Kamegai J, Hasegawa O, Minami S, Sugihara H, Wakabayashi I
Department of Medicine, Nippon Medical School, Tokyo, Japan.
Brain Res Mol Brain Res. 1996 Jul;39(1-2):153-9. doi: 10.1016/0169-328x(96)00020-4.
Growth hormone-releasing hexapeptide (GHRP) stimulates GH secretion by acting on both the pituitary and the hypothalamus through a poorly understood mechanism. To reveal the hypothalamic action of GHRP, rat brains were processed for in situ hybridization for c-fos mRNA as a marker of neuronal activity after systemic administration of a newly developed GHRP, KP-102. Hypophysectomized adult male Wistar rats were administered KP-102 through an indwelling right atrial cannula. KP-102 treatment was accompanied by transient expression of the c-fos gene selectively in the ventromedial and ventrolateral regions of the arcuate nucleus (ARC). The distribution of c-fos gene-expressing cells overlapped that of GRF mRNA-containing neurons in the ventrolateral region on adjacent sections, whereas few c-fos mRNA signals were detected in the dorsomedial region where somatostatin mRNA signals were localized. To confirm this observations, hypothalamic sections were subjected to double-label in situ hybridization. Twenty-three percent of c-fos mRNA-containing cells were GRF neurons, comprising 20% of the GRF neurons in the ARC. The remaining c-fos mRNA containing cells were unidentified. KP-102 thus appears to act on a subpopulation of GRF neurons and unidentified cells in the ARC to stimulate GH secretion.
生长激素释放六肽（GHRP）通过一种尚不清楚的机制作用于垂体和下丘脑，从而刺激生长激素（GH）的分泌。为了揭示GHRP在下丘脑的作用机制，在给成年雄性Wistar大鼠全身注射新开发的GHRP（KP - 102）后，将大鼠脑进行处理，以c - fos mRNA原位杂交作为神经元活动的标记。对垂体切除的成年雄性Wistar大鼠通过右心房留置插管给予KP - 102。给予KP - 102后，c - fos基因在弓状核（ARC）的腹内侧和腹外侧区域选择性地短暂表达。在相邻切片上，表达c - fos基因的细胞分布与腹外侧区域含生长激素释放因子（GRF）mRNA的神经元分布重叠，而在生长抑素mRNA信号所在的背内侧区域几乎检测不到c - fos mRNA信号。为了证实这一观察结果，对下丘脑切片进行了双重标记原位杂交。含c - fos mRNA的细胞中有23%是GRF神经元，占ARC中GRF神经元的20%。其余含c - fos mRNA的细胞身份不明。因此，KP - 102似乎作用于ARC中GRF神经元的一个亚群和身份不明的细胞，以刺激GH分泌。
