Olchovsky D, Bruno J F, Berelowitz M
Department of Medicine, State University of New York at Stony Brook 11794, USA.
J Endocrinol. 1996 Feb;148(2):189-92. doi: 10.1677/joe.0.1480189.
Growth hormone-releasing factor (GRF) mRNA expression in male rats occurs predominantly in the hypothalamus (mainly in the arcuate nucleus), and among extraneural sites primarily in the testis. Hypothalamic GRF is the physiological tropic stimulus to growth hormone secretion. However, the role of GRF in the testis is unknown. We have shown previously that hypothalamic GRF mRNA expression is significantly reduced in streptozotocin (STZ)-diabetic rats. This reduction is confined to the arcuate nucleus and probably accounts for the suppression of growth hormone pulsatility. The present studies were performed to evaluate GRF expression in the testis of streptozotocin (STZ)-diabetic rats. Diabetes was induced by injection of STZ (100 mg/kg i.p.). Seventeen to twenty days later diabetic rats were hyperglycemic compared with vehicle-injected controls and demonstrated growth failure. Insulin treatment reduced the glycemia and increased body weight towards normal. Total RNA was extracted from the hypothalamus and testis, and GRF mRNA levels estimated by solution hybridization/nuclease protection assay. Levels of hypothalamic somatostatin mRNA were measured to serve as control values. GRF mRNA was significantly (P < 0.001) decreased in the hypothalamus of STZ-diabetic rats (0.2 +/- 0.07 mean relative densitometric units, n = 8) compared with controls (1.0 +/- 0.19, n = 8) with no change in somatostatin mRNA expression. In contrast, testicular GRF mRNA was increased 70% (P < 0.05) in STZ-diabetic rats. Insulin treatment resulted in normalization of hypothalamic GRF mRNA levels (1.1 +/- 0.17, n = 5) with no effect on testicular GRF mRNA expression. In conclusion GRF gene expression is discordantly regulated in tissues of male STZ-diabetic rats. While reduced GRF expression may account for the low growth hormone state in this model, increased testicular GRF mRNA (with the previously reported reduction of insulin-like growth factor-I mRNA) resembles the response seen in growth hormone-sensitive tissue (especially the hypothalamus) to this growth hormone-deficient state.
生长激素释放因子（GRF）mRNA在雄性大鼠中的表达主要发生在下丘脑（主要在弓状核），在神经外部位主要在睾丸。下丘脑GRF是生长激素分泌的生理性促生长刺激物。然而，GRF在睾丸中的作用尚不清楚。我们之前已经表明，链脲佐菌素（STZ）诱导的糖尿病大鼠下丘脑GRF mRNA表达显著降低。这种降低局限于弓状核，可能是生长激素脉冲分泌受抑制的原因。本研究旨在评估链脲佐菌素（STZ）诱导的糖尿病大鼠睾丸中GRF的表达。通过腹腔注射STZ（100mg/kg）诱导糖尿病。17至20天后，与注射赋形剂的对照组相比，糖尿病大鼠出现高血糖并表现出生长发育迟缓。胰岛素治疗可降低血糖并使体重增加至接近正常水平。从下丘脑和睾丸中提取总RNA，并通过溶液杂交/核酸酶保护试验估计GRF mRNA水平。测量下丘脑生长抑素mRNA水平作为对照值。与对照组（1.0±0.19，n = 8）相比，STZ诱导的糖尿病大鼠下丘脑GRF mRNA显著降低（P < 0.001）（平均相对光密度单位为0.2±0.07，n = 8），生长抑素mRNA表达无变化。相反，STZ诱导的糖尿病大鼠睾丸GRF mRNA增加70%（P < 0.05）。胰岛素治疗使下丘脑GRF mRNA水平恢复正常（1.1±0.17，n = 5），对睾丸GRF mRNA表达无影响。总之，雄性STZ诱导的糖尿病大鼠组织中GRF基因表达受到不一致的调节。虽然GRF表达降低可能是该模型中生长激素水平低的原因，但睾丸GRF mRNA增加（与先前报道的胰岛素样生长因子-I mRNA降低）类似于生长激素敏感组织（尤其是下丘脑）对这种生长激素缺乏状态的反应。
