Cytochrome P-45017α in β-cells of rat pancreas and its local steroidogenesis

Ogishima, Tadashi; Mitani, Fumiko; Suematsu, Makoto

doi:10.1016/j.jsbmb.2008.04.008

Cited by 19 publications

(12 citation statements)

References 40 publications

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“…Co-localization of P-450scc and 3β-hydroxysteroid dehydrogenase (3βHSD), which converts pregnenolone to P4 and DHEA to androstenedione (Fig. 1) was also found in rat β-cells [16]. This indicates that P4 is intracellularly produced in rat β-cells and converted to androstenedione.…”

Section: Evidence Of Local Islet Steroidogenesismentioning

confidence: 89%

“…P-450scc, and P-450 17α , which has 17α-hydroxylase activity and C17–C20 lyase activity, the latter a prerequisite for androgen biosynthesis, were found to be co-localized in rat islet β-cells (Fig.1). This suggests that P4 is intracellularly produced and is converted to androstenedione [16]. Co-localization of P-450scc and 3β-hydroxysteroid dehydrogenase (3βHSD), which converts pregnenolone to P4 and DHEA to androstenedione (Fig.…”

Section: Evidence Of Local Islet Steroidogenesismentioning

confidence: 99%

See 1 more Smart Citation

Role of Sex Steroids in β Cell Function, Growth, and Survival

Mauvais-Jarvis

2016

Trends in Endocrinology & Metabolism

104

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The gonads have long been considered as endocrine glands producing sex steroids such as estrogens, androgens and progesterone, for the sole purpose of sexual differentiation, puberty and reproduction. Reproduction and energy metabolism are tightly linked, however, and gonadal steroids play an important role in sex-specific aspects of energy metabolism in different physiological conditions. In that respect, gonadal steroids also influence the secretion of insulin in a sex-specific manner. This review presents a perspective on the physiological roles of estrogen, androgen and progesterone via their receptors in pancreatic β-cells in the gender-specific tuning of insulin secretion. We also discuss potential gender-specific therapeutic avenues that this knowledge may open in the future.

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Section: Evidence Of Local Islet Steroidogenesismentioning

confidence: 89%

Section: Evidence Of Local Islet Steroidogenesismentioning

confidence: 99%

Role of Sex Steroids in β Cell Function, Growth, and Survival

Mauvais-Jarvis

2016

Trends in Endocrinology & Metabolism

104

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“…One of these studies [93] found the presence of Cyt P-45017␣ and P-450ssc, enzymes that participate in androgen de novo synthesis from cholesterol. Studies by our group found the presence of steroidogenic factor 1(SF-1) and 2 (SF-2) [94], and steroidogenic acute regulatory protein (StAR), and P-450ssc [95], key proteins participating in the steroid synthesis pathway.…”

Section: Effects Of Androgens On the Endocrine Pancreasmentioning

confidence: 99%

Sex steroids effects on the endocrine pancreas

Morimoto

Escobedo-Morales

Zambrano

et al. 2010

The Journal of Steroid Biochemistry and Molecular Biology

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“…It is not clear by what mechanism androstenedione administration would induce these neoplasms, but the mouse pancreatic islet β cells express the androgen receptor, which may play a role in β-cell proliferation (Li et al, 2008). CYP 17, the steroidogenic enzyme responsible for converting progestins to androgens, has been identified in rat pancreatic islets (Ogishima et al, 2008), but has yet to be identified in mouse islet cells. The relation of androgens, pancreatic islet cells, and insulin is not well understood, but it is of interest due to polycystic ovary syndrome, in which individuals have increased levels of circulating androstenedione, and decreased insulin sensitivity (Schuring et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Toxicity and carcinogenicity of androstenedione in F344/N rats and B6C3F1 mice

Blystone

Elmore

Witt

et al. 2011

Food and Chemical Toxicology

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Androstenedione was marketed as a dietary supplement to increase muscle mass during training. Due to concern over long-term use, the NTP evaluated the subchronic and chronic toxicity and carcinogenicity of androstenedione in male and female F344/N rats and B6C3F1 mice. In subchronic studies, dose limiting effects were not observed. A chronic (two-year) exposure by gavage at 10, 20, or 50 mg/kg in rats and male mice, and 2, 10, or 50 mg/kg in female mice (50 mg/kg, maximum feasible dose) was conducted. Increased incidences of lung alveolar/bronchiolar adenoma and carcinoma occurred in the 20 mg/kg male rats and increases in mononuclear cell leukemia occurred in the 20 and 50 mg/kg female rats, which may have been related to androstenedione administration. In male and female mice, androstenedione was carcinogenic based upon a significant increase in hepatocellular tumors. A marginal increase in pancreatic islet cell adenomas in male (50 mg/kg) and female (2, 10, 50 mg/kg) mice was considered to be related to androstenedione administration. Interestingly, incidences of male rat Leydig cell adenomas and female rat mammary gland fibroadenomas decreased. In conclusion, androstenedione was determined to be carcinogenic in male and female mice, and may have been carcinogenic in rats.

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Cytochrome P-45017α in β-cells of rat pancreas and its local steroidogenesis

Cited by 19 publications

References 40 publications

Role of Sex Steroids in β Cell Function, Growth, and Survival

Role of Sex Steroids in β Cell Function, Growth, and Survival

Sex steroids effects on the endocrine pancreas

Toxicity and carcinogenicity of androstenedione in F344/N rats and B6C3F1 mice

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