Endocrine Abstracts

JOINT46

Background: Despite the fundamental role of the endocrine system in human physiology, basic questions such as the total number of human hormones and their cumulative abundance have remained unanswered. While specific hormone circuits are well-studied, the relative abundance patterns across the entire human endocrinome remain undefined, limiting our understanding of system-wide endocrine regulation.

Methods and Findings: We conducted an integrative analysis of the human endocrinome by leveraging clinically validated reference ranges across major endocrine subsystems. We compiled data for the routinely assayed hormones spanning all endocrine glands and hormone-secreting tissues, validated our findings using published datasets, and developed strict inclusion criteria to systematically evaluate 7, 996 candidate molecules from published databases. This rigorous curation yielded a comprehensive list of 187 bona fide human hormones. Our analysis revealed that the total mass of circulating hormones in healthy young adults is approximately 40 mg (39.5±1.5mg for men, 41.5±1.5mg for women), with an estimated uncertainty under 5%. Two hormones, Adiponectin and DHEA-S are dominant, constituting over 90% of both total hormone mass and copy number. We identified marked sexual dimorphism, with females having approximately half the number of circulating hormone molecules compared to males in terms of absolute number (≈14 μmol vs ≈25 μmol). Analysis of abundance patterns revealed previously unrecognized relationships between hormone type, functionality, and abundance. These include the unexpected striking predominance of DHEA-S, usually referred to as merely another hormone precursor reservoir, and systematic deviations from established signal propagation patterns in hypothalamic-pituitary axes that suggest previously overlooked regulatory mechanisms. The main limitation of our study is the paucity of large unbiased datasets of hormone levels in healthy adults, as most hormones are not part of routine screening tests, creating inherent selection bias in existing clinical data.

Conclusions: This first comprehensive quantification of the human endocrinome establishes fundamental parameters of hormone abundance and distribution. Our systematic analysis reveals unexpected patterns in sexual dimorphism, hormone abundance hierarchies, and signal propagation schemes that challenge current paradigms of endocrine regulation. These findings provide an essential framework for developing targeted endocrine profiling approaches and understanding system-wide hormone dysregulation in pathological states.