GH
secretagogue (GHS)/
ghrelin stimulates GH secretion by binding mainly to its receptor (GHS-R) on GHRH neurons in the arcuate nucleus (
Arc) of the hypothalamus. GHRH,
somatostatin, and
neuropeptide Y (NPY) in the hypothalamus are involved in the regulatory mechanism of GH secretion. We previously created transgenic (Tg) rats whose GHS-R expression is reduced in the
Arc, showing lower
body weight and shorter nose-tail length. GH secretion is decreased in female Tg rats. To clarify how GHS-R affects GHRH expression in the
Arc, we compared the numbers of GHS-R-positive, GHRH, and NPY neurons between Tg and wild-type rats. Immunohistochemical analysis showed that the numbers of GHS-R-positive neurons, GHRH neurons, and GHS-R-positive GHRH neurons were reduced in Tg rats, whereas the numbers of NPY neurons and GHS-R-positive NPY neurons did not differ between the two groups. The numbers of Fos-positive neurons and Fos-positive GHRH neurons in response to
KP-102 were decreased in Tg rats. Competitive RT-PCR analysis of GHRH
mRNA expression in the cultured hypothalamic neurons showed that
KP-102 increased NPY
mRNA expression level and that NPY decreased GHRH
mRNA expression level.
KP-102 increased GHRH
mRNA expression level in the presence of anti-NPY
IgG. GH increased
somatostatin mRNA expression. Furthermore, GH and
somatostatin decreased GHRH
mRNA expression, whereas
KP-102 showed no significant effect on
somatostatin mRNA expression. These results suggest that GHS-R is involved in the up-regulation of GHRH and NPY expression and that NPY,
somatostatin, and GH suppress GHRH expression. It is also suggested that the reduction of GHRH neurons of Tg rats is induced by a decrease in GHS-R expression.