Prolactin receptor-expressing neurons in the hypothalamus regulate energy metabolism, bone calcium mobilization, and pain thresholds in mice during lactation, according to a study published in Nature Communications.
Researchers at the Johns Hopkins University School of Medicine examined how the brain governs maternal physiological adaptations. During lactation, female mammals experience significant bone loss alongside shifting metabolic requirements. The study established that prolactin stimulates tyrosine hydroxylase expression inside prolactin receptor-positive dopaminergic neurons located in the arcuate nucleus of the hypothalamus.
Lactating mice exhibited elevated neuropeptide Y expression, altering both energy demand and nociceptive thresholds. When the team knocked down either prolactin receptors or neuropeptide Y inside the arcuate nucleus, the mice showed significant reductions in food demand as well as lower nociceptive thresholds.
The hormone prolactin also drives skeletal regulation through a separate hypothalamic pathway. Prolactin induces tyrosine hydroxylase expression within the hypothalamic paraventricular nucleus, driving sympathetic outflow that mobilizes calcium from bone tissue. In addition, the researchers identified communication network factor 3, a brain-derived osteoanabolic hormone, downstream of prolactin receptor signaling in dopaminergic neurons.
Xu Cao led the study alongside co-authors Ningrong Chen, Shreya Kumar, Kalp Patel, Shangqing Li, Mei Wan, and Janet Crane at Johns Hopkins University School of Medicine. The National Institutes of Health funded the research under grants P01AG066603, R01AG076783, and R01AG068997, with animal models provided by Dr. Ron Banerjee at Johns Hopkins Bayview Medical Center.
