Pathological pulses in PCOS

Coyle, Clare; Campbell, Rebecca E.

doi:10.1016/j.mce.2019.110561

Cited by 65 publications

(48 citation statements)

References 118 publications

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“…There are not only changes in the reproductive system but also in the metabolic system. All of these results of animal models indicate that there should be strategies aimed simultaneously at multiple organs, in order to attenuate the developmental programming of PCOS [ 76 ].…”

Section: Potential Drug Targets and Active Substances In Novel Thementioning

confidence: 99%

In Search of New Therapeutics—Molecular Aspects of the PCOS Pathophysiology: Genetics, Hormones, Metabolism and Beyond

Wawrzkiewicz-Jałowiecka

Kowalczyk

Trybek

et al. 2020

IJMS

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In a healthy female reproductive system, a subtle hormonal and metabolic dance leads to repetitive cyclic changes in the ovaries and uterus, which make an effective ovulation and potential implantation of an embryo possible. However, that is not so in the case of polycystic ovary syndrome (PCOS), in which case the central mechanism responsible for entraining hormonal and metabolic rhythms during the menstrual cycle is notably disrupted. In this review we provide a detailed description of the possible scenario of PCOS pathogenesis. We begin from the analysis of how a set of genetic disorders related to PCOS leads to particular malfunctions at a molecular level (e.g., increased enzyme activities of cytochrome P450 (CYP) type 17A1 (17α-hydroxylase), 3β-HSD type II and CYP type 11A1 (side-chain cleavage enzyme) in theca cells, or changes in the expression of aquaporins in granulosa cells) and discuss further cellular- and tissue-level consequences (e.g., anovulation, elevated levels of the advanced glycation end products in ovaries), which in turn lead to the observed subsequent systemic symptoms. Since gene-editing therapy is currently out of reach, herein special emphasis is placed on discussing what kinds of drug targets and which potentially active substances seem promising for an effective medication, acting on the primary causes of PCOS on a molecular level.

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Section: Potential Drug Targets and Active Substances In Novel Thementioning

confidence: 99%

In Search of New Therapeutics—Molecular Aspects of the PCOS Pathophysiology: Genetics, Hormones, Metabolism and Beyond

Wawrzkiewicz-Jałowiecka

Kowalczyk

Trybek

et al. 2020

IJMS

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“…Ovarian dysfunction is thought to be caused by an impairment in the feedback loop of the steroid-hormone gonadotropin-releasing hormone (GnRH) produced in the hypothalamus. While there are other biologic systems and interconnected signaling networks also involved in the pathophysiology of PCOS, these latter networks may not be impaired in all affected women (6,8) In healthy women, the frequency of GnRH pulses in the hypothalamus regulate the pulsatile release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the anterior pituitary gland: faster frequencies favor LH secretion and slower frequencies favor FSH release. In turn, LH and FSH secretion regulates the production of follicles and gonadal steroids in the ovary.…”

Section: Theories About the Pathophysiology Of Pcosmentioning

confidence: 99%

“…In PCOS, this physiological feedback loop is compromised, resulting in hyperactivity of the hypothalamuspituitary-gonadal axis and an abnormally high LH : FSH ratio. This then impairs follicle generation in the ovary and interferes with the production of steroid hormones (6). Ovarian follicles remain in their immature state, a pre-ovulatory stage characterized by the cystic appearance of the ovary on ultrasound.…”

Section: Theories About the Pathophysiology Of Pcosmentioning

confidence: 99%

“…This leads to a state of hyperandrogenism (9). It is unclear whether the problem starts with a dysfunction in GnRH neurons in the hypothalamus or whether this occurs secondarily due to pathology of upstream neuronal systems (6).…”

Section: Theories About the Pathophysiology Of Pcosmentioning

confidence: 99%

“…There are several competing theories regarding the etiology of PCOS, but there is a consensus that the syndrome results from multiple causes. Significant interactions are likely among genetic and epigenetic factors, primary ovarian abnormalities, and neuroendocrine alterations (6). Recent evidence shows that neuroendocrine brain circuits, particularly the hypothalamic GnRH neuronal, are involved in the etiology of at least some forms of PCOS (7).…”

Section: Introductionmentioning

confidence: 99%

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Polycystic Ovary Syndrome and Psychotic Disorder

2020

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Polycystic ovary syndrome (PCOS), a disease that usually emerges during adolescence, is characterized by hormonal imbalance and ovarian dysfunction. The prevalence can vary between 5.6 to 21.3% in women and 6% in adolescent girls. This discrepancy is related to the population studied and the diagnostic criteria used. The underlying pathophysiology of PCOS is not fully understood, but it can lead to a number of co-morbidities, including hypertension, diabetes, dyslipidemia, and also, mental health disorders. Clinical and preclinical data indicate neuroendocrine involvement with dysfunction in gamma-Aminobutyric acid (GABA) signaling and neuronal androgen receptors that might reduce hypothalamic sensitivity and lead to an impairment of estradiol and progesterone feedback. Based on these assumptions, the aims of this paper are to review the association of PCOS and psychotic disorders in order to address the burden of women comorbid for both conditions.

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