Endocrinology: Iminunohistochemical study of steroidogenesis and cell proliferation in polycystic ovarian syndrome

Takayama, Ken‐ichi; Fukaya, Takao; Sasano, Hironobu; Funayama, Yukino; Suzuki, Takashi; Takaya, Risa; Wada, Yuichi; Yajima, Akira

doi:10.1093/oxfordjournals.humrep.a019405

Cited by 70 publications

(47 citation statements)

References 23 publications

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“…Decreased granulosa cell proliferation was also reported in bovine PCOS (Isobe & Yoshimura 2000). However, in studies carried out with PCOS women, either increased proliferation or no difference was found in granulosa cells of early antral follicles (4-8 mm diameter) in PCOS group compared with those in the control group (Takayama et al 1996, Stubbs et al 2007, Das et al 2008. The inconsistent results obtained from the human and rat may be due to the difference in the stage of the follicles examined.…”

Section: Discussionmentioning

confidence: 90%

“…Although altered cell proliferation in PCOS granulosa cells has been documented by a number of studies (Takayama et al 1996, Isobe & Yoshimura 2000, Stubbs et al 2007, Das et al 2008, Salvetti et al 2009, the underlying mechanism is not well understood. Herein, we have found that CFTR is downregulated in granulosa cells of PCOS rats, accompanied by downregulation of the pro-proliferative gene Pcna.…”

Section: Discussionmentioning

confidence: 99%

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Defective CFTR-regulated granulosa cell proliferation in polycystic ovarian syndrome

Chen¹,

Guo²,

Zhang³

et al. 2015

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Polycystic ovarian syndrome (PCOS) is one of the most frequent causes of female infertility, featured by abnormal hormone profile, chronic oligo/anovulation, and presence of multiple cystic follicles in the ovary. However, the mechanism underlying the abnormal folliculogenesis remains obscure. We have previously demonstrated that CFTR, a cAMP-dependent Cl K and HCO 3 K conducting anion channel, is expressed in the granulosa cells and its expression is downregulated in PCOS rat models and human patients. In this study, we aimed to investigate the possible involvement of downregulation of CFTR in the impaired follicle development in PCOS using two rat PCOS models and primary culture of granulosa cells. Our results indicated that the downregulation of CFTR in the cystic follicles was accompanied by reduced expression of proliferating cell nuclear antigen (PCNA), in rat PCOS models. In addition, knockdown or inhibition of CFTR in granulosa cell culture resulted in reduced cell viability and downregulation of PCNA. We further demonstrated that CFTR regulated both basal and FSH-stimulated granulosa cell proliferation through the HCO 3 K /sAC/PKA pathway leading to ERK phosphorylation and its downstream target cyclin D 2 (Ccnd2) upregulation. Reduced ERK phosphorylation and CCND2 were found in ovaries of rat PCOS model compared with the control. This study suggests that CFTR is required for normal follicle development and that its downregulation in PCOS may inhibit granulosa cell proliferation, resulting in abnormal follicle development in PCOS.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Defective CFTR-regulated granulosa cell proliferation in polycystic ovarian syndrome

Chen¹,

Guo²,

Zhang³

et al. 2015

Reproduction

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“…Some cases of hyperandrogenism have been reported in patients with aromatase deficiency (51,52). Immunohistochemical studies of polycystic ovaries could not detect aromatase in antral follicles of various sizes (53). On the other hand it has been found that granulosa cells from anovulatory polycystic ovaries are hyperresponsive to follicle-stimulating hormone (FSH) in vitro, displaying significantly greater oestradiol production than granulosa cells from normal ovaries, suggesting no functional deficiency of aromatase in polycystic ovaries (54).…”

Section: The Aromatase Gene (Cyp19)mentioning

confidence: 99%

The genetic basis of polycystic ovary syndrome

Xita

Georgiou

Tsatsoulis

2002

European Journal of Endocrinology

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Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The disorder is characterized by clinical features of hyperandrogenism, menstrual irregularities and often central obesity and hyperinsulinaemia. PCOS may increase the risk for infertility, type 2 diabetes mellitus, dyslipidaemia, cardiovascular disease and endometrial cancer, emphasizing the need for early diagnosis of the syndrome.The genetic basis of PCOS is unknown. There is a strong familial component but the mode of inheritance is uncertain and several candidate genes have been proposed to contribute to susceptibility. Not only genes involved in steroid hormone biosynthesis have been studied but also genes associated with the regulation of insulin secretion and action since hyperinsulinaemia is a characteristic of PCOS. So far there is evidence that INS VNTR (insulin variable number of tandem repeats) or CYP11a (cholesterol side chain cleavage) genes are associated with this syndrome. PCOS appears, however, to be an oligogenic disorder and more studies are necessary to define the genetic basis.

