scholarly journals A New Rat Model Exhibiting Both Ovarian and Metabolic Characteristics of Polycystic Ovary Syndrome

Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3781-3791 ◽  
Author(s):  
Louise Mannerås ◽  
Stefan Cajander ◽  
Agneta Holmäng ◽  
Zamira Seleskovic ◽  
Theodore Lystig ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Structural Changes ◽  
Polycystic Ovary ◽  
Female Rats ◽  
Polycystic Ovaries ◽  
Ovary Syndrome ◽  
Continuous Administration ◽  
Metabolic Characteristics ◽  
Theca Interna

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity, and insulin resistance. However, its etiology is unclear, and its management is often unsatisfactory or requires a diversified approach. Here, we describe a new rat PCOS model, the first to exhibit both ovarian and metabolic characteristics of the syndrome. Female rats received the nonaromatizable androgen dihydrotestosterone (DHT) or the aromatase inhibitor letrozole by continuous administration, beginning before puberty, to activate androgen receptors. Adult DHT rats had irregular cycles, polycystic ovaries characterized by cysts formed from atretic follicles, and a diminished granulosa layer. They also displayed metabolic features, including increased body weight, increased body fat, and enlarged mesenteric adipocytes, as well as elevated leptin levels and insulin resistance. All letrozole rats were anovulatory and developed polycystic ovaries with structural changes strikingly similar to those in human PCOS. Our findings suggest that the formation of a “hyperplastic” theca interna reflects the inclusion of luteinized granulosa cells in the cyst wall rather than true hyperplasia. We conclude that the letrozole model is suitable for studies of the ovarian features of human PCOS, while the DHT model is suitable for studies of both ovarian and metabolic features of the syndrome.

scholarly journals Continuous Administration of a P450 Aromatase Inhibitor Induces Polycystic Ovary Syndrome with a Metabolic and Endocrine Phenotype in Female Rats at Adult Age

Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 434-445 ◽  
Author(s):  
Manuel Maliqueo ◽  
Miao Sun ◽  
Julia Johansson ◽  
Anna Benrick ◽  
Fernand Labrie ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Female Rats ◽  
Control Group ◽  
Ovary Syndrome ◽  
Continuous Administration ◽  
P450 Aromatase ◽  
Fat Depots ◽  
Estrogen Synthesis

Studying the mechanisms for the complex pathogenesis of polycystic ovary syndrome (PCOS) requires animal models with endocrine, reproductive, and metabolic features of the syndrome. Hyperandrogenism seems to be a central factor in PCOS, leading to anovulation and insulin resistance. In female rats, continuous administration of letrozole, a nonsteroidal inhibitor of P450 aromatase, at 400 μg/d starting before puberty induces hyperandrogenemia and reproductive abnormalities similar to those in women with PCOS. However, despite high circulating testosterone levels, these rats do not develop metabolic abnormalities, perhaps because of their supraphysiological testosterone concentrations or because estrogen synthesis is completely blocked in insulin-sensitive tissues. To test the hypothesis that continuous administration of lower doses of letrozole starting before puberty would result in both metabolic and reproductive phenotypes of PCOS, we performed a 12-wk dose-response study. At 21 d of age, 46 female Wistar rats were divided into two letrozole groups (100 or 200 μg/d) and a control group (placebo). Both letrozole doses resulted in increased body weight, inguinal fat accumulation, anovulation, larger ovaries with follicular atresia and multiples cysts, endogenous hyperandrogemia, and lower estrogen levels. Moreover, rats that received 200 μg/d had insulin resistance and enlarged adipocytes in inguinal and mesenteric fat depots, increased circulating levels of LH, decreased levels of FSH, and increased ovarian expression of Cyp17a1 mRNA. Thus, continuous administration of letrozole, 200 μg/d, to female rats for 90 d starting before puberty results in a PCOS model with reproductive and metabolic features of the syndrome.

scholarly journals Body composition, metabolic characteristics, and insulin resistance in obese and nonobese women with polycystic ovary syndrome

2019 ◽  
Vol 12 (2) ◽  
pp. 78
Author(s):  
ThomasV Paul ◽  
Anil Satyaraddi ◽  
KripaElizabeth Cherian ◽  
Nitin Kapoor ◽  
AleyammaThaiparambil Kunjummen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Composition ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Metabolic Characteristics

scholarly journals An adolescent with polycystic ovary syndrome

2006 ◽  
Vol 155 (suppl_1) ◽  
pp. S149-S152 ◽  
Author(s):  
Marja Ojaniemi ◽  
Michel Pugeat
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Polycystic Ovaries ◽  
Ovary Syndrome ◽  
The Metabolic Syndrome ◽  
Menstrual Irregularities ◽  
Term Basis

