title: Suppression of hypothalamic pro-opiomelanocortin (POMC) gene expression by daily melatonin supplementation in aging rats.
abstract: 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 microg 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 microg 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 microg 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.
authors.affiliation: VA Puget Sound Health Care System Mental Illness Research, Education and Clinical Center (DDR), Seattle, Washington 98108, USA. drasmuss@washington.edu
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Rasmussen
authors.forename: Brett T
authors.initials: BT
authors.lastname: Marck
authors.forename: Brian M
authors.initials: BM
authors.lastname: Boldt
authors.forename: Steven M
authors.initials: SM
authors.lastname: Yellon
authors.forename: Alvin M
authors.initials: AM
authors.lastname: Matsumoto
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D001835:Body Weight; D005786:Gene Expression Regulation / Q000187:drug effects*; D017403:In Situ Hybridization; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; D008550:Melatonin