Sugihara H, Wakabayashi I, Minami S, Takahashi F, Shibasaki T, Ling N
Department of Medicine, Nippon Medical School, Tokyo, Japan.
Brain Res. 1988 Dec 13;475(1):128-33. doi: 10.1016/0006-8993(88)90205-3.
The effects of alpha-methyl-p-tyrosine (alpha-MT) and an antiserum specific to rat growth hormone-releasing factor (GRF) on growth hormone (GH) secretory profile during a 6-h continuous infusion of human GRF(1-44) NH2 were observed in unrestrained adult male Wistar rats. All rats were provided with two indwelling cannulae; one in the right atrium for undisturbed blood collection and the other in the inferior vena cava for 0.9% NaCl or GRF infusion. GRF was administered by an infusion pump at a dose of 50 ng/kg b.wt./min ma GH levels during baseline period were low with little fluctuation. GH secretion was augmented significantly during continuous GRF infusion in control rats but interpeak intervals remained unaltered. When an antiserum specific to rat GRF was administered, episodic GH secretion was abolished. In these rats, pulsatile GH secretion indistinguishable from that of control rats was observed in the continuous presence of human GRF. Although alpha-MT inhibited episodic GH secretion, alpha-MT-treated rats exhibited high-frequency, low-amplitude episodic GH secretion and elevated baseline levels during the stimulation. There were no differences in the amount of GH secreted during GRF infusion between rats that had received either alpha-MT or antiserum to rat GRF. Since GH secretion to GRF is determined largely by somatostatin, the results suggest that phasic release of somatostatin plays an important role in determining the rhythmicity of episodic GH secretion, and that it is modulated by alpha-MT but not by the immunoneutralization of GRF.
在未束缚的成年雄性Wistar大鼠中,观察了α-甲基-对-酪氨酸(α-MT)和大鼠生长激素释放因子(GRF)特异性抗血清对人GRF(1-44) NH₂连续输注6小时期间生长激素(GH)分泌模式的影响。所有大鼠均植入两根留置套管;一根置于右心房用于采集未受干扰的血液,另一根置于下腔静脉用于输注0.9%氯化钠或GRF。GRF由输液泵以50 ng/kg体重/分钟的剂量给药。基础期的GH水平较低且波动较小。在对照大鼠连续输注GRF期间,GH分泌显著增加,但峰间间隔保持不变。当给予大鼠GRF特异性抗血清时,GH的脉冲式分泌被消除。在这些大鼠中,在持续存在人GRF的情况下,观察到与对照大鼠难以区分的脉冲式GH分泌。尽管α-MT抑制了GH的脉冲式分泌,但α-MT处理的大鼠在刺激期间表现出高频、低幅度的脉冲式GH分泌以及升高的基础水平。接受α-MT或大鼠GRF抗血清的大鼠在GRF输注期间分泌的GH量没有差异。由于对GRF的GH分泌很大程度上由生长抑素决定,结果表明生长抑素的阶段性释放在决定脉冲式GH分泌的节律性方面起重要作用,并且它受α-MT调节,但不受GRF的免疫中和作用调节。