Polycystic ovary syndrome (PCOS) is a common clinical condition that manifests during adolescence with menstrual irregularities, acne, and hirsutism. As these symptoms are frequently observed in healthy teenagers, it can be difficult to recognize PCOS. Establishment of hyperandrogenism, polycystic ovaries, and identifying a metabolic disorder are required for the management of PCOS in a teenager. The underlying defects in PCOS are still unclear; however, insulin resistance and the metabolic syndrome are common in both obese and non-obese PCOS patients, so that the evaluation of glucose tolerance is recommended. More than 50% of PCOS patients are overweight or obese, and will benefit from an increase in physical activity and weight loss. Metformin is a treatment option that requires further investigation before being recommended on a long-term basis.

scholarly journals Diet-induced obesity exacerbates metabolic and behavioral effects of polycystic ovary syndrome in a rodent model

2015 ◽  
Vol 308 (12) ◽  
pp. E1076-E1084 ◽  
Author(s):  
Ilana B. Ressler ◽  
Bernadette E. Grayson ◽  
Yvonne M. Ulrich-Lai ◽  
Randy J. Seeley
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Forced Swim Test ◽  
Rodent Model ◽  
Reproductive Age ◽  
Female Rats ◽  
Ovary Syndrome ◽  
Stress Responsivity

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Although a comorbidity of PCOS is obesity, many are lean. We hypothesized that increased saturated fat consumption and obesity would exacerbate metabolic and stress indices in a rodent model of PCOS. Female rats were implanted with the nonaromatizable androgen dihydrotestosterone (DHT) or placebo pellets prior to puberty. Half of each group was maintained ad libitum on either a high-fat diet (HFD; 40% butter fat calories) or nutrient-matched low-fat diet (LFD). Irrespective of diet, DHT-treated animals gained more body weight, had irregular cycles, and were glucose intolerant compared with controls on both diets. HFD/DHT animals had the highest levels of fat mass and insulin resistance. DHT animals demonstrated increased anxiety-related behavior in the elevated plus maze by decreased distance traveled and time in the open arms. HFD consumption increased immobility during the forced-swim test. DHT treatment suppressed diurnal corticosterone measurements in both diet groups. In parallel, DHT treatment significantly dampened stress responsivity to a mild stressor. Brains of DHT animals showed attenuated c-Fos activation in the ventromedial hypothalamus and arcuate nucleus; irrespective of DHT-treatment, however, all HFD animals had elevated hypothalamic paraventricular nucleus c-Fos activation. Whereas hyperandrogenism drives overall body weight gain, glucose intolerance, anxiety behaviors, and stress responsivity, HFD consumption exacerbates the effect of androgens on adiposity, insulin resistance, and depressive behaviors.

scholarly journals Specificities of the treatment for polycystic ovary syndrome and metabolic syndrome

2020 ◽  
Vol 3 (4) ◽  
pp. 254-259
Author(s):  
I.Yu. Il’ina ◽  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Polycystic Ovary Syndrome ◽  
Metabolic Disorders ◽  
Negative Impact ◽  
Polycystic Ovary ◽  
Cardiovascular Complications ◽  
Polycystic Ovaries ◽  
Ovary Syndrome ◽  
Psychic Disorders

This paper discusses polycystic ovary syndrome (PCOS), a common endocrine disorder characterized by hirsutism, anovulation, and polycystic ovaries. Insulin resistance which is considered the major causative factor for both PCOS and metabolic syndrome is emphasized. The early diagnosis of metabolic disorders which increase the risk of cardiovascular complications and the complications of pregnancy (including gestational diabetes and hypertension which may result in preeclampsia and placental abruption) is of particular importance. The presence of metabolic syndrome in PCOS is associated with poor prognosis in terms of fertility and has a negative impact on the outcomes of in vitro fertilization in infertile women with PCOS. When describing treatment approaches, the role of metformin, inositol, folates, vitamin D, and statins in treating metabolic disorders in PCOS and metabolic syndrome, reducing the risks of cardiovascular complications, and realizing fertile function is highlighted. The course of PCOS is complicated by psychic disorders (i.e., depression, anxiety, bipolar disorder, or eating disorders) which are common in these women and should be considered when prescribing medications. KEYWORDS: polycystic ovary syndrome, insulin resistance, infertility, metabolic syndrome, cardiovascular complications, inositol, folates. FOR CITATION: Il’ina I.Yu. Specificities of the treatment for polycystic ovary syndrome and metabolic syndrome. Russian Journal of Woman and Child Health. 2020;3(4):254–259. DOI: 10.32364/2618-8430-2020-3-4-254-259.

