Regulation of Steroidogenesis

Bremer, Andrew A.; Miller, Walter L.

doi:10.1016/b978-0-12-408134-5.00013-5

Cited by 33 publications

(27 citation statements)

References 59 publications

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“…CYP17A1 catalyzes the conversion of pregnenolone to dehydroepiandrosterone which is converted to testosterone via downstream reactions catalyzed by 3ß-HSD and 17ß-HSD. 57 Our findings are in agreement with others who reported downregulation of testicular steroidogenic enzymes by Pb exposure. 23,49,58 The reduced levels of these hormones in conjunction with the decreased expression of steroidogenic genes confirm the toxicity of Pb on endocrine and reproductive organs.…”

Section: Discussionsupporting

confidence: 93%

<p>Umbelliferone Inhibits Spermatogenic Defects and Testicular Injury in Lead-Intoxicated Rats by Suppressing Oxidative Stress and Inflammation, and Improving Nrf2/HO-1 Signaling</p>

Alotaibi¹,

Al-Joufi²,

Seif³

et al. 2020

DDDT

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Introduction: Lead (Pb) is an environmental toxic metal that threatens human health. Umbelliferone (UMB) is a coumarin with known medicinal and protective properties against cytotoxicity. This study explored the ameliorative effect of UMB against Pb-induced testicular toxicity in rats, focusing on steroidogenesis, oxidative stress and inflammation. Materials and Methods: Rats received lead acetate (50 mg/kg) and UMB (25, 50 or 100 mg/kg) via oral gavage for 4 weeks. Results: Pb-intoxicated rats exhibited testicular tissue injury and decreased serum levels of LH, FSH and testosterone. The count, viability, motility and normal morphology of the sperms were decreased accompanied with downregulated steroidogenesis markers in Pbinduced group. UMB prevented testicular injury, increased serum levels of LH, FSH and testosterone, upregulated steroidogenesis markers and improved the semen quality. In addition, UMB attenuated oxidative stress and oxidative DNA damage, downregulated the expression of pro-inflammatory mediators and Bax, boosted antioxidant defenses and Bcl-2, and upregulated Nrf2/HO-1 signaling in Pb-intoxicated rats. Conclusion: UMB prevents Pb-induced testicular injury by suppressing oxidative damage, inflammation and cell death, and boosting antioxidant defenses, Nrf2/HO-1 signaling and pituitary-gonadal axis. Thus, UMB may represent a protective and cost-effective agent against Pb testicular toxicity, pending further investigations to elucidate other underlying mechanisms.

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Section: Discussionsupporting

confidence: 93%

<p>Umbelliferone Inhibits Spermatogenic Defects and Testicular Injury in Lead-Intoxicated Rats by Suppressing Oxidative Stress and Inflammation, and Improving Nrf2/HO-1 Signaling</p>

Alotaibi¹,

Al-Joufi²,

Seif³

et al. 2020

DDDT

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“…StAR transports cholesterol (the substrate for steroidogenesis) from the outer mitochondrial membrane into the inner mitochondrial membrane, where the first enzymatic step in steroidogenesis occurs. Worthy of note is that the rapid upsurge of steroidogenesis following copious LH release (in physiological state) is entirely dependent on the response of StAR to transport cholesterol from the outer to the inner mitochondrial membrane where CYP11A1 resides (Bremer & Miller, ). For this reason, StAR and CYP11A1 both constitute the rate‐limiting step in steroidogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Beyond the first enzymatic step in steroidogenesis, we also observed several fold reduction in the mRNA transcript and protein levels of 3β‐HSD and 17β‐HSD, while CYP17A1 mRNA transcript level decreased marginally in DC group, suggestive of a suppressive effect on steroidogenesis. CYP17A1 catalyzes the synthesis of dehydroepiandrosterone (DHEA) from pregnenolone, while 3β‐HSD and 17β‐HSD catalyze the downstream reactions leading to the synthesis of testosterone from DHEA (Bremer & Miller, ). Consistent with our findings, Ding et al .…”

