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Suppression of hypothalamic pro‐opiomelanocortin (POMC) gene expression by daily melatonin supplementation in aging rats
Author(s) -
Rasmussen Dennis D.,
Marck Brett T.,
Boldt Brian M.,
Yellon Steven M.,
Matsumoto Alvin M.
Publication year - 2003
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1034/j.1600-079x.2003.00019.x
Subject(s) - melatonin , endocrinology , medicine , circadian rhythm , period (music) , hypothalamus , proopiomelanocortin , biology , physics , acoustics
Both plasma melatonin levels and hypothalamic arcuate nucleus pro‐opiomelanocortin (POMC) (biosynthetic precursor to the endogenous opioid ß‐endorphin and other opiomelanocortins) mRNA content decrease with aging. To test whether the decline in melatonin is responsible for the decline in POMC mRNA, we investigated the effects of daily melatonin treatment on hypothalamic POMC mRNA content in middle‐aged and older Sprague–Dawley rats. Daily nocturnal melatonin treatment (50 μg kg bw −1 night −1 , in the night‐time drinking water) for 7 months, starting at 13 months of age, did not significantly alter female arcuate nucleus POMC mRNA content determined at the end of the light period (i.e., before nightly melatonin administration), but suppressed (24%, P < 0.05) POMC mRNA content at the end of the dark period (i.e., following melatonin administration). Likewise, nocturnal administration of 50 or 500 μg melatonin kg bw −1 night −1 to male rats for 7 months suppressed (31 or 28%, respectively; P < 0.05) POMC mRNA content at the middle of the dark period at 20 months of age. Finally, 10 wk administration of 30 μg melatonin kg bw −1 day −1 suppressed (31%, P < 0.01) POMC mRNA content in middle‐aged male rats killed at the end of the dark period. Melatonin treatments did not significantly alter estradiol or testosterone levels. Thus, moderate‐dosage nocturnal melatonin supplementation suppressed nocturnal hypothalamic POMC gene expression in both middle‐aged males and females, suggesting that melatonin supplementation during aging decreases, rather than increases, forebrain opiomelanocortinergic activity. These POMC responses were apparently not dependent on gonadal steroid responses and did not become refractory to melatonin treatment maintained until old age.