Science
Hormone Cell Atlas reframes endocrine system as distributed
Clinical takeaway: The atlas is a discovery and reference resource rather than a guide to practice, though it offers a framework for anticipating off-target effects of hormone-based therapies.
Hormones have long been taught as the products of dedicated glands, secreted into the blood to act on distant targets. That picture has been expanding for decades as tissues like fat and gut earned recognition as endocrine organs. A new resource asks how far that picture should extend, mapping where hormones and their receptors are made and sensed across the body at single-cell resolution.
Researchers analyzed 379 hormone and receptor genes across 14 million single cells and nuclei from 47 human tissues, drawn from more than 1,000 disease-free adult donors and 108 published studies. They then tied each cell type to hormones it can produce and respond to, assembling the results into the Hormone Cell Atlas.
Among the cell types catalogued, 74% were predicted to have hormone-secreting potential and 93% to respond to at least one hormone. Clustering cells by hormone-gene expression showed endocrine activity tracked cellular lineage more closely than tissue of origin, suggesting the capacity is a broad property of human cells rather than a specialty of a few glands. Classical hormones such as pituitary and gut peptides stayed tightly restricted to their expected cells, while production of others extended across many cell types.
The atlas also surfaced hormones in unexpected places. The clearest example is secretin, the gut peptide that in 1902 became the first molecule called a hormone. It turned up in plasmacytoid dendritic cells, rare immune cells central to antiviral defense. The team confirmed the signal spatially in tonsil tissue and at the protein level in blood; it found secretin rose in these cells during COVID-19 and influenza infection but not in non-infectious disease, hinting at a role in the immune response that will need direct testing.
A second example carries the most immediate relevance to prescribing. Receptors for the incretin hormones GLP-1 and GIP, the targets of widely used obesity and diabetes drugs, were mapped to cardiomyocytes and the pacemaker cells of the heart's sinoatrial and atrioventricular nodes. The authors note this raises the possibility that any cardiovascular benefits or risks of these drugs arise partly from direct action on the heart, not solely from weight loss or glycemic control.
The atlas reproduces well-established endocrine feedback circuits, such as the loops linking the pituitary to the thyroid and adrenal glands, from gene expression alone. That it rediscovers textbook biology unprompted is a check that the method works, lending weight to its novel predictions.
The same approach pinpoints the specific cells expressing genes behind rare monogenic endocrine disorders. The main value is as a discovery tool: a browsable framework for asking where a hormone or drug might act, and for flagging off-target sites worth investigating.
"By combining cellular resolution with a system-level view, the Hormone Cell Atlas exposes the breadth and complexity of the human endocrine system," the authors write. They frame it as a foundation for future mechanistic and physiological work.
Source: Fei L. Science. 2026 May 28. A Hormone Cell Atlas maps the human endocrine system at cellular resolution