Effect of insulin and testosterone on androgen production and transcription of SULT2A1 in the NCI-h295r adrenocortical cell line

Kumar, Abhishek; Magoffin, Denis A.; Iqbal, Munir; Azziz, Ricardo

doi:10.1016/j.fertnstert.2008.05.076

Cited by 13 publications

(10 citation statements)

References 34 publications

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“…3B-E). Since Cyp17 gene expression is induced by both androgen and insulin (32, 33), it is unsurprising that Cyp17 levels were normalized in L/P mice that had reduced circulating levels of testosterone and insulin. On the other hand, it is not clear why Fshr mRNA levels were increased in both L/L and L/P mice.…”

Section: Resultsmentioning

confidence: 99%

Exposure to a Healthy Gut Microbiome Protects Against Reproductive and Metabolic Dysregulation in a PCOS Mouse Model

Torres

Ho²,

Arroyo³

et al. 2018

Preprint

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48Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting approximately 49 10% of reproductive-aged women worldwide. Diagnosis requires two of the following: 50 hyperandrogenism, oligo/anovulation and polycystic ovaries. In addition to reproductive 51 dysfunction, many women with PCOS display metabolic abnormalities associated with 52hyperandrogenism. Recent studies have reported that the gut microbiome is altered in women 53with PCOS and rodent models of the disorder. However, it is unknown whether the gut 54 microbiome plays a causal role in the development and pathology of PCOS. Given its potential 55role, we hypothesized that exposure to a healthy gut microbiome would protect against 56 development of PCOS. A co-housing study was performed using a letrozole-induced PCOS 57 mouse model that recapitulates many reproductive and metabolic characteristics of PCOS. Since 58 mice are coprophagic, co-housing results in repeated, non-invasive inoculation of gut microbes 59 in co-housed mice via the fecal-oral route. In contrast to letrozole-treated mice housed together, 60letrozole-treated mice co-housed with placebo mice showed significant improvement in both 61reproductive and metabolic PCOS phenotypes. Using 16S rRNA gene sequencing, we observed 62 that the gut microbial composition of letrozole-treated mice co-housed with placebo mice 63 differed from letrozole mice housed together. In addition, our analyses identified several 64 bacterial taxa including Coprobacillus, Dorea and Adlercreutzia associated with the improved 65PCOS phenotype in letrozole-treated mice co-housed with placebo mice. These results indicate 66 that disruption of the gut microbiome may play a causal role in PCOS and that manipulation of 67 the gut microbiome may be a potential treatment option for PCOS. 68 69Significance: 70 71PCOS is a common cause of female infertility and ~80% of women with PCOS have metabolic 72 dysregulation that predisposes them to type 2 diabetes and cardiovascular disease. Since 73 treatment options for the metabolic symptoms of PCOS are limited, there is a need to develop 74 novel therapeutic options. The gut microbiome has emerged as an important player in human 75health and has been shown to play a causal role in obesity. In this study, we found that exposure 76to a healthy gut microbiome through co-housing protected against the development of 77reproductive and metabolic dysregulation in a PCOS mouse model. These results suggest that 78 manipulation of the gut microbiome may be a potential treatment option for women with PCOS. 79 80Introduction: 81 82Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting approximately 83 10% of women worldwide (1). Diagnosis of PCOS, using the Rotterdam Consensus criteria 84 (2003), requires two of the following: hyperandrogenism, oligo-or amenorrhea and polycystic 85ovaries. PCOS is the leading cause of anovulatory infertility in women, and women with PCOS 86also have an increased likelihood of miscarriage and pregnancy complications. Though ...

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Section: Resultsmentioning

confidence: 99%

Exposure to a Healthy Gut Microbiome Protects Against Reproductive and Metabolic Dysregulation in a PCOS Mouse Model

Torres

Ho²,

Arroyo³

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…In cadaveric adrenocortical minces, T has no predictable effect on the ACTH-stimulated production of DHEA or F (4). In addition, while T increases the production of DHEA in adrenocortical cell lines, it decreases DHEAS secretion (5). Our current finding that DHEAS and DHEA levels, and ACTH-stimulated DHEA secretion, are unchanged following oophorectomy are consistent with these results, and suggest that ovarian factors play a limited role in the adrenocortical dysfunction and adrenal androgen excess of PCOS.…”

