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Prenatal Testosterone Excess Decreases Neurokinin 3 Receptor Immunoreactivity within the Arcuate Nucleus KND y Cell Population
Author(s) -
Ahn T.,
Fergani C.,
Coolen L. M.,
Padmanabhan V.,
Lehman M. N.
Publication year - 2015
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12244
Subject(s) - neurokinin b , endocrinology , medicine , kisspeptin , arcuate nucleus , testosterone (patch) , population , hypothalamus , receptor , biology , gonadotropin releasing hormone , hormone , substance p , neuropeptide , luteinizing hormone , environmental health
Prenatal exposure of the female ovine foetus to excess testosterone leads to neuroendocrine disruptions in adulthood, as demonstrated by defects in responsiveness with respect to the ability of gonadal steroids to regulate gonadotrophin‐releasing hormone (Gn RH) secretion. In the ewe, neurones of the arcuate nucleus ( ARC ), which co‐expresses kisspeptin, neurokinin B ( NKB ) and dynorphin (termed KND y cells), play a key role in steroid feedback control of Gn RH and show altered peptide expression after prenatal testosterone treatment. KND y cells also co‐localise NKB receptors ( NK 3R), and it has been proposed that NKB may act as an autoregulatory transmitter in KND y cells where it participates in the mechanisms underlying steroid negative‐feedback. In addition, recent evidence suggests that NKB / NK 3R signalling may be involved in the positive‐feedback actions of oestradiol leading to the Gn RH /luteinising hormone ( LH) surge in the ewe. Thus, we hypothesise that decreased expression of NK 3R in KND y cells may be present in the brains of prenatal testosterone‐treated animals, potentially contributing to reproductive defects. Using single‐ and dual‐label immunohistochemistry we found NK 3R‐positive cells in diverse areas of the hypothalamus; however, after prenatal testosterone treatment, decreased numbers of NK 3R immunoreactive (‐ IR ) cells were seen only in the ARC . Moreover, dual‐label confocal analyses revealed a significant decrease in the percentage of KND y cells (using kisspeptin as a marker) that co‐localised NK 3R. To investigate how NKB ultimately affects Gn RH secretion in the ewe, we examined Gn RH neurones in the preoptic area ( POA ) and mediobasal hypothalamus ( MBH ) for the presence of NK 3R. Although, consistent with earlier findings, we found no instances of NK 3R co‐localisation in Gn RH neurones in either the POA or MBH ; in addition, > 70% Gn RH neurones in both areas were contacted by NK 3R‐ IR presynaptic terminals suggesting that, in addition to its role at KND y cell bodies, NKB may regulate Gn RH neurones by presynaptic actions. In summary, the finding of decreased NK 3R within KND y cells in prenatal testosterone‐treated sheep complements previous observations of decreased NKB and dynorphin in the same population, and may contribute to deficits in the feedback control of Gn RH / LH secretion in this animal model.