Hypothalamic somatostatin and growth hormone-releasing hormone mRNA expression depend upon GABA(A) receptor expression in the developing mouse.
Gonadal steroids exert an important regulatory influence upon the biosynthetic and secretory activity of the somatostatin and growth hormone-releasing hormone (GHRH) neurons controlling the release of growth hormone. It is hypothesized that some of these effects occur in an indirect transsynaptic manner through the steroid regulation of GAGAergic inputs to these cells. Using GABA(A) receptor gamma(2) subunit knockout mice (gamma(2)(-/-)), which exhibit marked deficiencies in GABA(A) receptor functioning, we have examined here whether signaling through the GABA(A) receptor has any role in maintaining normal levels of somatostatin and GHRH mRNA expression in vivo. In situ hybridization experiments using (35)S-labeled oligonucleotide probes revealed that cellular levels of somatostatin mRNA in the periventricular nucleus were significantly (p < 0.01) reduced by 16% in newborn gamma(2)(-/-) mice compared with wild-type litter mates (gamma(2)(+/+)). Somatostatin mRNA expression in the striatum was not changed. Cellular levels of GHRH mRNA expression in the arcuate nucleus were significantly (p < 0.05) reduced by 30% in gamma(2)(-/-) compared with gamma(2)(+/+) mice. These results demonstrate that deletion of the gamma(2) subunit of the GABA(A) receptor reduces somatostatin and GHRH mRNA expression within the hypothalamopituitary axis and indicate that GABA exerts a tonic stimulatory influence upon both somatostatin and GHRH biosynthesis in vivo in the neonatal mouse.
Pannell
Catherine
C
Laboratory of Neuroendocrinology, The Babraham Institute, Babraham, Cambridge, UK.
Simonian
Sharon X
SX
Gillies
Glenda E
GE
Luscher
Bernhard
B
Herbison
Allan E
AE
D000818:Animals; D000831:Animals, Newborn; D001111:Arcuate Nucleus of Hypothalamus / Q000254:growth & development / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010286:Paraventricular Hypothalamic Nucleus / Q000254:growth & development* / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D011963:Receptors, GABA-A / Q000235:genetics*; D013004:Somatostatin / Q000235:genetics*
D012333:RNA, Messenger; D011963:Receptors, GABA-A; D013004:Somatostatin; D013007:Growth Hormone-Releasing Hormone