2017 journal article

AgRP to Kiss1 neuron signaling links nutritional state and fertility

Proceedings of the National Academy of Sciences of the United States of America, 114(9), 2413–2418.

By: S. Padilla*, J. Qiu*, C. Nestor*, C. Zhang*, A. Smith*, B. Whiddon*, O. Ronnekleiv*, M. Kelly*, R. Palmiter*

MeSH headings : Agouti-Related Protein / deficiency; Agouti-Related Protein / genetics; Animals; Circadian Clocks / drug effects; Circadian Clocks / physiology; Clozapine / analogs & derivatives; Clozapine / pharmacology; Estrous Cycle / drug effects; Estrous Cycle / physiology; Female; Fertility / drug effects; Fertility / genetics; Gene Expression Regulation; Gonadotropin-Releasing Hormone / genetics; Gonadotropin-Releasing Hormone / metabolism; Hypothalamus / drug effects; Hypothalamus / metabolism; Kisspeptins / genetics; Kisspeptins / metabolism; Leptin / genetics; Leptin / metabolism; Luteinizing Hormone / genetics; Luteinizing Hormone / metabolism; Male; Mice; Mice, Transgenic; Neurons / cytology; Neurons / drug effects; Neurons / metabolism; Optogenetics; Reproduction / drug effects; Reproduction / genetics; Signal Transduction; Starvation / genetics; Stereotaxic Techniques
Source: NC State University Libraries
Added: August 6, 2018

Significance Women suffering from malnutrition and athletes with low body fat become infertile as a result of low gonadotropin secretion. Gonadotropin release is determined by a neural endocrine circuit; however, the metabolic cues that are responsible for attenuating this axis during starvation remain unclear. Here, we find that starvation-activated agouti-related peptide (AgRP) neurons can inhibit the reproductive neuroendocrine circuit. Furthermore, artificial activation of genetically defined AgRP neurons is sufficient to delay estrous cycle length and parturition in female mice. This work demonstrates a mechanism by which AgRP neurons can relay metabolic information to the fertility axis during starvation.