title: Chronic stress elicits prolonged activation of alpha-MSH secretion and subsequent degeneration of melanotroph.
abstract: Prolonged stress affects homeostasis in various organs and induces stress-associated disorders. We examined the cellular changes of pituitary gland under the continuous stress condition using a rat model in which rats were kept in a cage filled with water to a height of 1.5 cm for up to 5 days. Among the pituitary hormone mRNAs, proopiomelanocortin mRNA was up-regulated specifically in the intermediate lobe (IL) of this rat model. Additionally, the peripheral blood levels of alpha-melanocyte stimulating hormone (alpha-MSH), a major product of proopiomelanocortin in IL were increased. The alpha-MSH secreting cells, melanotrophs, showed a markedly developed endoplasmic reticulum and Golgi apparatus in the early phase of the experiment. Subsequent continuous stress caused remarkable dilation of the endoplasmic reticulum, disruption of the Golgi structure, and the degeneration of some melanotrophs. In addition the dopaminergic nerve fibers from hypothalamus were markedly decreased in IL. A dopamine antagonist elicited the similar morphologic changes of melanotroph in normal rat. These findings suggest that prolonged stress suppressed hypothalamus-derived dopamine release in IL, which elicited over-secretion of alpha-MSH from the melanotrophs. The present study also suggests that prolonged hyperactivation of endocrine cells could lead to disorder of secretion mechanisms and eventual degeneration.
authors.affiliation: Department of Anatomy & Neurobiology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Tokiko
authors.initials: T
authors.lastname: Ogawa
authors.forename: Nobue
authors.initials: N
authors.lastname: Shishioh-Ikejima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konishi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Makino
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Sei
authors.forename: Sumiko
authors.initials: S
authors.lastname: Kiryu-Seo
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyama
mesh_terms: D000818:Animals; D003214:Conditioning, Classical; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000009:adverse effects; D004721:Endoplasmic Reticulum / Q000473:pathology; D006056:Golgi Apparatus / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D052717:Melanotrophs / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000209:etiology*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D000521:alpha-MSH / Q000097:blood*
chemical_list: D015259:Dopamine Agents; D012333:RNA, Messenger; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D004298:Dopamine