Steroidogenic machinery in the adult rat colon

Diviccaro, Silvia; Giatti, Silvia; Borgo, Francesca; Falvo, Eva; Caruso, Donatella; García‐Segura, Luis M.; Melcangi, Roberto Cosimo

doi:10.1016/j.jsbmb.2020.105732

Cited by 17 publications

(17 citation statements)

References 56 publications

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“…Interestingly, in the context of the growing literature regarding the role of the gut microbiota‐brain axis in human health and disease, 52‐57 it is important to highlight that, as recently demonstrated, local steroidogenesis also occurs in the adult male rat colon 58 . In particular, the levels of ALLO detected in this tissue are significantly higher than those present in plasma.…”

Section: Synthesis and Mechanism Of Actionmentioning

confidence: 98%

“…In addition, the mRNA levels of 3α-HSOR present in the adult male rat colon are significantly higher than those present in the cerebral cortex. 58 The metabolic conversions by the enzymes 5α-R, 3α-HSOR and 3β-HSOR have a deep impact on the mechanism of action of PROG. Indeed, although DHP, similar to its precursor, is still able to interact with intracellular PROG receptor, ALLO and isoallopregnanolone interact with GABA A receptor.…”

Section: Synthe S Is and Mechanis M Of Ac Ti O Nmentioning

confidence: 99%

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Allopregnanolone: An overview on its synthesis and effects

Diviccaro

Cioffi

Falvo

et al. 2021

J Neuroendocrinology

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Allopregnanolone, a 3α,5α‐progesterone metabolite, acts as a potent allosteric modulator of the γ‐aminobutyric acid type A receptor. In the present review, the synthesis of this neuroactive steroid occurring in the nervous system is discussed with respect to physiological and pathological conditions. In addition, its physiological and neuroprotective effects are also reported. Interestingly, the levels of this neuroactive steroid, as well as its effects, are sex‐dimorphic, suggesting a possible gender medicine based on this neuroactive steroid for neurological disorders. However, allopregnanolone presents low bioavailability and extensive hepatic metabolism, limiting its use as a drug. Therefore, synthetic analogues or a different therapeutic strategy able to increase allopregnanolone levels have been proposed to overcome any pharmacokinetic issues.

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Section: Synthesis and Mechanism Of Actionmentioning

confidence: 98%

Section: Synthe S Is and Mechanis M Of Ac Ti O Nmentioning

confidence: 99%

Allopregnanolone: An overview on its synthesis and effects

Diviccaro

Cioffi

Falvo

et al. 2021

J Neuroendocrinology

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“…Indeed, GABA-A receptors have been recently identified in the mouse colon [69,70]. Interestingly, we recently observed that rat colon expresses steroidogenic capability and, in particular, an high production of a T metabolite, such as the 3α-diol [71]. It is important to note that this androgen metabolite, like THP, is able to interact with GABA-A receptors [72] and its levels are affected in PFS patients as well as in its experimental model [14,21,22,28].…”

Section: Discussionmentioning

confidence: 97%

Alterations of gut microbiota composition in post-finasteride patients: a pilot study

Borgo

Macandog

Diviccaro

et al. 2020

J Endocrinol Invest

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Purpose Post-finasteride syndrome (PFS) has been reported in a subset of patients treated with finasteride (an inhibitor of the enzyme 5alpha-reductase) for androgenetic alopecia. These patients showed, despite the suspension of the treatment, a variety of persistent symptoms, like sexual dysfunction and cognitive and psychological disorders, including depression. A growing body of literature highlights the relevance of the gut microbiota-brain axis in human health and disease. For instance, alterations in gut microbiota composition have been reported in patients with major depressive disorder. Therefore, we have here analyzed the gut microbiota composition in PFS patients in comparison with a healthy cohort. Methods Fecal microbiota of 23 PFS patients was analyzed by 16S rRNA gene sequencing and compared with that reported in ten healthy male subjects. Results Sexual dysfunction, psychological and cognitive complaints, muscular problems, and physical alterations symptoms were reported in more than half of the PFS patients at the moment of sample collection. The quality sequence check revealed a low library depth for two fecal samples. Therefore, the gut microbiota analyses were conducted on 21 patients. The α-diversity was significantly lower in PFS group, showing a reduction of richness and diversity of gut microbiota structure. Moreover, when visualizing β-diversity, a clustering effect was found in the gut microbiota of a subset of PFS subjects, which was also characterized by a reduction in Faecalibacterium spp. and Ruminococcaceae UCG-005, while Alloprevotella and Odoribacter spp were increased compared to healthy control. Conclusion Gut microbiota population is altered in PFS patients, suggesting that it might represent a diagnostic marker and a possible therapeutic target for this syndrome.