Section: Discussionmentioning

confidence: 99%

“…However, we found that T had no predictable effect on the production of DHEA, DHEAS or F in human adrenal tissue in vitro (4). Alternatively, studies in NCI-H295R adrenocortical cell lines indicated that while T increased the production of DHEA, it appeared to decrease the secretion of DHEAS (5). Overall, T appears to have only a modest effect on AA secretion, primarily increasing the sulfation of DHEA to DHEAS, and does not result in an exaggerated secretion of active androgens.…”

Section: Introductionmentioning

confidence: 99%

Effect of bilateral oophorectomy on adrenocortical function in women with polycystic ovary syndrome

Azziz

Chang

Stanczyk

et al. 2013

Fertility and Sterility

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Objective To determine the impact of ovary-secreted products on adrenocortical function in women with PCOS by studying the adrenocortical response to acute adrenocorticotropic-stimulating hormone (ACTH) stimulation before and after bilateral oophorectomy. Design Prospective study. Setting Tertiary care medical center Participants Fourteen women with PCOS scheduled for bilateral oophorectomy for benign indications, on transdermal estradiol (E2) postoperatively. Interventions Physical exam, blood sampling before and after oophorectomy, measurement of hormone levels. Basal (Steroid0), maximum stimulated (Steroid60), and net increment (ΔSteroid) levels of androstenedione (A4), dehydroepiandrosterone (DHEA), and cortisol (F) before and after ACTH-1–24 stimulation were assessed. Main Outcome Measures Pre- and post-operative basal and ACTH(1–24)-stimulated hormonal levels. Results Total testosterone, free testosterone, and estrone levels decreased, and FSH levels increased significantly following oophorectomy. No significant differences in E2, DHEA sulfate (DHEAS) or sex hormone binding globulin levels were detected. Basal and ACTH-stimulated A4 levels decreased significantly following oophorectomy, and ΔA4 was significantly increased. No significant differences in DHEA0, DHEA60, or F0 levels were detected; F60 and ΔF levels tended to increase following oophorectomy, but the differencesdid not reach significance. Conclusions Ovarian factors do not appear to contribute significantly to the adrenocortical dysfunction of PCOS.

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“…However, in minced human adrenal tissue insulin failed to show a consistent effect on androgen production(21). Further studies using a human adrenocortical cell line, co-incubation with insulin was not associated with increases of T and DHEAS(22). In contrast, there is clinical evidence in humans to suggest that hyperinsulinemia or hyperglycemia may decrease adrenal androgen levels(23, 24).…”

Section: Discussionmentioning

confidence: 99%

Androgen responses to adrenocorticotropic hormone infusion among individual women with polycystic ovary syndrome

Maas

Chuan

Harrison

et al. 2016

Fertility and Sterility

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Objective To compare androgen responses during ACTH infusion among women with PCOS and normal women. Design Cross-sectional study. Setting Research center at an academic medical center. Participants Women with PCOS (n=13) and normal controls (n=15). Interventions Blood samples were obtained frequently during a 6-hour dose-response ACTH infusion. Main Outcome Measures Comparison of basal and stimulated levels of 17-OHP, androgens, and cortisol during ACTH infusion with those following hCG injection within individual subjects. Results In women with PCOS increased 17-OHP, A4, and DHEA responses during ACTH infusion were comparable to those observed in normal controls. The magnitude of responses was highly variable among PCOS women. Within individual women with PCOS adrenal responses to ACTH and ovarian responses to hCG were significantly correlated. Cortisol responses to ACTH were similar in PCOS and normal controls. Conclusion Within individual women with PCOS, enhanced androgen responses to ACTH are accompanied by comparable androgen responsiveness to hCG. These findings suggest that dysregulated steroidogenesis leading to hyperandrogenemia in this disorder is likely present in both adrenal and ovarian tissues.

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Effect of insulin and testosterone on androgen production and transcription of SULT2A1 in the NCI-h295r adrenocortical cell line

Cited by 13 publications

References 34 publications

Exposure to a Healthy Gut Microbiome Protects Against Reproductive and Metabolic Dysregulation in a PCOS Mouse Model

Exposure to a Healthy Gut Microbiome Protects Against Reproductive and Metabolic Dysregulation in a PCOS Mouse Model

Effect of bilateral oophorectomy on adrenocortical function in women with polycystic ovary syndrome

Androgen responses to adrenocorticotropic hormone infusion among individual women with polycystic ovary syndrome

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