Secretogranin I (chromogranin B) mRNA accumulation is hormonally regulated in GH3B6 rat pituitary tumor cells

Secretogranin I (SgI; chromogranin B) belongs to a class of acidic tyrosine-sulfated secretory proteins believed to play a role in the secretory process of endocrine cells. Our aim here was to compare the levels of SgI mRNA to that of prolactin (PRL) and growth hormone (GH), using rat pituitary cell lines. As far as the constitutive expression is concerned, we found a positive correlation between SgI mRNA and PRL mRNA levels. However, the neuropeptide TRH (50 nM) inhibited the accumulation of SgI mRNA in GH3B6 cells whereas, as expected, it induced a rapid and sustained increase in PRL mRNA accumulation. By contrast, 17β-estradiol (1 nM) stimulated the accumulation of both SgI and PRL mRNAs, with the same EC₅₀ (18–59 pM). Reciprocally, treatment with dexamethasone (100 nM) reduced the level of SgI and PRL mRNAs to 23% and 29% of control, respectively, but led to a 2.1-fold increase in the GH mRNA level. Altogether, the present work shows that SgI gene expression is subject to multiple hormonal regulations and occasionally parallels the regulation of the PRL gene but never that of the GH gene, under the conditions tested.     

Interactions between growth hormone and dexamethasone in skeletal growth and bone structure of the young mouse

Summary The present study investigated the interactions of growth hormone (GH) and glucocorticoid on skeletal growth and bone structure in young mice. The purpose of this study was to examine the possible prevention by GH of the damage inflicted by dexamethasone (Dex) at sites of skeletal growth and ossification. Dex (1 mg/kg) with or without rat GH (rGH) or bovine GH (bGH), 1 mg/kg, was given for 4 weeks, from age 3–7 weeks, to female ICR mice. Tibiae, humerus, and vertebrae were analyzed morphometrically and biochemically. Growth, as determined by the mouse weight, tibial length, and humerus protein content was found to be compromised by dexamethasone. This was prevented by rGH or bGH. The epiphyseal growth plate width, trabecular bone volume, cortical bone width, mineral bone content, and alkaline and acid phosphatase activity were decreased by dexamethasone. These were prevented by rGH or by bGH. The findings of the present study suggest that in the mouse, GH can decrease or even avoid some of the pathological features in growing bones inflicted by high-dose glucocorticoid treatment.     

Selective modification at the N-terminal region of human growth hormone that shows antagonistic activity

A new analogue of recombinant human growth hormone (hGH), hGH des(1–6,14) was expressed in Escherichia coli, refolded and purified to homogeneity. The mutation decreased the hormone's ability to bind lactogenic and somatogenic receptors through its site 1, and almost completely abolished its ability to bind these receptors through site 2, as evidenced by both binding and gel-filtration experiments. More specifically, the binding to prolactin receptors (PRLRs) from various species or their soluble recombinant extracellular domains (ECDs) was decreased 1.5–4-fold, whereas the binding to hGH receptor (hGHR) was decreased 10–85-fold. These changes caused an almost total loss of hormone agonistic activity in several in vitro bioassays and subsequently, the hGH des(1–6,14) analogue acquired antagonistic properties. This antagonistic activity was dependent upon modification of site 1. In those cases in which the binding was reduced only slightly, e.g. binding to rabbit PRLRs, hGH des(1–6,14) acted as a strong antagonist, whereas in others in which the binding of site 1 was reduced to a higher degree, such as other PRLRs and, in particular, hGHR, the antagonistic activity was correspondingly weaker. Circular dichroism spectra of the analogue suggested that these changes do not result from a decrease in overall -helix content, but rather from minor local structural modifications at the N-terminus.     

