慢性氟中毒大鼠垂体生长激素细胞及下丘脑生长抑素神经元…

本实验对慢性氟中毒大鼠垂体生长激素（ＧＨ）细胞及下丘脑生长抑素（ＳＳ）神经元分析了免疫细胞化学染色，并用图像分析仪对ＧＨ及ＳＳ进行了半定量分析，结果表明：同对照组相比，氟中毒垂体ＧＨ细胞中的阳性反应颗粒细小并弥散地分布，半定量分析表明其ＧＨ含量明显低于对照组，未见下丘脑ＳＳ神经元及其ＳＳ含量有明显改变，本研究结果提示高氟可直接作用于垂体ＧＨ细胞影响其合成分泌功能。     

实验性慢性氟中毒大鼠垂体生长激素细胞的超微结构及酶细胞化学研究

本实验以饮用含100mg/L高氟水的方法复制了雄性大鼠实验性慢性氟中毒模型。用透射电镜观察了高氟对大鼠垂体生长激素(GH)细胞及其硫胺素焦磷酸酶(TPPase)活性的影响。结果表明:氟中毒大鼠垂体中大多数GH细胞的细胞器不如对照组发达;线粒体有破坏,基质密度增高,出现空泡或嵴减少;溶酶体增多,分泌颗粒数量增多但较小,说明GH细胞处于机能不活跃状态。电镜酶细胞化学研究结果显示氟中毒大鼠垂体GH细胞的TPPase活性受到抑制。结果提示高氟可能抑制垂体GH细胞的TPPase活性并影响其超微结构。     

吡啶斯的明对生长激素释放激素诱导正常人生长激素分泌的影响

胆碱能神经对控制垂体前叶生长激素(GH)分泌起着重要的作用,乙酰胆碱可能通过抑制下丘脑生长抑素(SS)的释放来调节GH的分泌。正常人不同个体间GH对生长激素释放激素(GHRH)的反应性有明显差异,这种差异性与个体间SS能神经张力不同有关。最近研究发现,乙酰胆碱脂酶抑制剂吡啶斯的明(PD)可抑制下丘脑SS释放,从而兴奋基础GH分泌及增加GH对GHRH的反应性。本文对正常人服用PD对GHRH诱导GH分泌的影响进行了研究。     

低碘大鼠垂体前叶细胞免疫组化观察

用免疫组织化染色PAP法,对低碘大鼠垂体前叶道TSH,GH,ACTH分泌激素细胞进行了观察及立体定量分析,结果显示TSH细胞数量增加,个别细胞体积增大,细胞变性明显,GH细胞数量减少,细胞谱性,ACTH细胞定量分析结果与对照组相比差异无显性。     

神经内分泌学与临床的联系——美国弗吉尼亚大学M.O.Thorner教授在京讲学报道

垂体前叶生长激素(GH)的分泌是接受下丘脑生长激素释放因子(GRF)和生长激素抑制因子(SS)的双重调节。GH通过促进体内多种周围组织生成生长介质C(IGF-Ⅰ),对代谢起着重要的调节作用。IGF-Ⅰ能反馈作用于垂体及下丘脑,通过促进SS的分泌,或直接作用于垂体,而抑制GH的分泌。     

慢性氟中毒大鼠中缝大核硫胺素焦磷酸酶细胞化学研究

目的探讨慢性氟中毒对大鼠中缝大核酶活性的影响。方法饮用高氟水(100mg／L)复制雄性大鼠慢性氟中毒模型。对中缝大核神经元硫胺素焦磷酸酶(TPPase)进行定性、定量分析。结果氟中毒大鼠中缝大核神经元内TPPase染色浅于对照组，定量分析TPPase活性下降。电镜观察氟中毒大鼠神经元内TPPase颗粒减少，同时出现超微结构改变。结论高氟可抑制TPPase酶的活性，对中枢神经系统有直接损害作用。     

慢性氟中毒授乳大鼠垂体催乳素细胞的超微结构研究

在透射电镜下观察了慢性氟中毒授乳大鼠垂体前叶催乳素细胞的超微结构变化。按其改变程度可分为三种类型:其一,大多数催乳素(PRL)细胞的结构基本正带,只核的异染色质增多,大的成熟颗粒明显多于对照组;其二,有些 PRL 细胞内线粒体增多并明显肿胀,内嵴减少或破坏,高尔基复合体的大泡增多,胞质中有大脂滴沉积;其三,有少数 PRL 细胞退化变性。同时测定血清 PRL 水平降低,垂体 PRL 含量及浓度升高。以上结果提示:慢性氟中毒可能使催乳素的释放受阻,并且氟对 PRL 细胞可能有直接的毒性作用。     

