Poster Presentation 4th Metabolic Diseases; Breakthrough Discoveries in Diabetes & Obesity Meeting 2024

Arcuate nucleus POMC neurons express receptors for the anterior pituitary hormone prolactin (#160)

Chenyun Fang 1 , Hollian R Phillipps 1 , Mohammed Z Rizwan 1 , Dave R Grattan 1
  1. Department of Anatomy and Centre for Neuroendocrinology, University of Otago, Dunedin, Otago, New Zealand

Pro-opiomelanocortin (POMC) neurons residing in the arcuate nucleus (ARC) of the hypothalamus are critical regulators of appetite and glucose homeostasis [1]. These neurons exhibit heterogeneity in receptor expression, including leptin and insulin receptors involved in glucose metabolism [2, 3]. Our analysis of single-cell RNA sequencing data [4] reveals that over half of POMC neurons express the prolactin receptor (PRLR), and if we specifically look at the subpopulation of POMC neurons that express the leptin receptor, over 95% of these POMC neurons co-express PRLR. This discovery suggests that elevated prolactin has the potential to influence body weight and/or glucose homeostasis via leptin-sensitive POMC neurons in the ARC region. To explore this further, we investigated whether mouse arcuate POMC neurons are prolactin-responsive. Using adult diestrous female PRLR-Cre td-Tomato reporter mice, where Cre-recombinase is co-expressed with the PRLR-encoding gene and visualized by td-Tomato expression, we identified approximately 60% of POMC neurons co-expressing endogenous td-Tomato-labeled PRLR throughout the arcuate region, with no significant difference in levels of colocalization between the caudal and rostral ARC. Our findings underscore a significant population of PRLR-expressing POMC neurons in the ARC region, suggesting a mechanism by which prolactin signaling might influence glucose metabolism and body weight homeostasis. Given that hyperprolactinemia is associated with increased food intake [5] and insulin resistance [6], prolactin signaling likely plays a role in metabolic regulation that could be particularly important in promoting adaptive changes in food intake and glucose homeostasis during times when prolactin levels are elevated, such as pregnancy and lactation. Our data suggest that these metabolic actions of prolactin may be mediated through the regulation of POMC neurons.

 

 

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