Rats with steroid-induced polycystic ovaries develop hypertension and increased sympathetic nervous system activity

Stener-Victorin, Elisabet; Ploj, Karolina; Larsson, Bo; Holmäng, Agneta

doi:10.1186/1477-7827-3-44

Cited by 77 publications

(35 citation statements)

References 54 publications

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“…While L had no significant effect from this perspective, in the EV group we observed an increased level of fasting glycemia. This result was consistent with Letrozole vs estradiol valerate PCOS in rats our previous study (Dȃneasȃ et al 2014), but contrary to the results obtained in literature (Stener-Victorin et al 2005, Dikmen et al 2012. Slightly elevated glycemic levels are able to promote mitochondrial reactive oxygen species (ROS) production (Nishikawa et al 2000).…”

Section: Discussionsupporting

confidence: 83%

Letrozole vs estradiol valerate induced PCOS in rats: glycemic, oxidative and inflammatory status assessment

et al. 2016

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The objective of our study was to investigate glycemic, oxidative/antioxidative and inflammatory status in letrozole and estradiol valerate induced polycystic ovarian syndrome (PCOS) models. Sixty adult female Wistar rats were divided into four groups: L (0.2 mg letrozole/0.5 ml carboxymethyl cellulose (CMC), daily for 30 days), the control group C L , EV (one i.m. injection of 5 mg EV/0.5 ml sesame oil) and its corresponding control group C EV . After 30 days, ovarian morphology was assessed through ultrasound, serum free testosterone was determined, and an oral glucose tolerance test was performed. Blood, muscle, liver and periovarian adipose tissue (POAT) were collected for oxidative/antioxidative and inflammatory status evaluation. Free testosterone was increased only in the L group, while fasting glycemia was higher in the EV group. Both L and EV led to a significantly decreased level of muscle malondialehyde (MDA) and liver glutathione peroxidase (GPx) activity, while in POAT, MDA level diminished and GPx activity increased. The only difference between the two protocols was in muscle, where after L administration, GPx activity was significantly lower. Implementation of both protocols resulted in an increased expression of pNFKB in muscle, liver and POAT. The expression of monocyte chemoattractant protein 1 (MCP1) increased in liver and POATafter L administration, while in the EV group, MCP1 and STAT3 decreased in POAT. Our study shows that both protocols are characterized by an inflammatory environment in the usually insulin resistant tissues of human PCOS, without generating oxidative stress. In addition, EV has mild metabolic effects and unexpected interference with MCP1 expression in POAT, which require further investigation.

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Section: Discussionsupporting

confidence: 83%

Letrozole vs estradiol valerate induced PCOS in rats: glycemic, oxidative and inflammatory status assessment

et al. 2016

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“…Women with PCOS have increased sympathetic activity 28 . Manneras and colleagues and Stener-Victorin also found that sympathetic activity was increased in a Wistar model of PCOS 12, 16 . It is not clear whether increased sympathetic activity contributes to the elevated blood pressure in HAF rats..…”

Section: Discussionmentioning

confidence: 88%

“…Models of estradiol valerate-induced PCO have been described, but plasma testosterone levels were lower in the treated rats than controls, and the treated rats did not exhibit insulin sensitivity 12 . Shi and colleagues also reported that the JCR:LA-cp rat develops features of PCOS, such as obesity, insulin resistance, elevated serum testosterone levels, but this model has a defect in the ObR gene leading to loss of leptin receptor function 13 .…”

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confidence: 99%

Cardiovascular-Renal and Metabolic Characterization of a Rat Model of Polycystic Ovary Syndrome

