Cuttler L, Welsh J B, Szabo M
Endocrinology. 1986 Jul;119(1):152-8. doi: 10.1210/endo-119-1-152.
To test the hypothesis that relative resistance of the somatotroph to somatostatin (SRIF) contributes to elevated circulating levels of GH in the newborn rat, we examined the effects of SRIF (0.1, 0.33, and 1 nM) on basal, human pancreatic GH-releasing factor-40 (hpGRF-40; 1 nM)-stimulated, and (Bu)2cAMP (0.5 mM)-stimulated GH release from pituitary cells of 2-day-old, 15-day-old, and adult Sprague-Dawley rats in monolayer culture. The effect of SRIF on basal GH release varied markedly with age. SRIF, in the doses studied, did not inhibit basal GH release (nanograms of GH per 10(5) cells/3 h) from pituitary cultures of 2-day-old rats. In those of 15-day-old rats, only the two higher doses of SRIF (0.33 and 1 nM) suppressed GH release. By contrast, in pituitary cell cultures of adult male and female rats, all doses of SRIF significantly inhibited basal GH release (P less than 0.001). Similarly, the degree of SRIF suppression of both hpGRF-40- and (Bu)2cAMP-stimulated GH release differed among the age groups. In pituitary cultures of 2-day-old rats, SRIF did not significantly inhibit stimulated GH release. In 15-day-old rat pituitary cells, SRIF inhibited GH release, but did not eradicate the stimulatory effect of hpGRF-40 or (Bu)2cAMP. By contrast, in pituitary cell cultures of adult male and female rats, SRIF completely abolished the stimulatory effect of both hpGRF-40 and (Bu)2cAMP. When expressed as a percentage of the control (or stimulated) value, GH release at each SRIF dose varied markedly with age (P less than 0.001). Furthermore, a similar age-associated trend was evident when, in a separate series of experiments (n = 37), we examined the suppressive effect of a single concentration of SRIF (0.33 nM) on (Bu)2cAMP (0.5 mM)-stimulated GH release in cultured pituitary cells of rats ranging in age from -1 (day 20 of gestation) to 78 days. The degree of suppression increased progressively with advancing age; GH release decreased from 82 +/- 2% (+/- SE) of stimulated values in cultured cells of perinatal rats to 20 +/- 1% of stimulated values in cultured cells of 78-day-old rats. There was a significant negative correlation between age and SRIF-inhibited GH release (r = -0.89; P less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)
为验证生长激素分泌细胞对生长抑素(SRIF)的相对抵抗性导致新生大鼠循环中生长激素(GH)水平升高这一假说,我们检测了SRIF(0.1、0.33和1 nM)对2日龄、15日龄及成年Sprague-Dawley大鼠单层培养垂体细胞基础状态、人胰腺生长激素释放因子-40(hpGRF-40;1 nM)刺激状态及(Bu)2cAMP(0.5 mM)刺激状态下GH释放的影响。SRIF对基础GH释放的影响随年龄显著变化。在所研究的剂量下,SRIF并未抑制2日龄大鼠垂体培养物的基础GH释放(每10(5)个细胞/3小时的GH纳克数)。在15日龄大鼠中,只有两个较高剂量的SRIF(0.33和1 nM)抑制了GH释放。相比之下,在成年雄性和雌性大鼠的垂体细胞培养物中,所有剂量的SRIF均显著抑制基础GH释放(P<0.001)。同样,SRIF对hpGRF-40和(Bu)2cAMP刺激的GH释放的抑制程度在不同年龄组中也有所不同。在2日龄大鼠的垂体培养物中,SRIF并未显著抑制刺激后的GH释放。在15日龄大鼠的垂体细胞中,SRIF抑制了GH释放,但并未消除hpGRF-40或(Bu)2cAMP的刺激作用。相比之下,在成年雄性和雌性大鼠的垂体细胞培养物中,SRIF完全消除了hpGRF-40和(Bu)2cAMP的刺激作用。当以对照(或刺激)值的百分比表示时,每个SRIF剂量下的GH释放随年龄显著变化(P<0.001)。此外,在另一系列实验(n = 37)中,当我们检测单一浓度的SRIF(0.33 nM)对年龄从-1(妊娠第20天)至78天的大鼠培养垂体细胞中(Bu)2cAMP(0.5 mM)刺激的GH释放的抑制作用时,也出现了类似的年龄相关趋势。抑制程度随年龄增长而逐渐增加;GH释放从围产期大鼠培养细胞中刺激值的82±2%(±SE)降至78日龄大鼠培养细胞中刺激值的20±1%。年龄与SRIF抑制的GH释放之间存在显著负相关(r = -0.89;P<0.001)。(摘要截短于400字)