生长激素释放因子及其临床应用

1962年Frantz等即发现猪的下丘脑含有刺激生长激素(GH)分泌的物质存在,1964年Deuben等用纯化的或部份纯化的下丘脑浸出液加入鼠垂体培养液中发现GH含量明显增加。1971年Schally等从猪下丘脑浸出液及垂体门脉血中分离出一种10肽,用生物鉴定法证实它可刺激GH分泌。1982年以来Guillemin,Rivier及Thorner等先后报告胰岛细胞肿瘤及类癌患者有典型肢端肥大症临床表现伴血中GH明显升高而     

生长激素与糖尿病

生长激素(Growth Hormone,GH)是垂体前叶生长激素细胞分泌的一种多肽激素,由191个氨基酸组成,其分泌受下丘脑生长激素释放激素(Growth Hormone Releasing Hormone,GHRH)及下丘脑生长激素释放抑制因子(Somatostatin,SS)的控制.     

生长介素对肢端肥大症患者垂体瘤生长激素分泌影响的体外研究

作者在8例肢端肥大症体外培养的垂体GH瘤细胞上探讨IGF-1对GH分泌的反馈调节作用。10~(-7)mol IGF-1使3例垂体GH瘤细胞GH基础分泌抑制到对照的44.6％～52.4％(P<0.05),1例GH分泌增加134.9％(P<0.05),4例GH基础分泌没有明显改变,表明体外培养的垂体GH瘤有一半以上对IGF-1 3小的·的急性作用失去正常的GH分泌抑制反应。3例对IGF-1失去GH分泌抑制反应的垂体GH瘤细胞同时伴有GH对GHRH_(1-44)及(或)生长抑素激动剂SMS_(201-995)反应消失,提示部分垂体GH瘤细胞的IGF-1和某些下丘脑激素受体或受体后有异常。     

Growth hormone secretion in genetic large (LL) and small (SS) rats

We investigated whether genetic selection for growth influences pituitary GH secretion in two strains of rats, LL (large) and SS (small). Animals were bled every 15 min for 6 h via an indwelling atrial Silastic catheter, and GH levels were determined by RIA. LL and SS males displayed a low frequency, high amplitude episodic pattern of GH secretion, with surges of GH occurring at 3- to 4-h intervals, separated by trough periods of approximately 60-120 min. In contrast, LL females showed a high frequency, low amplitude pattern of GH secretion, with GH pulses occurring every 1-2 h. The number of GH pulses in SS females was lower than that in LL females. SS males and SS females displayed lower peak amplitudes and lower baseline levels and, therefore, lower mean plasma GH levels compared to LL animals. The anterior pituitary GH content was not significantly different in LL and SS animals of either sex. Thus, the reduction of GH levels in SS animals is most likely the result of reduced release of GH-releasing factor from the hypothalamus or an attenuated pituitary sensitivity to GH-releasing factor.     

The effect of hypophysectomy and growth hormone administration on pre-prosomatostatin messenger ribonucleic acid in the periventricular nucleus of the rat hypothalamus

Physiological evidence suggests that hypothalamic somatostatin (SS) inhibits pituitary GH release and that GH acts through a short-loop feedback mechanism to stimulate SS secretion. The feedback action of GH could be mediated by an effect on SS synthesis, secretion, or both. We hypothesized that GH acts to regulate the expression of the SS gene and that changes in the level of circulating GH would result in corresponding changes in SS mRNA in cells of the periventricular nucleus (PeN) of the hypothalamus. To test this hypothesis we measured the effect of hypophysectomy (HPX) and HPX with bovine GH (bGH) replacement on SS mRNA signal levels in cells of the PeN of the rat brain. We report that HPX male rats treated with bGH have significantly higher PeN SS mRNA signal than their vehicle-treated controls (P less than 0.05) and that bGH administration to sham-HPX rats results in elevated PeN SS mRNA signal levels compared to those in sham-HPX rats treated with vehicle (P less than 0.05). These observations suggest that GH participates in the regulation of its own secretion by influencing the expression of the SS gene and that one mechanism of short-loop pituitary feedback may involve the modulation of neuropeptide gene expression.     

