Role of the GH/IGF-I axis in the growth retardation of weaver mice

IGF-I is a well-established anabolic growth factor essential for growth and development. Although the role of the GH/IGF-I axis is established for normal postnatal growth, its functional state in neurodegenerative diseases is not fully characterized. The weaver mutant mouse is a commonly used model for studying hereditary cerebellar ataxia and provides an opportunity to investigate the function of IGF-I in postnatal growth following neurodegeneration. Previously, we reported that weaver mice are growth retarded and their body weights correlate with a decrease in circulating IGF-I levels. Because weaver mice have the same food intake/body weight ratios as their wild type littermates, our observation suggests that an impairment of the GH/IGF-I axis, rather than poor nutrition, likely contributes to their growth retardation. This study further investigated the etiology of reduced circulating IGF-I levels. We found that GH levels in weaver mice were reduced following acute insulin injection, but the hepatic GH receptor transduction pathway signaled normally as evidenced by increased STAT5b phosphorylation and IGF-I mRNA levels in response to acute GH administration. In addition, 2-week GH treatment induced a significant increase in body weight and circulating IGF-I levels in homozygous weaver mice but not in wild type littermates. In summary, a deficiency in the GH/IGF-I axis may be partially responsible for postnatal growth retardation in weaver mutant mice. This deficiency may occur at the level of the pituitary and/or hypothalamus and can be improved with GH administration.     

Anxiolytic-like effects of oleamide in group-housed and socially isolated mice

Oleamide (cis-9,10-octadecenoamide) is an endogenous sleep-inducing lipid and prototypic member of a new class of biological signaling molecules identified in recent years. In the present study, the anxiolytic-like effect of oleamide was studied in several experimental models of anxiety in group-housed and socially isolated mice. As the results show, socially isolated mice exhibited an anxiogenic-like profile in the elevated plus-maze test, the light/dark test, and the hole-board test, which could be significantly reversed by oleamide (10 or 20 mg/kg, i.p.). Moreover, oleamide significantly reduced the anxiety levels in grouped-housed mice. In the isolation-induced aggressive test, oleamide markedly reduced the attacking duration and increased the attacking latency. It is concluded that oleamide has an anxiolytic-like effect in socially isolated or group-housed mice, which suggests that fatty acid amides might be involved in the regulation of anxiety-related behavior in mice.     

Gut hormones and appetite control

Many peptides are synthesized and released from the gastrointestinal tract. Although their roles in the regulation of gastrointestinal function have been known for some time, it is now evident that they also physiologically influence eating behavior. Our understanding of how neurohormonal gut-brain signaling regulates energy homeostasis has advanced significantly in recent years. Ghrelin is an orexigenic peptide produced by the stomach, which appears to act as a meal initiator. Satiety signals derived from the intestine and pancreas include peptide YY, pancreatic polypeptide, glucagon-like peptide 1, oxyntomodulin, and cholecystokinin. Recent research suggests that gut hormones can be manipulated to regulate energy balance in humans, and that obese subjects retain sensitivity to the actions of gut hormones. Gut hormone-based therapies may thus provide an effective and well-tolerated treatment for obesity.     

Aging defined by a chronologic-replicative protein network in Saccharomyces cerevisiae: An interactome analysis

Aging is a multifactorial condition that results in the loss of an organism's fitness over time. Different theories have been formulated to explain the mechanisms of aging, but a synthesis of these theories has not been possible until now. In addition, the increase in molecular data gathered by proteomics projects utilizing different organisms has permitted a better picture of proteins that function in aging. In this sense, the yeast Saccharomyces cerevisiae is a biological model for aging, and it shows two distinct aging states: a replicative state termed the replicative lifespan (RLS) and a quiescent state known as the chronological lifespan (CLS). Interestingly, both RLS and CLS appear to share common groups of proteins, but a combined model of both aging mechanisms has not been defined. Thus, by applying systems biology tools that allow mining of the yeast proteins associated with aging, it was possible to obtain an interactome network in which both RLS and CLS are represented. In addition, four subgraphs comprising ubiquitin-dependent proteasome/regulation of cell growth, nucleic acid metabolism, carbohydrate metabolism/RNA metabolism, and carbohydrate-organic acid-amino acid/DNA metabolism were found within the interactome, defining a new model of aging for yeast termed the chronologic-replicative protein network (CRPN).     

PKC mediates GnRH activation of a Na/H exchanger in goldfish somatotropes

Previous results suggest that gonadotropin-releasing hormone (GnRH) stimulation of somatotropin secretion in goldfish involves activation of Na⁺/H⁺ exchange (NHE). We tested the hypothesis that GnRH alkalinizes intracellular pH (pH_i) via protein kinase C (PKC) activation of NHE. Two types of alkalinization responses were observed in identified goldfish somatotropes preloaded with the pH-sensitive dye BCECF; the rate of pH_i changes went from a neutral or slightly negative slope to either a positive or a less negative slope relative to control. Two GnRHs, the PKC-activating TPA, and dioctanoyl glycerol each caused an alkalinization in 70-90% of somatotropes. The PKC inhibitors, Bis II and Gö6976, the NHE inhibitor amiloride, or Na⁺-free solution attenuated TPA and GnRHs actions, suggesting that PKC mediates GnRH activation of NHE. Since amiloride and Na⁺-free solution caused acidification in somatotropes at rest, regulation of basal pH_i in these cells likely involves Na⁺ flux through amiloride-sensitive NHE.     

GH对创伤与感染SD大鼠IGF-1水平及营养代谢的影响

目的　探讨创伤与感染及外源性生长激素对SD雄性大鼠血清胰岛素样生长因子-1(IGF-1)及营养代谢的影响。　方法　SD雄性大鼠60只，随机分成生长激素治疗组和对照组(各30只)，复制成腹腔感染动物模型，治疗组术后第1天开始给予GH0.5U     

Ghrelin levels are reduced in Rett syndrome patients with eating difficulties

Most patients with Rett syndrome (RTT) have both gastrointestinal problems and somatic growth failure, including microcephaly. Ghrelin is a peptide hormone involved in growth hormone secretion, interdigestive motility, and feeding behavior. Plasma ghrelin assays have previously been described for other neurodevelopmental disorders. To examine the pathophysiology of RTT, we measured plasma levels of ghrelin in patients with RTT. A case-control study examining plasma levels of ghrelin, serum growth hormone, and insulin-like growth factor-1 (IGF-1) was performed on 27 patients with RTT and 53 controls. Plasma levels of total (T)- and octanoyl (O)-ghrelin were significantly lower in patients with RTT than in controls. Plasma levels of T-ghrelin correlated significantly with serum IGF-1 levels and head circumference. Significantly lower levels of plasma T-ghrelin and O-ghrelin were observed in RTT patients with eating difficulties, while lower levels of plasma T-ghrelin were observed in RTT patients with constipation, in comparison to patients without either of these symptoms. Alterations in plasma ghrelin levels may reflect various clinical symptoms and signs in RTT patients, including growth failure, acquired microcephalus, autonomic nerve dysfunction, and feeding difficulties. We describe the role of ghrelin in RTT and suggest this peptide as a novel biological marker in patients with RTT.