Unifying design principles of endocrine gland mass and its regulatory circuits

Hormones are regulatory molecules that impact physiological functions. Much is known about individual hormones, but general rules that connect the regulatory logic of different hormone systems are limited. In this study, we analyzed a range of human hormone systems using a mathematical approach to integrate knowledge on endocrine cells, target tissues and regulation, to uncover unifying principles and regulatory circuits. We find that the number of cells in an endocrine gland is proportional to the number of cells in its target tissues, as one single endocrine cell serves approximately 2000 target cells. We identified five classes of regulatory circuits, each has specific regulatory functions such as homeostasis or allostasis. The most complex class includes an intermediate gland, the pituitary, which can otherwise be considered redundant and exposes to fragilities. We suggest a tradeoff: with the price of fragilities comes advantages -amplification, buffering of hypersecreting tumors, and faster response times. By elucidating these unifying principles and circuits, this study deepens our understanding of the control of endocrine processes and builds the foundation for systems endocrinology.