抗人甲状腺过氧化物酶抗体与其他自身抗体的关系

甲状腺过氧化物酶（ＴＰＯ）是甲状腺微粒体的抗原成分。在纯化抗原建立测定抗ＴＰＯ抗体ＥＬＩＳＡ法的基础上，并对抗ＴＰＯ与其他自身抗体的伴随关系作了研究。发现除自身免疫性甲状腺病有较高阳性率外，ＳＬＥ等患者抗ＴＰＯ检出率也很高（１０％￣５２．１％），且抗ＴＰＯ阳性者，抗核抗体等其他自身抗体的阳性率也高达３０．８％￣９５．２％。抗ＴＰＯ抗体与其他自身抗体的相关系数ｒ＝０．７４６７（Ｐ〈０．０１）。     

Relationship between growth hormone and Somatomedin-C levels in untreated acromegaly, after surgery and radiotherapy and during medical therapy with Sandostatin (SMS 201–995)

Abstract. Several conflicting reports have been published with regard to the relationships between circulating growth hormone (GH), Somatomedin-C (SM-C) levels and clinical activity during different stages of therapy of acromegaly. We did not find a significant correlation between (fasting, post-prandial and mean 24-h) plasma GH and SM-C concentrations in twenty-two untreated acromegalic patients. There was a statistical significant correlation, however, if only the GH levels below 100 μg l^-1 were considered (n=18 patients, P<0·01). The distribution of molecular forms of GH (‘little’, ‘big’ and ‘big-big’) did not differ between the four patients with GH levels above 100 μg l^-1 and in four patients with levels between 40 μg l^-1 and 80 μg l^-1. Therefore, it is suggested that GH levels of 80–100 μg l^-1 maximally activate Somatomedin-C production in man and that further increases in GH in general will not result in a further increase in SM-C generation. There was a significant correlation between GH and SM-C levels in forty-nine acromegalic patients after surgery and/or radiotherapy (P<0·001). In twenty-three of thirty-one patients with elevated SM-C levels the disease was subjectively still active, while this was the case in none of the patients with normal SM-C levels. In eight patients the disease was considered not to be clinically active any more, despite slightly increased SM-C levels. During long-term therapy of ten acromegalic patients for 16–108 weeks (mean 66±10) with 200–300 μg Sandostatin subcutaneously, clinical activity of the disease disappeared well before mean 24–h GH and SM-C levels reached the normal levels. There was a close correlation between mean 24-h GH and SM-C levels during Sandostatin therapy (P<0·001). ‘Clinical cure’ during this medical treatment was reached in five patients, as reflected by disappearance of subjective complaints, normalization of SM-C levels and 24-h mean GH levels of 2·8±0·2 μg l^-1. Conclusions: (i) in untreated acromegaly, circulating GH and SM-C levels correlate well up to GH concentrations of 100 μg l^-1. A further increase in GH does not result in a corresponding further increase in SM-C levels, suggesting a maximally activated production, without further GH-dependent capacity. (ii) Clinical ‘cure’ of acromegaly often occurs before normalization of the circulating SM-C levels. (iii) The measurement of plasma SM-C concentrations can be used well to adjust the dose and frequency of Sandostatin administration in acromegaly. This avoids the need of measuring extensive 24-h GH profiles.     

荔枝果实发育期间内源激素含量动态

本研究测定了荔枝果实发育期间内源激素含量的动态。结果表明果实发育前期细胞分裂素(CTK),生长素(IAA)含量较高;中期乙烯(Eth),赤霉素(GA),的含量较高,这与果实的生长发育及落果有密切相关。同时,果实发育前期应用外源CTK、中期应用GA、处理果穗可显著提高产果率。     

The effects of intermittent administration of human parathyroid hormone (1–34) on streptozotocin-induced diabetic rats

Intermittent administration of low doses of human parathyroid hormone (h-PTH) has been reported to exhibit an anabolic effect on bone, increasing its mass. We investigated the effects of intermittent administration of h-PTH on bone changes in streptozotocin- (STZ-) induced diabetes mellitus (DM) rats by measuring bone mineral density and bone mineral contents and by bone histomorphometry. Wistar rats, 7–8 months old, were used. Osteoporosis was induced by diabetes mellitus, which was established by an intraperitoneal injection of STZ. Rats were separated into five groups: sham-injected, baseline control, vehicle-only-administered, and low-dose (6.0μg/kg) or high-dose (60.0μg/kg) h-PTH-administered groups. h-PTH or vehicle was injected subcutaneously six times a week for 4 weeks beginning 9 weeks after STZ administration. Bone mineral density and mineral contents were significantly lower in the baseline control and vehicle groups than in the control group. The PTH-administered groups showed higher values compared with both vehicle and baseline control groups. In bone histomorphometry, both bone volume and bone formation in the STZ group were markedly reduced. The h-PTH-administered rats showed increase in both bone volume and bone formation, which are related parameters, but administration of h-PTH did not alter the extent of eroded surface. Our results suggest that intermittent administration of h-PTH is effective in activating bone formation and in preventing further bone loss in osteoporosis developed by STZ-induced DM.     

