Dysfunction in the Hypothalamo-Hypophyseal System under Chronic Stress and Fatigue

Chronic stress can cause a variety of symptoms such as severe fatigue, sleep disorder, and abnormal pain, although the underlying mechanisms have not been identified. Patients with chronic fatigue syndrome (CFS) experience severe fatigue that devastates the quality of their lives. However, the causes of this illness, as well as its diagnostic markers, remain unclear. An animal model is crucial for addressing the pathophysiology on both a molecular and cellular bases, then we have recently employed a continuous stress model in rats. Using this model, we could detect several changes in hypothalamo-hypophyseal systems. Some pituitary cells were affected functionally and morphologically by the continuous stress. For instance, somatotrophs showed atrophic morphology and functionally suppressed characteristics, whereas melanotrophs showed hyperactive and even degenerative morphology. A transcriptomic analysis demonstrated that several gene expressions were altered in the pituitary gland. Intriguingly, all of the changes were caused by the altered expression of molecules in the hypothalamus. These results suggest that chronic stress initially affects neurons in the brain and that these alterations cause disintegration in the endocrine center such as the pituitary gland, thereby further leading to disorders of various peripheral organs.