Unifying regulatory motifs in endocrine circuits
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Hormone systems, which control diverse physiological functions, have been extensively studied, yet consistent rules underlying these systems remain elusive. Here we identify unifying design principles in human endocrine systems. Available data was found for 43 of 63 systems, and all 43 fall into five classes of circuits. Each class uses distinct regulation circuitry to perform specific dynamical functions: homeostasis, acute input-output response, or adjustable set points. The circuits involve interactions across multiple timescales — minutes to hours for hormone secretion, ultradian and diurnal rhythms, and weeks for changes in endocrine gland mass. The weeks-timescale for gland mass occurs in several circuit classes, including the most complex, which features an intermediate gland, the pituitary. We analyze this circuit in detail and identify tradeoffs between endocrine amplification, buffering of hypersecreting tumors, and response times. These unifying principles reveal how circuit structure maps to function and contribute to the emerging field of systems endocrinology.
Date Issued
2025-12-10
Date Acceptance
2025-10-27
Citation
Nature Communications, 2025, 16
ISSN
2041-1723
Publisher
Nature Portfolio
Journal / Book Title
Nature Communications
Volume
16
Copyright Statement
© The Author(s) 2025 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41271754
PII: 10.1038/s41467-025-65924-4
Subjects
ADENOMAS
CORTISOL
EXPRESSION
GLUCOSE
INSULIN
Multidisciplinary Sciences
NETWORK
PHYSIOLOGY
PLASMA
Science & Technology
Science & Technology - Other Topics
SECRETION
STIMULATING-HORMONE RECEPTOR
Publication Status
Published
Coverage Spatial
England
Article Number
11017
Date Publish Online
2025-11-21