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“…It has previously been reported that alterations in the content of steroid hormones in the cystic ovaries of women [5,6], rat [7] and cow [8] was accompanied by changes in the expression and cellular distribution pattern of cholesterol side-chain cleavage cytochrome (P450 scc ), 3β-hydroxysteroid dehydrogenase (3β-HSD), 17,20-lyase, 20α-HSD and/or aromatase cytochrome (P450 arom ). Furthermore, our pilot study showed that dexamethasone (DXM) injections in gilts from day 16 of the first studied estrous cycle until day 9 of the second studied cycle, lead to changes in the of P450 scc , 3β-HSD and P450 arom protein expression, as well as in the content of progesterone (P 4 ), androgens and estrogens in ovarian structures [9].…”

Section: Introductionmentioning

confidence: 99%

Expression of steroidogenic enzymes in porcine polycystic ovaries.

Kozłowska

Majewski²,

Jana³

2009

Folia Histochem Cytobiol.

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Abstract:In the present study the expression pattern of the cholesterol side-chain cleavage cytochrome (P450 scc ), 3β-hydroxysteroid dehydrogenase (3β-HSD) and aromatase (P450 arom ) was analyzed in the health and polycystic ovaries of gilts by means of the Western blot and immunohistochemistry. The polycystic status of ovaries was induced by i.m. dexamethasone (DXM) injections on days 7-21 of the estrous cycle. Macroscopic observation of ovaries of DXM-treated gilts revealed the presence of cysts (1-2 cm in diameter, with a mean number of 7.0±1.2 per ovary), a decrease (P<0.05) in number of small follicles (1-3 mm in diameter), as well as the lack of medium-sized follicles (4-6 mm in diameter) and corpora lutea, as compared to the control animals. The expression of P450 scc (P<0.01), 3β-HSD (P<0.05) and P450 arom (P<0.001) proteins in the cysts was higher than in the medium-sized follicles of the control gilts. Moreover, DXM injections resulted also in an enhancement (P<0.05) in the level of P450 scc protein in the walls of small follicles as compared to the control gilts. Following DXM administration the immunoreactivity (IR) of P450 scc in the primordial follicles was lower than in the control group. Comparing to the control gilts, the reaction for this enzyme in DXM-treated animals was observed in secondary follicles, while for 3β-HSD, in primordial, primary, as well as secondary follicles. The immunostaining for P450 scc (theca cells) and P450 arom (granulosa cells) in the small follicles of the DXM-treated gilts were more prominent than those found in the gonads of control animals. However, IR for P450 scc was not found in the granulosa cells of small follicles in the gilts receiving DXM. The intensity of P450 scc and P450 arom labelling was distinctly enhanced in the cysts as compared to the medium follicles of the control animals. Furthermore, in contrary to the medium follicles of the control animals, faint IR for 3β -HSD was found in the granulosa cell layer of cysts. Our data revealed that both the expression of P450 scc , 3β-HSD and P450 arom and localization of these enzymes in polycystic ovaries were different from those, found under physiological conditions. These results suggested that above-mentioned enzymes may, by influencing the ovarian steroid synthesis, play an essential role in the creation and/or course of cystic ovarian disease.

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Endocrinology: Iminunohistochemical study of steroidogenesis and cell proliferation in polycystic ovarian syndrome

Cited by 70 publications

References 23 publications

Defective CFTR-regulated granulosa cell proliferation in polycystic ovarian syndrome

Defective CFTR-regulated granulosa cell proliferation in polycystic ovarian syndrome

The genetic basis of polycystic ovary syndrome

Expression of steroidogenic enzymes in porcine polycystic ovaries.

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