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Prenatal testosterone exposure decreases colocalization of insulin receptors in kisspeptin/neurokinin B/dynorphin and agouti‐related peptide neurons of the adult ewe
Author(s) -
Cernea Maria,
Phillips Rebecca,
Padmanabhan Vasantha,
Coolen Lique M.,
Lehman Michael N.
Publication year - 2016
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13373
Subject(s) - kisspeptin , endocrinology , medicine , neurokinin b , polycystic ovary , hypothalamus , biology , arcuate nucleus , testosterone (patch) , gonadotropin releasing hormone , dynorphin , androgen , androgen receptor , neuropeptide , insulin , receptor , insulin resistance , hormone , luteinizing hormone , substance p , prostate cancer , cancer , opioid , opioid peptide
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 KND y (co‐expressing kisspeptin, neurokinin B/dynorphin) and agouti‐related peptide (Ag RP ) 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 KND y and Ag RP neurons, as well as in preoptic area ( POA ) kisspeptin, pro‐opiomelanocortin ( POMC ), and gonadotropin‐releasing hormone (Gn RH ) neurons of the adult sheep brain. Immunofluorescent detection of the beta subunit of insulin receptor ( IR β) revealed that KND y, Ag RP and POMC neurons, but not Gn RH or POA kisspeptin neurons, colocalize IR β in control females. Moreover, prenatal T treatment decreased the percentage of KND y and Ag RP neurons that colocalized IR β, consistent with reduced insulin sensitivity. Administration of the anti‐androgen drug, Flutamide, during prenatal T treatment, prevented the reduction in IR β colocalization in Ag RP , but not in KND y 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 KND y and Ag RP neurons, may contribute to the PCOS ‐like phenotype of this animal model.