The neuroendocrine genesis of polycystic ovary syndrome: A role for arcuate nucleus GABA neurons

•The common endocrine disorder polycystic ovary syndrome (PCOS) may be, in part, a disease of the brain.•Androgen actions leading to disrupted progesterone signalling is implicated in impaired negative feedback in PCOS.•Prenatal androgen exposure recapitulates the neuroendocrine features of PCOS in...

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Bibliographic Details
Published in:The Journal of steroid biochemistry and molecular biology 2016-06, Vol.160, p.106-117
Main Authors: Moore, Aleisha M., Campbell, Rebecca E.
Format: Article
Language:English
Subjects:
Androgens - metabolism
Animals
Female
Fertility
GABAergic Neurons - metabolism
GABAergic Neurons - pathology
Gonadotropin-releasing hormone
Humans
Hypothalamo-Hypophyseal System - metabolism
Hypothalamo-Hypophyseal System - pathology
Mouse
Negative feedback
Pituitary-Adrenal System - metabolism
Pituitary-Adrenal System - pathology
Polycystic Ovary Syndrome - metabolism
Polycystic Ovary Syndrome - pathology
Prenatal androgen model
Progesterone - metabolism
Progesterone receptor
Signal Transduction
Tract-tracing
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Summary:•The common endocrine disorder polycystic ovary syndrome (PCOS) may be, in part, a disease of the brain.•Androgen actions leading to disrupted progesterone signalling is implicated in impaired negative feedback in PCOS.•Prenatal androgen exposure recapitulates the neuroendocrine features of PCOS in animal models.•Arcuate nucleus GABA neurons are implicated in mediating the neuroendocrine impairments of PCOS. Polycystic ovary syndrome (PCOS) is a prevalent and distressing endocrine disorder lacking a clearly identified aetiology. Despite its name, PCOS may result from impaired neuronal circuits in the brain that regulate steroid hormone feedback to the hypothalamo–pituitary–gonadal axis. Ovarian function in all mammals is controlled by the gonadotropin-releasing hormone (GnRH) neurons, a small group of neurons that reside in the pre-optic area of the hypothalamus. GnRH neurons drive the secretion of the gonadotropins from the pituitary gland that subsequently control ovarian function, including the production of gonadal steroid hormones. These hormones, in turn, provide important feedback signals to GnRH neurons via a hormone sensitive neuronal network in the brain. In many women with PCOS this feedback pathway is impaired, resulting in the downstream consequences of the syndrome. This review will explore what is currently known from clinical and animal studies about the identity, relative contribution and significance of the individual neuronal components within the GnRH neuronal network that contribute to the pathophysiology of PCOS. We review evidence for the specific neuronal pathways hypothesised to mediate progesterone negative feedback to GnRH neurons, and discuss the potential mechanisms by which androgens may evoke disruptions in these circuits at different developmental time points. Finally, this review discusses data providing compelling support for disordered progesterone-sensitive GABAergic input to GnRH neurons, originating specifically within the arcuate nucleus in prenatal androgen induced forms of PCOS.
ISSN:0960-0760
1879-1220
DOI:10.1016/j.jsbmb.2015.10.002