The Mechanism of Androgen Actions in PCOS Etiology

Paris, Valentina Rodriguez; Bertoldo, Michael J.

doi:10.3390/medsci7090089

Cited by 58 publications

(45 citation statements)

References 83 publications

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“…There is no indication that IR is the primary driver of dyslipidemia neither in women with PCOS as suggested by the absence of effect of insulin sensitizing drugs 19 , nor in GK rats since they develop dyslipidemia prior to presenting IR 12 . The reason for the increase of LDL-C levels in women with PCOS is not yet clear but could be related to hyperandrogenism 21 .…”

Section: Resultsmentioning

confidence: 99%

The Goto-Kakizaki rat is a spontaneous prototypical rodent model of polycystic ovary syndrome

et al. 2021

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Polycystic ovary syndrome (PCOS) is characterized by an oligo-anovulation, hyperandrogenism and polycystic ovarian morphology combined with major metabolic disturbances. However, despite the high prevalence and the human and economic consequences of this syndrome, its etiology remains unknown. In this study, we show that female Goto-Kakizaki (GK) rats, a type 2 diabetes mellitus model, encapsulate naturally all the reproductive and metabolic hallmarks of lean women with PCOS at puberty and in adulthood. The analysis of their gestation and of their fetuses demonstrates that this PCOS-like phenotype is developmentally programmed. GK rats also develop features of ovarian hyperstimulation syndrome. Lastly, a comparison between GK rats and a cohort of women with PCOS reveals a similar reproductive signature. Thus, this spontaneous rodent model of PCOS represents an original tool for the identification of the mechanisms involved in its pathogenesis and for the development of novel strategies for its treatment.

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Section: Resultsmentioning

confidence: 99%

The Goto-Kakizaki rat is a spontaneous prototypical rodent model of polycystic ovary syndrome

et al. 2021

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“…Hyperandrogenism is a main feature of PCOS, occurring in 60-80% of the patient population (3). In ∼25-60% of PCOS women, adrenal androgens are present in excess, with dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and androstenedione the most common elevated androgens (4).…”

Section: Introductionmentioning

confidence: 99%

“…Due to its familial clustering and peripubertal onset, PCOS is characterized as an autosomal dominant genetic disease (9). Polycystic ovaries, testosterone levels, paternal metabolic syndrome (MBS) and type 2 diabetes mellitus (T2DM)-related defects in insulin secretion and action are all genetic factors for PCOS (4,(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Transgenerational Inheritance of Reproductive and Metabolic Phenotypes in PCOS Rats

Zhang

Dong

et al. 2020

Front. Endocrinol.

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Androgen exposure of female fetuses could be an important factor in the development of polycystic ovary syndrome (PCOS) in subsequent generations. The present study aimed to investigate the transgenerational effects of PCOS on the growth, reproduction, and metabolism of the first-and second-generation offspring in rats. Female F0 rats received excessive dehydroepiandrosterone (DHEA) exposure to establish PCOS or the same amount of vehicle as controls. These F0 females were crossed with normal males to obtain control (C) and DHEA (D) F1 offspring, whereas F2 offspring were obtained by inter-crossing between F1 rats for 4 groups: (1) C♂-C♀; (2) D♂-C♀; (3) C♂-D♀ and (4) D♂-D♀. Compared with control groups, F1 and F2 offspring with ancestral DHEA exposure showed higher body weight with increasing age. In addition, female F1 and F2 offspring with ancestral DHEA exposure exhibited PCOS-like reproductive and metabolic phenotypes, including disrupted estrous cycles and polycystic ovaries, as well as increased serum levels of testosterone, impaired glucose tolerance and widespread metabolic abnormalities. Male offspring with ancestral DHEA exposure exhibited lower quality of sperms. These findings confirm the negative effects of excessive androgen exposure of female fetuses on subsequent generations.

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“…Consequently, PCOS is now a growing global public health issue, and its prevention and management are of vital importance. Although the pathophysiology of PCOS is not completely understood, abnormal hormonal responses arbitrated by ovarian granulosa cells (GCs) during the progression of follicular development are considered to be the primary cause [3] . Moreover, accumulating evidence has highlighted a strong correlation between PCOS, dysregulation of glucose homeostasis, lactate accumulation, and abnormal modulation of glycolytic enzymes in GCs, mainly due to augmented energy demands and increased Androgen receptor (AR)-mediated androgen actions during folliculogenesis [3] , [4] , [5] .…”

mentioning

confidence: 99%

“…Although the pathophysiology of PCOS is not completely understood, abnormal hormonal responses arbitrated by ovarian granulosa cells (GCs) during the progression of follicular development are considered to be the primary cause [3] . Moreover, accumulating evidence has highlighted a strong correlation between PCOS, dysregulation of glucose homeostasis, lactate accumulation, and abnormal modulation of glycolytic enzymes in GCs, mainly due to augmented energy demands and increased Androgen receptor (AR)-mediated androgen actions during folliculogenesis [3] , [4] , [5] . In this context, the phosphoglycerate kinase 1 (PGK1), which catalyzes the conversion of 1,3-diphosphoglycerate into 3-phosphoglycerate, is known to be one of the most important ATP-generating enzymes in the glycolytic pathway [6] .…”

mentioning

confidence: 99%