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“…found that levels of T metabolites, including DHT, 3α‐diol, and 17β‐E, were significantly higher in the colon than in plasma, and levels of 3α‐diol were significantly higher than those observed in the cerebral cortex. There were no significant differences in DHT and 17β‐E concentrations in the colon compared to those in the cerebral cortex 59 . Specific bacteria for example, Butyricicoccus desmolans and Clostridium scindens ATCC 35704 , transform and utilize sex steroids by steroid‐metabolizing enzymes 60 .…”

Section: Gut Microbiome and Male Infertilitymentioning

confidence: 89%

“…There were no significant differences in DHT and 17β-E concentrations in the colon compared to those in the cerebral cortex. 59 Specific bacteria for example, Butyricicoccus desmolans and Clostridium scindens ATCC 35704, transform and utilize sex steroids by steroidmetabolizing enzymes. 60 In turn, sex steroids may also regulate the structure and function of GM.…”

Section: Gut Microbiome and Sexual Hormonesmentioning

confidence: 99%

Exploring the role of gut microbiome in male reproduction

Wang

Zuo-gang

2022

Andrology

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Background The impact of the gut microbiome on the organism has become a growing research focus with the development of 16S rRNA sequencing. However, the effect of the gut microbiome in male reproduction has yet to be investigated. Objective To overview on possible mechanisms by which the gut microbiome could affect male reproduction and therapeutic opportunities related to the gut microbiome Methods Authors searched PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane Library for medical subject headings terms and free text words referred to “male infertility” “testis” “gut microbiome” “insulin resistance” “erectile dysfunction” “therapy” “sex hormones” and “genital diseases” until December 2, 2021. Results Evidence suggests that immune system activation caused by the gut microbiome translocation not only leads to testicular and epididymal inflammation but can also induce insulin resistance together with gastrointestinal hormones such as leptin and ghrelin, which in turn affects the secretion of various sex hormones such as LH, FSH, and T to regulate spermatogenesis. In addition, the gut microbiome can influence spermatogenesis by controlling and metabolizing androgens as well as affecting the blood–testis barrier. It also promotes vascular inflammation by raising trimethylamine‐N‐oxide (TMAO) levels in the blood, which causes erectile dysfunction. The testicular microbiome and gut microbiome can interact to influence male reproductive function. This study discusses therapeutic options such as probiotics, prebiotics, and fecal microbiota transplantation, as well as the challenges and opportunities behind ongoing research, and emphasizes the need for additional research in the future to demonstrate the links and underlying mechanisms between the gut microbiome and male reproduction. Therapeutic options such as probiotics, prebiotics, and fecal microbiota transplantation are potential treatments for male infertility. Discussion and conclusion Gut microbiota may have a causal role in male reproduction health, therapeutic strategies such as supplementation with appropriate probiotics could be undertaken as a complementary treatment. In the future, additional research is needed to demonstrate the links and underlying mechanisms between the gut microbiome and male reproduction.

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Steroidogenic machinery in the adult rat colon

Cited by 17 publications

References 56 publications

Allopregnanolone: An overview on its synthesis and effects

Allopregnanolone: An overview on its synthesis and effects

Alterations of gut microbiota composition in post-finasteride patients: a pilot study

Exploring the role of gut microbiome in male reproduction

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