Hormones
Our gland-mass models of the human stress pathway (HPA - accompanied by longitudinal measurements of hair cortisol), thyroid axis, beta cells and ovaries explain phenomena on the timescale of weeks-months. These phenomena include addiction, depression, bipolar disorder mood episodes, prediabetes, subclinical thyroid diseases, ovarian dynamics and PCOS, and hormone seasonality. The growth and shrinkage of glands also provides systems level functions such as dynamic compensation (strict homeostasis of key variables and strict robustness of their dynamic response curves to a given stimulus) in the face of variation in physiological parameters such as insulin resistance, blood volume and metabolic state of the cells.
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A New Model For the Hpa Axis Explains Dysregulation of Stress Hormones on the Timescale of Weeks
The study developed a mathematical model showing that changes in the mass of HPA hormone-secreting glands, driven by stress hormones, explain the dysregulation of the HPA axis in stress-related disorders through a mechanism called dynamical compensation.
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Hormone seasonality in medical records suggests circannual endocrine circuits
The study found that human hormones exhibit clear seasonal patterns, with effector hormones peaking in winter-spring and their regulating pituitary hormones peaking months later in summer, suggesting a circannual clock mechanism driven by gland mass changes.
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An opponent process for alcohol addiction based on changes in endocrine gland mass
The study proposes that slow changes in the mass of HPA glands act as an opponent process for β-endorphin secretion in alcohol addiction, explaining hormone dynamics and suggesting gland mass changes as potential intervention targets.
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Dynamics of Thyroid Diseases and Thyroid-Axis Gland Masses
The study explains that delays in normalizing TSH levels after thyroid hormone treatment are due to a feedback mechanism where thyroid and pituitary gland growth, controlled by peripheral thyroid hormones and TSH, takes weeks to recover, suggesting new approaches for treating thyroid disorders.
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Major depressive disorder and bistability in an HPA-CNS toggle switch
The study proposes a mathematical model for MDD that explains the slow, weeks-long dynamics of the disorder through changes in HPA gland mass and mutual inhibition with the CNS, highlighting why prolonged stress can trigger persistent depressive episodes and why treatments take weeks to show effects.
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Rules for body fat interventions based on an operating point mechanism
The study introduces the operating point model, which explains how different fat reduction interventions affect food intake and fat levels based on leptin control, highlighting why some interventions have opposing or coherent effects and why some show overshoot in food intake.
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Timescales of Human Hair Cortisol Dynamics
The study measured cortisol levels over a year using hair samples from 55 healthy participants, finding non-seasonal fluctuations and slow frequencies that can be explained by a mathematical model of the HPA axis, highlighting the importance of understanding long-term cortisol dynamics for mood disorders.
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The study shows that drugs targeting the HPA axis often fail to lower long-term cortisol in mood disorders due to gland-mass compensation. It identifies CRH-neutralizing antibodies and CRH-synthesis inhibitors as potential targets to effectively lower cortisol, emphasizing the importance of understanding slow compensatory mechanisms in endocrine axes.
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Unifying regulatory motifs in endocrine circuits
The study identifies five classes of hormone circuits in human endocrine systems, each with unique regulatory logic for functions like homeostasis and response to stimuli. These circuits operate on two timescales: hormone secretion (minutes-hours) and gland mass changes (months), with detailed analysis of the pituitary circuit revealing tradeoffs in endocrine regulation.
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Endocrine gland size is proportional to its target tissue size
The study finds that the number of endocrine cells secreting a hormone is proportional to the number of target cells, with one endocrine cell serving about 2,000 target cells, suggesting an economic principle where glands operate near their maximal capacity.