Section: Discussionmentioning

confidence: 99%

Down‐regulation of steroidogenesis‐related genes and its accompanying fertility decline in streptozotocin‐induced diabetic male rats: ameliorative effect of metformin

et al. 2018

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Background: Metformin has long been used for glycemic control in diabetic state. Recently, other benefits of metformin beyond blood glucose regulation have emerged. Objectives: To investigate the effect of metformin on the expression of testicular steroidogenesis-related genes, spermatogenesis, and fertility of male diabetic rats. Materials and methods: Eighteen adult male Sprague Dawley rats were divided into three groups, namely normal control (NC), diabetic control (DC), and metformin-treated (300 mg/kg body weight/day) diabetic rats (D+Met). Diabetes was induced using a single intraperitoneal injection of streptozotocin (60 mg/kg b.w.), followed by oral treatment with metformin for four weeks. Results: Diabetes decreased serum and intratesticular testosterone levels and increased serum but not intratesticular levels of luteinizing hormone. Sperm count, motility, viability, and normal morphology were decreased, while sperm nuclear DNA fragmentation was increased in DC group, relative to NC group. Testicular mRNA levels of androgen receptor, luteinizing hormone receptor, cytochrome P450 enzyme (CYP11A1), steroidogenic acute regulatory (StAR) protein, 3b-hydroxysteroid dehydrogenase (HSD), and 17b-HSD, as well as the level of StAR protein and activities of CYP11A1, 3b-HSD, and 17b-HSD, were decreased in DC group. Similarly, decreased activities of epididymal antioxidant enzymes and increased lipid peroxidation were observed in DC group. Consequently, decreased litter size, fetal weight, mating and fertility indices, and increased pre-and post-implantation losses were recorded in DC group. Following intervention with metformin, we observed increases in serum and intratesticular testosterone levels, Leydig cell count, improved sperm parameters, and decreased sperm nuclear DNA fragmentation. Furthermore, mRNA levels and activities of steroidogenesis-related enzymes were increased, with improved fertility outcome. Discussion and conclusion: Diabetes mellitus is associated with dysregulation of steroidogenesis, abnormal spermatogenesis, and fertility decline. Controlling hyperglycemia is therefore crucial in preserving male reproductive function. Metformin not only regulates blood glucose level, but also preserves male fertility in diabetic state. Research has shown that DM impairs several aspects of the male reproductive function (Nna et al., 2017a). Decreased daily sperm production, sperm count, motility and viability, increased 110

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“…In the normal endometrium, the proliferative effects of oestrogen are normally countered by progesterone but in the absence of progesterone, oestrogen can induce oncogenesis, an effect that is amplified in situations of excess oestrogen(49). In addition to being a source of N-nitroso compounds, processed meat is also rich in cholesterol, which can be converted to androgens and oestrogens through varying metabolic pathways(50).…”

Section: Discussionmentioning

confidence: 99%

Diet and risk of breast, endometrial and ovarian cancer: UK Women’s Cohort Study

2018

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This study aimed to investigate associations between diet and the risk of breast, endometrial and ovarian cancer in the UK Women’s Cohort Study. 35,372 women aged 35-69 years were enrolled between 1995 and 1998 and completed a validated 217-item food frequency questionnaire. The individual foods were collapsed into 64 main food groups, compared using Cox proportional models, adjusting for potential confounders. Hazard ratio (HR) estimates are presented per portion increase of food items. After approximately 18 years of follow-up, there were 1822, 294, and 285 cases of breast, endometrial and ovarian cancer respectively. A high consumption of processed meat and total meat was associated with an increased risk of breast and endometrial cancer. High intakes of tomatoes (HR: 0.87, 99% confidence interval (CI): 0.75 to 1.00) and dried fruits (HR: 0.60, 99% CI: 0.37 to 0.97) were associated with a reduced risk of breast and endometrial cancer respectively. Mushroom intake was associated with a higher risk of ovarian cancer (HR 1.57, 99% CI: 1.09 to 2.26). Subgroup analysis by pre or post-menopausal cancer further demonstrated an association between processed meat intake and both postmenopausal breast cancer and endometrial cancer. Dried fruits intake was associated with a reduced risk of postmenopausal endometrial cancer (HR: 0.55, 99% CI: 0.31 to 0.98). Our findings suggest that while some foods may trigger the risk of these cancers, some foods may also be protective; supporting the call for further randomised controlled trials of dietary interventions to reduce risk of cancer among pre and postmenopausal women.

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Regulation of Steroidogenesis

Cited by 33 publications

References 59 publications

<p>Umbelliferone Inhibits Spermatogenic Defects and Testicular Injury in Lead-Intoxicated Rats by Suppressing Oxidative Stress and Inflammation, and Improving Nrf2/HO-1 Signaling</p>

<p>Umbelliferone Inhibits Spermatogenic Defects and Testicular Injury in Lead-Intoxicated Rats by Suppressing Oxidative Stress and Inflammation, and Improving Nrf2/HO-1 Signaling</p>

Down‐regulation of steroidogenesis‐related genes and its accompanying fertility decline in streptozotocin‐induced diabetic male rats: ameliorative effect of metformin

Diet and risk of breast, endometrial and ovarian cancer: UK Women’s Cohort Study

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