ArticleThe European journal of neuroscience2016
Prenatal testosterone exposure decreases colocalization of insulin receptors in kisspeptin/neurokinin B/dynorphin and agouti-related peptide neurons of the adult ewe.
Article in The European journal of neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Sexual dimorphism in the development and function of the melanocortin system.Reviews in endocrine & metabolic disorders · 2026Review
- Exploring the Role of Kisspeptin in Polycystic Ovary Syndrome and Its Associated Pregnancy Complications.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- Brain-Specific Gata4 Downregulation in Greywick Female Mice Models the Metabolic Subtype of Polycystic Ovary Syndrome.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Altered expression of kisspeptin, dynorphin, and related neuropeptides in polycystic ovary syndrome: A cross-sectional study.International journal of reproductive biomedicine · 2024Article
- Malnutrition alters protein expression of KNDy neuropeptides in the arcuate nucleus of mature ewes.Frontiers in physiology · 2024Article
- Alterations in Appetite-Regulating Hormones in Girls with Central Early or Precocious Puberty.Nutrients · 2023Review
- Potential for NPY receptor-related therapies for polycystic ovary syndrome: an updated review.Hormones (Athens, Greece) · 2023Review
- Review
- Review
- The impact of undernutrition on KNDy (kisspeptin/neurokinin B/dynorphin) neurons in female lambs.Journal of neuroendocrinology · 2022Article
- Transcriptomic Changes of Photoperiodic Response in the Hypothalamus Were Identified in Ovariectomized and Estradiol-Treated Sheep.Frontiers in molecular biosciences · 2022Article
- EDCs Reorganize Brain-Behavior Phenotypic Relationships in Rats.Journal of the Endocrine Society · 2021Article
- Undernutrition reduces kisspeptin and neurokinin B expression in castrated male sheep.Reproduction & fertility · 2020Article
- Animal Models to Understand the Etiology and Pathophysiology of Polycystic Ovary Syndrome.Endocrine reviews · 2020Review
- Developmental programming of insulin resistance: are androgens the culprits?The Journal of endocrinology · 2020Review
- The impact of androgen actions in neurons on metabolic health and disease.Molecular and cellular endocrinology · 2018Review
- Three-dimensional imaging of KNDy neurons in the mammalian brain using optical tissue clearing and multiple-label immunocytochemistry.Scientific reports · 2018Article
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Insulin serves as a link between the metabolic and reproductive systems, communicating energy availability to the hypothalamus and enabling reproductive mechanisms. Adult Suffolk ewes prenatally exposed to testosterone (T) display an array of reproductive and metabolic dysfunctions similar to those seen in women with polycystic ovarian syndrome (PCOS), including insulin resistance. Moreover, prenatal T treatment alters neuropeptide expression in KNDy (co-expressing kisspeptin, neurokinin B/dynorphin) and agouti-related peptide (AgRP) neurons in the arcuate nucleus, two populations that play key roles in the control of reproduction and metabolism, respectively. In this study, we determined whether prenatal T treatment also altered insulin receptors in KNDy and AgRP neurons, as well as in preoptic area (POA) kisspeptin, pro-opiomelanocortin (POMC), and gonadotropin-releasing hormone (GnRH) neurons of the adult sheep brain. Immunofluorescent detection of the beta subunit of insulin receptor (IRβ) revealed that KNDy, AgRP and POMC neurons, but not GnRH or POA kisspeptin neurons, colocalize IRβ in control females. Moreover, prenatal T treatment decreased the percentage of KNDy and AgRP neurons that colocalized IRβ, consistent with reduced insulin sensitivity. Administration of the anti-androgen drug, Flutamide, during prenatal T treatment, prevented the reduction in IRβ colocalization in AgRP, but not in KNDy neurons, suggesting that these effects are programmed by androgenic and oestrogenic actions, respectively. These findings provide novel insight into the effects of prenatal T treatment on hypothalamic insulin sensitivity and raise the possibility that decreased insulin receptors, specifically within KNDy and AgRP neurons, may contribute to the PCOS-like phenotype of this animal model.
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Registered trials
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