Immunolocalization of aromatase, 17 -hydroxylase and side-chain-cleavage cytochromes P-450 in the human ovary

Sasano, Hironobu; Okamoto, Mitsuhiro; Mason, J. Ian; Simpson, Evan R.; Mendelson, Carole R.; Sasano, Nobuaki; Silverberg, Steven G.

doi:10.1530/jrf.0.0850163

Cited by 186 publications

(80 citation statements)

References 16 publications

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“…The 17,20-lyase specific activity of P450c17 is weak in zona fasciculata, but strong in zona reticularis in order to produce DHEA and androstenedione [26]. In the ovary, the general consensus is that only thecal cells express both the 17α-hydroxylase and 17,20-lyase activities of the P450c17 enzyme [27], although one report showed the presence of P450c17 within human cultured granulosa cells [28]. Thus, androgen formation is dependent upon the 17,20-lyase/17α-hydroxylase activities ratio.…”

Section: Steroidogenesismentioning

confidence: 99%

Insulin and hyperandrogenism in women with polycystic ovary syndrome

Baptiste

Battista

Trottier

et al. 2010

The Journal of Steroid Biochemistry and Molecular Biology

259

199

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Polycystic ovary syndrome (PCOS) is a very common endocrine disorder characterized by chronic anovulation, clinical and/or biochemical hyperandrogenism, and/or polycystic ovaries. But most experts consider that hyperandrogenism is the main characteristic of PCOS. Several theories propose different mechanisms to explain PCOS manifestations: (1) a primary enzymatic default in the ovarian and/or adrenal steroidogenesis; (2) an impairment in gonadotropin releasing hormone (GnRH) secretion that promotes luteal hormone (LH) secretion; or (3) alterations in insulin actions that lead to insulin resistance with compensatory hyperinsulinemia. However, in the past 20 years there has been growing evidence supporting that defects in insulin actions or in the insulin signalling pathways are central in the pathogenesis of the syndrome. Indeed, most women with PCOS are metabolically insulin resistant, in part due to genetic predisposition and in part secondary to obesity. But some women with typical PCOS do not display insulin resistance, which supports the hypothesis of a genetic predisposition specific to PCOS that would be revealed by the development of insulin resistance and compensatory hyperinsulinemia in most, but not all, women with PCOS. However, these hypotheses are not yet appropriately confirmed, and more research is still needed to unravel the true pathogenesis underlying this syndrome. The present review thus aims at discussing new concepts and findings regarding insulin actions in PCOS women and how it is related to hyperandrogenemia.

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Section: Steroidogenesismentioning

confidence: 99%

Insulin and hyperandrogenism in women with polycystic ovary syndrome

Baptiste

Battista

Trottier

et al. 2010

The Journal of Steroid Biochemistry and Molecular Biology

259

199

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“…In granulosa cells, an increase either in the enzymes cholesterol side-chain-cleavage, cytochrome P-450 (P-450scc), 3 ß-hydroxysteroid dehydrogenase and aromatase cytochrome P-450, or in the secretion of progesterone by follicular cells is observed following the LH surge in the newly formed corpus luteum (Sano et al, 1981;Sasano et al, 1989;Doody et al, 1990). In cumulus cells, the increase in P-450scc activity occurs only in cumulus-oocyte complexes in which the oocyte has undergone germinal vesicle breakdown (Goldschmit et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

“…The cumulus cells had cell to cell contact via abundant cytoplasmic processes, which could be longer than 100 µ . With the (Bar-Ami and Gitay-Goren, 1993 (Rodgers et al, 1986;Sasano et al, 1989) and a reduction in the activities of 17a-hydroxylase:C-17-C-20 lyase (Sano et al, 1981;Suzuki and Tamaoki, 1983;Johnson, 1988 (Carson et al, 1982), in peripheral serum following hCG administration (Yovich et al, 1985) and in the spent media of human granulosa-lutein cell cultures (Hill et al, 1987; Gitay-Goren et Bar-Ami and Gitay-Goren, 1993).…”

Section: Introductionmentioning

confidence: 99%

Effect of cell-plating density on the steroidogenic activity of human cumulus cells

