Age-related decrease in proopiomelanocortin gene expression in the arcuate nucleus of the male rat brain.
The decline in reproductive function with aging is due in part to decreased gonadotropin-releasing hormone (GnRH) secretion. beta-Endorphin (beta E), an endogenous opioid peptide derived from proopiomelanocortin (POMC), is thought to exert a tonic inhibitory effect upon hypothalamic GnRH secretion. We tested the hypothesis that the age-related decrease in GnRH secretion in male rats is due to increased beta E synthesis, by comparing POMC mRNA levels in the arcuate nucleus (ARC) of intact young, middle-aged and old male rats. In an initial study (Study 1), sixteen 20-microns coronal sections each from the ARC of 3- (n = 5) and 23-month-old (n = 4) male Fischer 344 rats were anatomically matched and analyzed. In a second study (Study 2), four anatomically matched sections of caudal arcuate nucleus from 3- (n = 4), 11- (n = 7) and 23-month-old (n = 5) male rats were compared. POMC mRNA levels were quantitated by in situ hybridization histochemistry, using a 35S-labeled oligodeoxynucleotide probe complementary to a portion of rat POMC cDNA and computerized image analysis. The number of grains per cell and cells per section were used as indices of cellular POMC mRNA content and the number of neurons expressing the POMC gene, respectively. Cellular POMC mRNA content was significantly lower in old compared to young animals (Study 1: 54 +/- 3 vs. 74 +/- 2 grains/cell, p less than 0.01; Study 2: 59 +/- 2 vs. 71 +/- 2 grains/cell, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Gruenewald
D A
DA
V.A. Medical Center, University of Washington School of Medicine, Seattle 98108.
Matsumoto
A M
AM
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D015870:Gene Expression / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006651:Histocytochemistry; D007031:Hypothalamus / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009693:Nucleic Acid Hybridization; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011916:Rats, Inbred F344; D013194:Staining and Labeling; D013739:Testosterone / Q000097:blood; D001615:beta-Endorphin / Q000502:physiology
D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D007986:Luteinizing Hormone