Delayed release formulation of the somatostatin analog RC-160 inhibits the growth hormone (GH) response to GH-releasing factor-(1-29)NH2 and decreases elevated prolactin levels in rats

Recently, we have developed a long-acting delivery system for our somatostatin (SS) analog RC-160 based on injectable microcapsules in poly-(D,L-lactide-coglycolide). We studied the capacity of this formulation to repeatedly block the GH secretion induced by administration of GRF-(1-29)NH2 (GRF) on different days. Male rats anesthetized with pentobarbital were injected iv with 2.5 micrograms/kg BW GRF-(1-29)NH2 or saline. Five minutes later, blood samples were taken for GH measurement, and the animals were injected im with RC-160 microcapsules at a dose calculated to release 25 micrograms/day of the analog for 7 days or with the vehicle. The GRF stimuli were repeated 48 h, 96 h, and 8 days after administration of SS analog in microcapsules. GRF administration increased GH levels at the four times tested (P less than 0.01) in the control group injected with vehicle, while RC-160 microcapsules inhibited the GH response for more than 96 h (P less than 0.01). The GH levels augmented by pentobarbital were also decreased by the RC-160 microcapsules (P less than 0.01). Animals treated with microcapsules showed smaller increases in their body weight than untreated rats (P less than 0.05). We also investigated the effect of RC-160 microcapsules on hyperprolactinemic female rats implanted with pituitary glands under the kidney capsules. High PRL levels in rats bearing pituitary grafts showed a significant decrease when measured 4 days after the administration of RC-160 microcapsules. These results demonstrate the efficacy of the long-acting delivery system of the SS analog RC-160 and suggest the possible clinical usefulness of this formulation for lowering GH and PRL levels.     

A comparison of the effects of bromocriptine and somatostatin on growth hormone gene expression in the rat anterior pituitary gland in vitro

The effects of the dopamine agonist bromocriptine (BCR) have been compared with those of somatostatin (SS) on growth hormone (GH) synthesis and secretion by rat anterior pituitary cells in vitro. Both BCR and SS produced a dose-related reduction in GH release. Cytoplasmic GH mRNA levels were unchanged by BCR treatment and this finding was associated with an increase in total intracellular GH content. The reduction in GH release seen following SS treatment was accompanied by a fall in cytoplasmic GH mRNA levels and no significant change in intracellular GH content. These results suggest that the effects of BCR are predominantly on GH release mechanisms, whereas SS appears not only to regulate hormone release but also to regulate GH gene expression at a pre-translational level.     

The relative roles of continuous growth hormone-releasing hormone (GHRH(1-29)NH2) and intermittent somatostatin(1-14)(SS) in growth hormone (GH) pulse generation: studies in normal and post cranial irradiated individuals

OBJECTIVES: Pulsatile GH release in humans is thought to involve the coordinated interaction of growth hormone-releasing hormone (GHRH) and somatostatin (SS). Disordered GH secretion is seen in most patients following high dose (> 30 Gy) cranial irradiation in childhood and could result from dysregulation of these hypothalamic hormones or reflect direct pituitary damage. We have used a peptide 'clamp' to assess the relative roles of continuous GHRH and intermittent SS in GH pulse generation in healthy volunteers and short-and long-term survivors of childhood brain tumours. DESIGN: Randomized controlled study. PATIENTS: 12 adult male long-term survivors of childhood brain tumours (median age 17.0 years (15.2-19. 7); 12.2 years (5.8-14.0) postradiotherapy, > 30Gy whole brain irradiation) with 9 matched control volunteers and 6 short-term survivors of childhood brain tumours (median age 6.4 years (5.9-7. 7); 2.5 years (1.7-3.6) post radiotherapy, > 30Gy whole brain irradiation) with 6 matched controls (studies of spontaneous GH release alone). MEASUREMENTS: Serum GH concentrations in 24 h spontaneous GH profiles and during three 'clamp' studies: continuous GHRH(1-29)NH2 (60 ng/kg/minutes, subcutaneous infusion, 24 h); intermittent SS(1-14) withdrawal (20microg/m2/hour, intravenous infusion, 3 h on/1 h off, 2-3 cycles over 8-12 h); intermittent SS and continuous GHRH combined (2-3 cycles over 8-12 h). Data were analysed by spectral analysis, 'peak' and 'trough' determination and serial array averaging. RESULTS: In normal adults, discrete pulsatility was seen in all profiles of spontaneous GH secretion. Continuous GHRH amplified peak GH concentrations (median basal peak 21.1 mU/l vs. GHRH 62.0 mU/l, P = 0.008) whilst pulse timing remained unaffected. Rebound GH release following SS withdrawal alone was variable. Combining continuous GHRH with intermittent SS produced regular GH responses upon SS withdrawal (20.3 mU/l; range 2. 3-105.4). Heterogeneous patterns of spontaneous GH release were seen in the irradiated subjects. Spontaneous peak GH release was reduced in the children following irradiation (Irradiation 14.9 mU/l vs. Control 25.1 mU/l, P = 0.007). Peak GH concentrations were significantly amplified by GHRH in half of them. Adult long-term survivors had lower spontaneous GH concentrations and continuous GHRH amplified GH release in most subjects (Spontaneous 4.2 mU/l vs. GHRH 6.5 mU/l, P = 0.008) but peak concentrations remained far less than those of controls. Combining intermittent SS with continuous GHRH regularized GH release in many patients but the GH responses remained attenuated (4.6 mU/l; 2.5-17.5). CONCLUSION: GH pulsatility can be generated in normal volunteers by the combination of continuous GHRH and intermittent SS and provides indirect evidence for a role for GHRH in GH synthesis and replenishment of stored GH pools at times of high SS tone. Patterns of GH release in short-and long-term survivors of childhood brain tumours are heterogeneous suggesting that combined hypothalamic deficiencies of GHRH and SS occur following high dose radiotherapy. The attenuated GH release seen in long-term survivors compared to controls suggests that GH secretory dysfunction does not simply reflect reduced GHRH and SS secretion, and that trophic effects or pituitary damage may be important with time.     