scholarly journals Effects of Metformin on Reproductive, Endocrine, and Metabolic Characteristics of Female Offspring in a Rat Model of Letrozole-induced Polycystic Ovarian Syndrome With Insulin Resistant

2020 ◽  
Author(s):  
Yidong Xie ◽  
Li Xiao ◽  
Xiaohan Shi ◽  
Yifan Zhao ◽  
Xiaohong Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Rat Model ◽  
Wistar Rats ◽  
Polycystic Ovary ◽  
Female Offspring ◽  
Ovary Syndrome ◽  
Metabolic Characteristics ◽  
Reproductive Endocrine ◽  
The Impact

Abstract Background: Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder that has many characteristic features including hyperandrogenemia, insulin resistance and obesity. The beneficial effects of metformin on reproduction, metabolism and endocrine, especially with the capacity to ameliorate insulin resistance (IR) in polycystic ovary syndrome (PCOS), place it as a good alternative for its widely prescribed, but its association with PCOS offspring remains uncertain. We aim to investigate the impact of metformin on reproductive, endocrine and metabolic characteristics in female offspring born to letrozole-induced PCOS-IR rats.Methods: 45 female wistar rats were implanted with letrozole-continuous-release pellets or placebo, subsequently treated with metformin or vehicle control, then mated with healthy male wistar rats. Estrous cycle, endocrine hormone profile, fasting insulin measurements and glucose tolerance test have been investigated and the expression of INSR in pancreas, FSHR and LHCGR in ovaries have been analyzed with Quantitative Real-time Polymerase Chain Reaction and Western Blotting assay.Results: Decreased conception rate and increased multiple pregnancy rates were found in PCOS-IR rats, which significantly improved after metformin treatment. Metformin significantly decreased the risk of body weight gain and increased INSR expression of pancreas in female F1 offspring in PCOS-IR rats. Decreased FSHR and increased LHCGR expressions in ovary were observed in female F1 rats of PCOS-IR and PCOS-IR+Met group. Nevertheless, there were no significant differences of INSR, FSHR and LHCGR expressions in female F2 offspring of PCOS-IR rats, as well as other PCOS phenotypes.Conclusions: The current study indicates that widespread reproductive, endocrine and metabolic changes in letrozole induced PCOS-IR rat model, but those PCOS phenotypes could not be inherit to offspring generations stably. Metformin may contribute to improve obesity, hyperinsulinemia and insulin resistance of female F1 offspring in PCOS-IR. The results of this study can be used as a theoretical basis for supporting metformin-using in the treatment of PCOS-IR patients.

scholarly journals 5α-dihydrotestosterone treatment induces metabolic changes associated with polycystic ovary syndrome without interfering with hypothalamic leptin and glucocorticoid signaling

2016 ◽  
Vol 68 (3) ◽  
pp. 473-481
Author(s):  
Marina Nikolic ◽  
Natasa Velickovic ◽  
Ana Djordjevic ◽  
Biljana Bursac ◽  
Djuro Macut ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Day Treatment ◽  
Reproductive Age ◽  
Female Rats ◽  
Leptin Resistance ◽  
Polycystic Ovaries ◽  
Metabolic Disturbances ◽  
Inflammatory Signaling ◽  
Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is a heterogenous disorder, with hyperandrogenism, chronic anovulation and polycystic ovaries as basic characteristics, and associated metabolic syndrome features. Increased secretion of leptin and leptin resistance are common consequences of obesity. Leptin is a hormone with anorexigenic effects in the hypothalamus. Its function in the regulation of energy intake and consumption is antagonized by glucocorticoids. By modulating leptin signaling and inflammatory processes in the hypothalamus, glucocorticoids can contribute to the development of metabolic disturbances associated with central energy disbalance. The aim of the study was to examine the relationship between hypothalamic leptin, glucocorticoid and inflammatory signaling in the development of metabolic disturbances associated with PCOS. The study was conducted on an animal model of PCOS generated by a continual, 90-day treatment of female rats with 5?-dihydrotestosterone (DHT). The model exhibited all key reproductive and metabolic features of the syndrome. mRNA and/or protein levels of the key components of hypothalamic glucocorticoid, leptin and inflammatory pathways, presumably contributing to energy disbalance in DHT-treated female rats, were measured. The results indicated that DHT treatment led to the development of hyperphagia and hyperleptinemia as metabolic features associated with PCOS. However, these metabolic disturbances could not be ascribed to changes in hypothalamic leptin, glucocorticoid or inflammatory signaling pathways in DHT-treated rats.

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