Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and N-methyl-D-aspartate receptor subunits gene transcripts in male rats.
Studies were conducted to evaluate the effects of s.c. injected recombinant human growth hormone (GH) on the expression of the gene transcript of N-methyl-D-aspartate receptor subunits type 1 (NR1), type 2A (NR2A), and type 2B (NR2B) in the male rat hippocampus. The GH-induced effects on the expression of hippocampal gene transcripts of GH receptor (GHR) and GH-binding protein were also examined. Male Sprague-Dawley rats, kept in four groups of two different ages, was treated with the hormone or saline during 10 days before decapitation and tissue dissection. Brain tissues collected were analyzed for mRNA content by using the Northern blot technique. The results indicated that in adult young rats (11 weeks of age) the hormone elicited a decrease in the mRNA expression of NR1 but an increase in that of the NR2B subunit. In elderly adult rats (57-67 weeks of age) GH induced an increase in the expression of the hippocampal message for NR1 and NR2A. Meanwhile, the hormone induced a significant up-regulation of the GHR transcript in hippocampus of adult young rats but not in elderly adult rats. It was further found that a significant positive correlation exists between the level of GHR mRNA and the expression of the NR2B subunit transcript in adult young rats. The GH-induced increase in the expression of hippocampal mRNA for the NR2B subunit is compatible with a previously observed memory promoting effect seen for the hormone, because overexpression of this N-methyl-D-aspartate receptor subunit is shown to enhance cognitive capabilities.
Le Grevès
Madeleine
M
Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden.
Steensland
Pia
P
Le Grevès
Pierre
P
Nyberg
Fred
F
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D011986:Receptors, Somatotropin / Q000235:genetics*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism
D002352:Carrier Proteins; C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D019382:Human Growth Hormone; C051815:somatotropin-binding protein