PACAP neurons in the ventral premammillary nucleus regulate reproductive function in the female mouse
- Beth Israel Deaconess Medical Center, United States
- Harvard Medical School, United States
- University of Otago, New Zealand
- Brigham and Women's Hospital, United States
- Tufts University School of Medicine, United States
Abstract
Pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) 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 (PMVPACAP) 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 Adcyap1fl/fl mice led to delayed puberty onset and impaired reproductive function in female, but not male, mice. We propose a new 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 in female mice.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
National Institutes of Health (R01 HD090151-A1)
- Victor M Navarro
National Institutes of Health (P30 DK057521)
- Bradford B Lowell
National Institutes of Health (R01 HD082314)
- Ursula B Kaiser
National Institutes of Health (R01 HD019938)
- Ursula B Kaiser
National Institutes of Health (R00 HD071970)
- Victor M Navarro
National Institutes of Health (5T32HL007374-36)
- Rachel A Ross
National Institutes of Health (R01 DK075632)
- Bradford B Lowell
National Institutes of Health (R01 DK089044)
- Bradford B Lowell
National Institutes of Health (R01 DK111401)
- Bradford B Lowell
National Institutes of Health (P30 DK046200)
- Bradford B Lowell
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal care and experimental procedures were approved by the National Institute of Health, Beth Israel Deaconess Medical Center and Brigham and Women's Hospital Institutional Animal Care and Use Committee . protocol #05165.
Copyright
© 2018, Ross et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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PACAP neurons in the ventral premammillary nucleus regulate reproductive function in the female mouse
eLife 7:e35960.
https://doi.org/10.7554/eLife.35960
