慢性過労による下垂体細胞の崩壊

抄録

Accumulated fatigue disrupts homeostasis in various organs, which sometimes leads to chronic fatigue and work-overload induced death. We examined the cellular changes that occur with the accumulation of fatigue in a rat fatigue model in which locomotor activity and a partial sleep disturbance are continuously induced. Prolonged fatigue stress induced a marked development of the rough endoplasmic reticulum (rER), enlargement of Golgi apparatus in the cells of the intermediate lobe of the pituitary gland (IL), and elevation of alpha-melanocyte stimulating hormone (a-MSH) in the peripheral blood. Further continuous stress caused dilation of the ER. The cells became full of dilated ER and began to degenerate. The prolonged fatigue stress markedly decreased tyrosine hydroxylase (TH)-positive nerve fibers in the IL. Injection of the dopamine antagonist to non-fatigued rats induced the same morphological changes of the ER and Golgi structures. Conversely, injection of a dopamine agonist to fatigued rats inhibited these changes. These findings suggest that prolonged fatigue stress suppressed dopamine release in the IL, causing oversecretion of IL hormone from the melanotrophs and leading to melanotroph dysfunction and subsequent cell death. This characteristic response observed in melanotrophs in chronic stress provides a possible marker for diagnosis and a potential therapeutic target for chronic fatigue. [J Physiol Sci. 2008;58 Suppl:S18]