Rapid increase in glycerol phosphate dehydrogenase mRNA in adult rat brain: a glucocorticoid-dependent stress response.
Twenty-five years ago, glycerol phosphate dehydrogenase (GPDH, EC 1.1.1.8) was described as a hormonally dependent enzyme in the brain, and since then has been characterized for its developmental regulation and as a marker for oligodendrocytes. These studies describe the cloning of GPDH mRNA from adult rat hippocampus and its characterization as an in vivo response in the brain to both glucocorticoid treatment and stress. A nearly full-length cDNA clone was obtained with sequence homology to the adult mouse GPDH gene. Three EcoRI fragments derived from this clone each hybridized to a major 2.9-kb transcript in poly(A)-containing RNA. GPDH mRNA increased up to 10-fold in a dose-dependent manner in response to acute corticosterone (CORT) treatment (8 h-3 days) of adrenalectomized (ADX) rats. Hybrid-selected GPDH mRNA encodes a 35-kD, pI 6.3 polypeptide that comigrated with our previously described CORT-responsive 35-kD in vitro translation product, with which it shares the same response characteristics. The basal (morning) AM prevalence of GPDH mRNA in the hippocampus is approximately 0.5 pg/micrograms total RNA. Shaking stress increased GPDH mRNA 4-fold; this increase was completely blocked by prior ADX. Hippocampal GPDH mRNA prevalence in ADX rats did not differ from AM intact rats, but increased to stress levels within 2 h of a CORT treatment that produced serum levels in the high physiological or stress range. GPDH expression increased throughout the brain of CORT-treated compared with ADX rats by in situ hybridization; the pattern of expression is similar to that of proteolipid protein mRNA and is consistent with a predominant expression in oligodendrocytes in white matter. Restraint and cold stress also increased GPDH mRNA in the brainstem. These results establish GPDH mRNA as a glucocorticoid-dependent stress response in adult rat hippocampus and indicate that glucocorticoid regulation of GPDH enzyme activity throughout the brain could result from changes in GPDH mRNA prevalence. In addition to its role in development, GPDH may participate in oligodendrocyte responses to stress in the adult brain.
Masters
J N
JN
Division of Neurogerontology, Andrus Gerontology Center, University of Southern California, Los Angeles 90089-0191.
Finch
C E
CE
Nichols
N R
NR
D000315:Adrenalectomy; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D003001:Cloning, Molecular; D003345:Corticosterone / Q000494:pharmacology; D015246:Deoxyribonuclease EcoRI; D005938:Glucocorticoids / Q000494:pharmacology*; D005993:Glycerolphosphate Dehydrogenase / Q000235:genetics*; D006624:Hippocampus / Q000201:enzymology; D017403:In Situ Hybridization; D007526:Isoelectric Point; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013312:Stress, Physiological / Q000201:enzymology*
D005938:Glucocorticoids; D012333:RNA, Messenger; D005993:Glycerolphosphate Dehydrogenase; D015246:Deoxyribonuclease EcoRI; D003345:Corticosterone