大鼠实验性肝硬化时甲状腺激素水平及甲状腺形态学变化的研究

将Wistar大鼠分为三组：肝硬化组，给予四氯化碳等复合因素，给药组，除给CCl4等复合因素外，用赤栀黄合剂灌胃41天；正常组给以一般饮食及饮水。结果，与正常组及给药组相比，硬化组血T3、T4测定值低，甲状腺滤泡中胶质明显减少，滤泡细胞与胶质间空泡增多，滤泡上皮细胞内PAS阳性小滴数日增多。表明在实验性肝硬化期间甲状腺参与了抗疾病的代谢活动，其机理可能是肝硬化时肝细胞合成、转运T3，T4的蛋白质减少。运输中的T3，T4减少，活性甲状腺素不足，从而导致甲状腺代偿性功能活跃。赤栀黄合剂具有保肝，恢复甲状腺素水平的作用。     

不同置换液量血液透析滤过治疗尿毒症皮肤瘙痒疗效观察

目的：观察不同置换液量血液透析滤过(HDF)对尿毒症皮肤瘙痒的治疗作用。方法：将30例并发皮肤瘙痒的维持性血液透析尿毒症患随机分为三个组，分别接受高置换液量后稀释HDF(置换液20L)、低置换液量后稀释HDF(置换液10L)和高通量血液透析治疗。均使用F60透析器，隔日1次，连续3次，其余治疗条件相同。对皮肤瘙痒症状定量计分，比较三组病人治疗前后皮肤瘙痒症状积分的改变以及血磷和甲状旁腺激素(PTH)的变化。结果：高置换液量HDF组治疗后皮肤瘙痒积分明显下降，有统计学意义。其余两组无差异。以皮肤瘙痒积分下降50％为有效计算，高置换液量HDF组7例有效，有效率70％；低置换液量HDF组3例有效。有效率30％；透析组1例有效，有效率10％。三组间比较有统计学差异。三组透析后血磷均明显下降，有统计学意义；PTH亦有下降，HDF组有统计学差异，HD组无统计学差异。结论：增加置换液量可以提高HDF治疗尿毒症皮肤瘙痒的疗效；HDF治疗尿毒症皮肤瘙痒疗效优于高通量血液透析；HDF清除PTH的效果高于HD。     

Female sexual receptivity is defective in juvenile hormone-deficient mutants of theapterous gene ofDrosophila melanogaster

During reproductive maturation of female insects, the acquisition of sexual receptivity is coordinated with ovarian development. Juvenile homone regulates vitellogenesis in the ovaries, but the action of this hormone in the development of sexual behavior is less well-understood. A strain ofDrosophila melanogaster carrying a mutation in theapterous gene(ap ⁴) was known to exhibit arrested vitellogenesis (rescuable by applying exogenous juvenile hormone), sterility of both sexes, and a deficiency of juvenile hormone. In this study, we examined the effects of mutations ofap on female receptivity and its relationship to juvenile hormone. We observed abnormally low female receptivity in homozygousap strains, and heteroallelic combinations ofap mutations exhibited low receptivity. For female receptivity,ap showed no dominance (i.e.,ap/ap ⁺ was intermediate betweenap/ap andap ⁺/ap ⁺). Low receptivity mapped genetically to theap locus. The reduction in female receptivity in these mutants is positively correlated with levels of juvenile hormone synthesized by their corpora allata.This work was supported in part by The Scheinfeld Center for Humans Genetics in the Social Sciences (J.R.), The National Science Foundation (BNS-882 1339 to J.R.), BARD (No. IS-1664-89R to D.S.), The Israel Cancer Research Fund (grant to D.S.), The Rekanati Foundation of Tel Aviv University (grant to D.S.), and The Israeli Fruit Council (award to M.A.)