Bar‐Ami

Khoury²

1994

Reproduction

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Expansion of the cumulus mass results in dilution of cumulus cells in accumulated hyaluronic acid. This process is associated with an increase in progesterone secretion. The present study was carried out to evaluate the relationship between these two processes in vitro. Dilution of human cumulus cells was attempted by changing the cell-plating density of cumulus cells in culture. Concurrent with an increase in cell-plating density from 0.25 \m=x\10 to 8 \ m=x\104, progesterone secretion increased by 10.5 times (P < 0.001), 9 times (P < 0.001), and 5.9 times (P < 0.001), and oestradiol secretion increased by 1.4 times (P < 0.001), 1.1 times (P > 0.05), and 2.6 times (P < 0.005) during days 0\p=n-\3,3\p=n-\5, and 5\p=n-\7 of culture, respectively. However, when steroid secretion was expressed in terms of ng per number of cells, the increase in cell-plating density from 0.25 \m=x\104 to 8 \m=x\104 coincided with a decrease in progesterone secretion of 3 times (P < 0.001), 3.5 times (P < 0.001), and 5.4 times (P < 0.005), and oestradiol secretion decreased by 23 times (P < 0.001), 30 times (P < 0.001), and 12.5 times (P < 0.001) during days 0\p=n-\3,3\p=n-\5,and 5\p=n-\7of culture, respectively. The progesterone:oestradiol ratio increased gradually with the increase in cell-plating density. However, at the higher range of cell-plating density the progesterone: oestradiol ratio decreased with extension of the culture period. Addition of human FSH (hFSH) or hCG increased progesterone secretion when the cumulus cells were plated at 2 \m=x\104, but in most cases not at 0.25 \m=x\104 or 8 \m=x\104 cells per dish. However, both hFSH and hCG decreased oestradiol secretion at 2 \m=x\104 cells per dish. In the presence of gonadotrophins, an increase in cell contact and cytoplasmic processes during days 0\p=n-\3and 3\p=n-\5was noted. This study indicates that secretion of progesterone and oestradiol per number of cells is significantly increased with a decrease in cell-plating density. Furthermore, addition of gonadotrophin increased progesterone and decreased oestradiol secretion at the middle range of cell-plating density.

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“…29). In women, CYP17 is expressed in the ovarian theca cells, the corpus luteum, adrenals, and adipose tissue (30)(31)(32). A single nucleotide polymorphism in the 5 ¶-untranslated region of CYP17 is relatively common and the presence of the A2 allele is thought to increase transcription rates (26), although other studies suggest that no additional transcription factor binding activity is associated with the presence of the A2 allele (33,34).…”

Section: Introductionmentioning

confidence: 99%

CYP17Genotypes Differ in Salivary 17-β Estradiol Levels: A Study Based on Hormonal Profiles from Entire Menstrual Cycles

Jasieńska¹,

Kapiszewska

Ellison

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Variation in the levels of sex-steroid hormones results from differences in developmental conditions, adult lifestyle, and genetic polymorphism. Genes involved in sex-steroid biosynthesis have been implicated to influence levels of hormones in premenopausal women, but the results were inconclusive. We tested variation among women in levels of salivary estradiol (E 2 ) corresponding to CYP17 genotypes. CYP17 encodes cytochrome P450c17A, which mediates two enzymes important in E 2 synthesis. In contrast to the earlier studies that relied on one or a few samples for assessing the E 2 levels of an individual woman, our study is based on daily collected saliva samples for one entire menstrual cycle. Sixty Polish women, ages 24 to 36 years, with regular menstrual cycles and no reported fertility problems participated in the study. Women with A2/A2 genotype had 54% higher mean E 2 levels than women with A1/A1 genotype (P = 0.0001) and 37% higher than women with A1/A2 genotype (P = 0.0008). Heterozygous A1/A2 women had 13 % higher E 2 levels than homozygous A1/A1 women (but this difference was significant only in a nonparametric test). Levels of E 2 during the day with highest E 2 (day À1) were 72% higher in A2/A2 compared with A1/A1 (P = 0.01) and 52 % higher compared with A1/A2 (P = 0.03). Our results suggest that CYP17 genotype may serve as a biomarker of endocrine function in women of reproductive age. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2131 -5)

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Immunolocalization of aromatase, 17 -hydroxylase and side-chain-cleavage cytochromes P-450 in the human ovary

Cited by 186 publications

References 16 publications

Insulin and hyperandrogenism in women with polycystic ovary syndrome

Insulin and hyperandrogenism in women with polycystic ovary syndrome

Effect of cell-plating density on the steroidogenic activity of human cumulus cells

CYP17Genotypes Differ in Salivary 17-β Estradiol Levels: A Study Based on Hormonal Profiles from Entire Menstrual Cycles

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