et al. 2011

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Background Polycystic ovary syndrome (PCOS) is the most common reproductive dysfunction in premenopausal women. PCOS is also associated with increased risk of cardiovascular disease at the time of PCOS and later in life. Hypertension, a common finding in women with PCOS, is a leading risk factor for cardiovascular disease. The mechanisms responsible for hypertension in women with PCOS has not been elucidated. Objectives To characterize the cardiovascular-renal consequences of hyperandrogenemia in a female rat model. Methods Female Sprague Dawley rats, aged 4–6 weeks, were implanted with DHT or placebo pellets lasting 90 days. Following 10–12 weeks, blood pressure (by radiotelemetry), renal function (glomerular filtration rate, morphology, protein and albumin excretion), metabolic parameters (plasma insulin, glucose, leptin, cholesterol, oral glucose tolerance test), inflammation (plasma TNF-α), oxidative stress (mRNA expression of NADPH oxidase subunits, p22phox, p47phox, gp91phox, and NOX4, nitrate/nitrite excretion), and mRNA expression of components of the renin-angiotensin system (RAS) (angiotensinogen, angiotensin-I-converting enzyme (ACE), AT1 receptor) were determined. Results Plasma DHT was increased 3-fold in hyperandrogenemic female 1 rats, whereas plasma estradiol levels were not different compared to control females. HAF rats exhibited estrus cycle dysfunction. They also had increased food intake and body weight, increased visceral fat, glomerular filtration rate, renal injury, insulin resistance and metabolic dysfunction, oxidative stress, and increased expression of angiotensinogen and ACE and reduced AT1 receptor expression. Conclusions The HAF rat is a unique model that exhibits many of the characteristics of PCOS in women and is a useful model in order to study the mechanisms responsible for hypertension.

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“…Furthermore, it is clear that both androgenic and oestrogenic mechanisms are involved in the programming of the PCOS phenotype as in the prenatally androgenised sheep model testosterone, but DHT does not induce polycystic ovaries and abnormal antral follicle morphology and does not increase follicle activation (West et al 2001, Smith et al 2009). In saying this, further support for AR-mediated actions playing a predominant role in the manifestation of PCOS traits comes from the findings that exposure of rats to E 2 valerate can induce anovulation and polycystic ovaries, but it fails to provoke the breadth of features induced by androgens including LH hypersecretion, hyperandrogenism, obesity and alterations in glucose and insulin sensitivity (Brawer et al 1978, Stener-Victorin et al 2005. Furthermore, differences in the timing of the elevated androgen exposure have recently been put forward as a key determinant in the development of various characteristics of PCOS.…”

Section: Dihydrotestosteronementioning

confidence: 99%

Role of androgens in normal and pathological ovarian function

Walters

2015

Reproduction

138

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Androgens mediate their actions via the androgen receptor (AR), a member of the nuclear receptor superfamily. AR-mediated androgen action is essential in male reproductive development and function; however, only in the last decade has the suspected but unproven role for AR-mediated actions in female reproduction been firmly established. Deciphering the specific roles and precise pathways by which AR-mediated actions regulate ovarian function has been hindered by confusion on how to interpret results from pharmacological studies using androgens that can be converted into oestrogens, which exert actions via the oestrogen receptors. The generation and analysis of global and cell-specific female Ar knockout mouse models have deduced a role for AR-mediated actions in regulating ovarian function, maintaining female fertility, and have begun to unravel the mechanisms by which AR-mediated androgen actions regulate follicle health, development and ovulation. Furthermore, observational findings from human studies and animal models provide substantial evidence to support a role for AR-mediated effects not only in normal ovarian function but also in the development of the frequent ovarian pathological disorder, polycystic ovarian syndrome (PCOS). This review focuses on combining the findings from observational studies in humans, pharmacological studies and animal models to reveal the roles of AR-mediated actions in normal and pathological ovarian function. Together these findings will enable us to begin understanding the important roles of AR actions in the regulation of female fertility and ovarian ageing, as well as providing insights into the role of AR actions in the androgen-associated reproductive disorder PCOS.Reproduction (2015) 149 R193-R218

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Rats with steroid-induced polycystic ovaries develop hypertension and increased sympathetic nervous system activity

Abstract: Background: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, abdominal obesity, hyperandrogenism, hypertension, and insulin resistance.

Cited by 77 publications

References 54 publications

Letrozole vs estradiol valerate induced PCOS in rats: glycemic, oxidative and inflammatory status assessment

Letrozole vs estradiol valerate induced PCOS in rats: glycemic, oxidative and inflammatory status assessment

Cardiovascular-Renal and Metabolic Characterization of a Rat Model of Polycystic Ovary Syndrome

Role of androgens in normal and pathological ovarian function

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