PACAP neurons in the ventral premammillary nucleus regulate reproductive function in the female mouse
Year: 2018
Type: article
Abstract: Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuromodulator implicated in anxiety, metabolism and reproductive behavior. PACAP global knockout mice have decreased fertility and PACAP modulates LH release. However, its source and role at the hypothalamic level remain unknown. We demonstrate that PACAP-expressing neurons of the ventral premamillary nucleus of the hypothalamus (PMV PACAP ) project to, and make direct contact with, kisspeptin neurons in the arcuate and AVPV/PeN nuclei and a subset of these neurons respond to PACAP exposure. Targeted deletion of PACAP from the PMV through stereotaxic virally mediated cre- injection or genetic cross to LepR-i-cre mice with PACAP fl/fl mice led to delayed puberty onset and impaired reproductive function in female, but not male, mice. We propose a new, sex-specific role for PACAP-expressing neurons in the PMV in the relay of nutritional state information to regulate GnRH release by modulating the activity of kisspeptin neurons, thereby regulating reproduction. Disclosure statement The authors have nothing to disclose.
Source: eLife
DOI: 10.7554/elife.35960
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: Harvard Medical School, National Institutes of Health, Health Research Council of New Zealand, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Boston Area Diabetes Endocrinology Research Center, The AgRP / POMC -> Paraventricular (PVH) -> Parabrachial (PBN) -> Limbic/Reward Satiety Circuit, Fostering Research Mentorship and Training During Psychiatry Residency, The Kiss1 system in the neuroendocrine control of reproduction, Reproductive Physiology of Gonadotropin Synthesis, G2513047960, Leptin, GABAergic Neurons and the Feedback / Feedforward Regulation of Energy Balance, G2661966628, A Neural Circuit of Energy Expenditure Preventing Obesity, Training Program in Cardiovascular Research, G3043361207, Boston Nutrition Obesity Research Center, G3961832639, G4474911060, Dissecting the Role of Tachykinins in the Generation of GnRH Pulses, G5520316217, Glutamatergic Neurons in the Arcuate Nucleus (ARC) and Regulation of Satiety, G656313053, AgRP neurons: circadian control and interactions with the HPA axis, G7106380571, Harvard Clinical and Translational Science Center, G8245670873, Harvard Clinical and Translational Science Center, G9000011862, G9000036325, G9000045640, G9000076910, G9000104193, G9000202663, Reproductive physiology of gonadotropin synthesis, Deciphering the functional role of MKRN3 in puberty and reproduction
OpenAlex ID: W2802483186