The Insulin-Related Ovarian Regulatory System in Health and Disease

Poretsky, Leonid; Cataldo, Nicholas A.; Rosenwaks, Zev; Giudice, Linda C.

doi:10.1210/edrv.20.4.0374

Cited by 626 publications

(328 citation statements)

References 609 publications

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“…These observations suggest that the ovarian component of the IR syndrome, quite unlike fatty liver and DL, do not require intact INSR function, although they do require severe hyperinsulinaemia. These findings may be reconciled by hypothesising that very high levels of insulin enhance signalling through the IGF receptor, in keeping with a large body of evidence for an important role for IGFs in follicular maturation (88,89). PCOS is reported to be common in premenopausal women with acromegaly (90); however, it is not usually as severe as that seen in the context of severe IR.…”

Section: European Journal Of Endocrinologymentioning

confidence: 97%

EJE PRIZE 2015: How does insulin resistance arise, and how does it cause disease? Human genetic lessons

Semple¹

2016

European Journal of Endocrinology

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Insulin orchestrates physiological responses to ingested nutrients; however, although it elicits widely ramifying metabolic and trophic responses from diverse tissues, 'insulin resistance (IR)', a pandemic metabolic derangement commonly associated with obesity, is usually defined solely by blunting of insulin's hypoglycaemic effect. Recent study of monogenic forms of IR has established that biochemical subphenotypes of IR exist, clustering into those caused by primary disorders of adipose tissue and those caused by primary defects in proximal insulin signalling. IR is often first recognised by virtue of its associated disorders including type 2 diabetes, dyslipidaemia (DL), fatty liver and polycystic ovary syndrome (PCOS). Although these clinically observed associations are confirmed by cross-sectional and longitudinal population-based studies, causal relationships among these phenomena have been more difficult to establish. Single gene IR is important to recognise in order to optimise clinical management and also permits testing of causal relationships among components of the IR syndrome using the principle of Mendelian randomisation. Thus, where a precisely defined genetic defect is identified that directly produces one component of the syndrome, then phenomena that are causally linked to that component should be seen. Where this is not the case, then a simple causal link is refuted. This article summarises known forms of monogenic severe IR and considers the lessons to be learned about the pathogenic mechanisms both upstream from common IR and those downstream linking it to disorders such as DL, fatty liver, PCOS and cancer.

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Section: European Journal Of Endocrinologymentioning

confidence: 97%

EJE PRIZE 2015: How does insulin resistance arise, and how does it cause disease? Human genetic lessons

Semple¹

2016

European Journal of Endocrinology

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“…Hyperinsulinemia might facilitate pubertal weight gain and growth as well as increase luteinizing hormone-stimulated ovarian and adrenal steroidogenesis [72]. …”

Section: Sex Hormones and Growth During Pubertymentioning

confidence: 99%

Putative Effects of Obesity on Linear Growth and Puberty

Shalitin

Kieß²

2017

Horm Res Paediatr

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Childhood obesity is a major public health problem that has grown to epidemic proportions throughout the world. Obesity is influenced by genetic and environmental factors. The nutritional status plays an important role in growth and body weight regulation. Excess adiposity during childhood can affect the process of growth and puberty. Obese children are frequently tall for their age, with accelerated epiphyseal growth plate maturation despite low growth hormone levels. Several regulatory hormones may affect the process of linear growth in the constellation of obesity, as high levels of insulin and leptin are observed in obese children. Leptin can act as a skeletal growth factor, with a direct effect on skeletal growth centers. The finding that overweight children, especially girls, tend to mature earlier than lean children has led to the hypothesis that the degree of body fatness may trigger the neuroendocrine events that lead to the onset of puberty. Leptin receptors have been identified in the hypothalamus, as well as in gonadotrope cells, ovarian follicular cells, and Leydig cells. The increased leptin and androgen levels seen in obese children may be implicated in their earlier onset of puberty and accelerated pubertal growth. This review is focused on the interaction between childhood obesity and growth and pubertal processes.

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“…Although the pathophysiology of PCOS is not yet completely understood, the key factor is androgen excess, which is associated with insulin resistance (Dunaif 1997;Poretsky et al 1999) and hypothalamus−pituitary−ovary axis disorders, which results in an elevation of serum luteinizing hormone (LH) levels (Blank et al 2006;Taylor et al 1997). Furthermore, owing to its heterogeneous pathophysiology, various phenotypes of PCOS have been observed.…”

Section: Introductionmentioning

confidence: 99%

Increase of kisspeptin-positive cells in the hypothalamus of a rat model of polycystic ovary syndrome

et al. 2016

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Kisspeptin, a hypothalamic neuropeptide, is expressed in the arcuate nucleus (ARC) that is considered as the center of the gonadotropin-releasing hormone (GnRH)-pulse generator. We hypothesized that kisspeptin expressed in the ARC is implicated in the disturbance of the hypothalamus-pituitary-ovary axis observed in polycystic ovary syndrome (PCOS). To test this hypothesis, we evaluated the hormonal profiles, luteinizing hormone (LH) pulse, and ARC kisspeptin immunoreactivity in a PCOS rat model using the anti-progestin RU486. We found an alteration of the LH pulse, including a trend towards an increased mean LH concentration and area under the curve, and a significant upregulation of the mean LH pulse amplitude. Additionally, a higher number of kisspeptin-positive cells was observed in the ARC of RU486-treated rats than in the ARC of intact rats. These results suggest the possible involvement of hypothalamic kisspeptin in the hypothalamus-pituitary-ovary axis and therefore, in PCOS pathophysiology.

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The Insulin-Related Ovarian Regulatory System in Health and Disease

Cited by 626 publications

References 609 publications

EJE PRIZE 2015: How does insulin resistance arise, and how does it cause disease? Human genetic lessons

EJE PRIZE 2015: How does insulin resistance arise, and how does it cause disease? Human genetic lessons

Putative Effects of Obesity on Linear Growth and Puberty

Increase of kisspeptin-positive cells in the hypothalamus of a rat model of polycystic ovary syndrome

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