed androgen receptor expression in the intestine and discovered, unexpectedly, that a large subset of enteric neurons became androgen-responsive upon puberty. Androgen signaling to these neurons was required for normal colonic motility in adult mice. Taken together, these observations establish a role for gonadal androgens in the neural regulation of bowel function and link altered androgen levels with a common digestive disorder.https://doi.org/10.1172/JCI150789GastroenterologyNeuroscience |
| spellingShingle | Daniella Rastelli Ariel Robinson Valentina N. Lagomarsino Lynley T. Matthews Rafla Hassan Kristina Perez William Dan Peter D. Yim Madison Mixer Aleksandra Prochera Amy Shepherd Liang Sun Kathryn Hall Sarah Ballou Anthony Lembo Judy Nee Meenakshi Rao Diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in mice The Journal of Clinical Investigation Gastroenterology Neuroscience |
| title | Diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in mice |
| title_full | Diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in mice |
| title_fullStr | Diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in mice |
| title_full_unstemmed | Diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in mice |
| title_short | Diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in mice |
| title_sort | diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in mice |
| topic | Gastroenterology Neuroscience |
| url | https://doi.org/10.1172/JCI150789 |
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