Unifying regulatory motifs in endocrine circuits

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.