Interaction of carp growth hormone-releasing factor and somatostatin on in vitro release of growth hormone in rainbow trout (Oncorhynchus mykiss).

Possible antagonism between somatostatin (SS) and carp growth hormone-releasing factor (GRF) on growth hormone (GH) secretion was examined by radioimmunoassay in a dispersed rainbow trout pituitary cell culture system. SS (3 nM) significantly antagonized carp GRF(1-29; 1 nM, 10 nM)-induced GH secretion. The slope of the dose-response curve for carp GRF(1-29) with SS was statistically different from that of carp GRF(1-29) alone (p less than 0.05) suggesting a noncompetitive antagonism of SS to carp GRF. The carp GRF(1-29) was also indicated to be a noncompetitive antagonist to SS (p = 0.056). Carp GRF(1-29; 100 nM) was unable to restore the inhibitory effect of SS on GH release after pre-exposure of SS (30 nM) to the pituitary cells. We conclude that SS antagonizes carp GRF on GH release at the pituitary level in rainbow trout and this antagonism is noncompetitive. SS has a postantagonism to carp GRF which may implicate some important physiological adaptations in teleosts.     

Effect of long-term corticosteroid administration on rat pituitary growth hormone and prolactin

In vitro corticosteroids stimulate GH synthesis by pituitary cells, while in vivo they suppress stimulated plasma GH levels. In this study we investigated in rats the effect of hydrocortisone administration for 2-4 weeks on pituitary GH content. Hydrocortisone added to the drinking water (100 mg/l) resulted in a marked stimulation of pituitary GH content after 3 and 4 weeks of treatment. No significant stimulation, however, was observed on basal GH release by the pituitary gland incubated in vitro. Further, we found that both Prl content and release were inhibited by hydrocortisone administration.     

Growth hormone (GH) autofeedback action in the neonatal rat: involvement of GH-releasing hormone and somatostatin

It is known that in adult rats, GH by itself and by promoting secretion of the somatomedins acts at the level of the hypothalamus to trigger release of somatostatin and decrease output of GH-releasing hormone (GHRH), thereby inhibiting further secretion of GH. To assess whether these mechanisms are already operative in the early postnatal period, we have evaluated the effect of short-term administration of GH in 10-day-old rats. Twice-daily s.c. administration of 25 micrograms human GH/rat, from days 5 to 9 of life, significantly reduced pituitary content of GH, decreased hypothalamic levels of GHRH mRNA and abolished the in-vivo GH response to a challenge dose of GHRH (20 ng/100 g body weight, s.c.). GHRH (20 ng/100 g body weight, twice daily, s.c.) given concomitantly with the GH treatment, completely counteracted the inhibitory effect of the latter on pituitary content of GH and restored to normal the in-vivo GH response to the GHRH challenge. These data indicate that impaired secretion of GHRH is involved in the inhibitory effect elicited by GH treatment in infant rats. However, concomitant involvement of hypothalamic somatostatin as a result of GH treatment cannot be ruled out. In fact, pituitaries from rats pretreated with GH responded in the same manner as pituitaries from control rats to the GHRH challenge in vitro.     

氟化钠对催乳素诱发分泌影响的体外研究

应用半侧垂体培养和腺垂体原代单层细胞培养方法观察了ＮａＦ对ＰＲＬ基础分泌和ＴＲＨ、ＶＩＰ及ｍｅｔｏｃｌｏｐｒｉａｍｉｄｅ诱发分泌的影响。结果是：１、氟中毒大鼠半侧垂体ＴＲＨ诱发的ＰＲＬ分泌降低。２、ＮａＦ对腺垂体细胞ＰＲＬ基础分泌和ＴＲＨ、ＶＩＰ和ｍｅｔｏｃｌｏｐｒａｍｉｄｅ诱发分泌均具有抑制作用。提示氟中毒时氟化物可能通过对垂体的直接作用而抑制ＰＲＬ分泌。