Minami S, Kamegai J, Sugihara H, Hasegawa O, Wakabayashi I
Department of Medicine, Nippon Medical School, Tokyo, Japan.
Endocrinology. 1992 Jul;131(1):247-53. doi: 10.1210/endo.131.1.1612002.
The neuronal expression of the protooncogene c-fos could serve as a marker of neural activity. To identify the brain sites responding to GH, rat brains after systemic administration of recombinant human GH (rhGH) were processed for hybridization histochemistry for c-fos mRNA. Adult male Wistar rats were hypophysectomized 10 days before rhGH administration. After hypophysectomy, rats received sc cortisone acetate (0.5 mg/kg BW) and L-T4 (20 microgram/kg BW) daily. Four international units (1.33 mg) of rhGH were given iv through an indwelling right atrial cannula. Vehicle was administered to control animals. The rhGH treatment was accompanied by expression of the c-fos gene in the arcuate nucleus (ARC) of the hypothalamus. The accumulation of the c-fos mRNA was transient, reaching maximum values at 60 min and decreasing thereafter to reach control levels within 120 min after rhGH injection. Among control animals, c-fos gene expression was not detected in the ARC. The c-fos mRNA was also detected in the paraventricular nucleus after rhGH administration; however, it was comparable to that in control animals. When rhGH was administered twice at 40-min intervals, c-fos gene expression was induced in the periventricular nucleus (PeV) as well as the ARC 40 min after the second rhGH injection. Throughout the studies, c-fos mRNA was not detected other than in the ARC, paraventricular nucleus, and PeV in the hypothalamus. In the ARC, distribution of the cells expressing the c-fos gene appears to overlap at least in part with somatostatin (SS) mRNA-containing cells. In the PeV, it appeared to correlate generally with the distribution of SS mRNA-containing cells. The data suggest that GH feeds back on neurons of hypothalamic PeV and ARC expressing SS mRNA, and that c-fos expression is involved in the feedback mechanism.
原癌基因c-fos的神经元表达可作为神经活动的标志物。为了确定对生长激素（GH）产生反应的脑区，对经全身注射重组人生长激素（rhGH）后的大鼠脑进行c-fos mRNA的杂交组织化学处理。成年雄性Wistar大鼠在注射rhGH前10天进行垂体切除。垂体切除后，大鼠每天皮下注射醋酸可的松（0.5mg/kg体重）和L-T4（20μg/kg体重）。通过留置的右心房插管静脉注射4国际单位（1.33mg）的rhGH。给对照动物注射溶剂。rhGH处理伴随着下丘脑弓状核（ARC）中c-fos基因的表达。c-fos mRNA的积累是短暂的，在60分钟时达到最大值，此后下降，在rhGH注射后120分钟内降至对照水平。在对照动物中，未在ARC中检测到c-fos基因表达。rhGH给药后，室旁核中也检测到了c-fos mRNA；然而，其与对照动物中的水平相当。当以40分钟的间隔两次注射rhGH时，在第二次注射rhGH后40分钟，室周核（PeV）以及ARC中诱导了c-fos基因表达。在整个研究过程中，除了下丘脑的ARC、室旁核和PeV外，未检测到c-fos mRNA。在ARC中，表达c-fos基因的细胞分布似乎至少部分与含生长抑素（SS）mRNA的细胞重叠。在PeV中，它似乎与含SS mRNA的细胞分布总体相关。数据表明，GH对表达SS mRNA的下丘脑PeV和ARC神经元产生反馈作用，并且c-fos表达参与了反馈机制。
