Growth hormone-releasing factor: direct effects on growth hormone, glucose, and behavior via the brain

Intracerebroventricular administration of human pancreatic growth hormone-releasing factor caused a dose-dependent inhibition of growth hormone secretion, elevated plasma glucose concentrations, and produced marked behavioral and motor effects. Immunoneutralization with antiserum to somatostatin did not reverse the suppression of growth hormone. These findings suggest that hypothalamic growth hormone-releasing factor may regulate its own neurosecretion through an "ultrashort-loop" negative feedback mechanism and may have important neurotransmitter and neuromodulatory functions in the brain.     

Potent interaction between glucocorticoids and growth hormone-releasing factor in vivo

Administration of dexamethasone significantly enhanced the pituitary growth hormone response to growth hormone-releasing factor in intact as well as adrenalectomized rats. Thus the inhibitory effects of glucocorticosteroids on somatic growth which involve an interaction of these steroids and growth hormone at a peripheral level may also involve a modification of pathways within the central nervous system that regulate normal growth hormone secretion.     

Receptor-associated resistance to growth hormone-releasing factor in dwarf "little" mice

Anterior pituitaries from the dwarf mouse strain "little" did not release growth hormone or accumulate adenosine 3',5'-monophosphate (cyclic AMP) in response to human and rat growth hormone-releasing factor (GRF). Dibutyryl cyclic AMP, as well as the adenylate cyclase stimulators forskolin and cholera toxin, markedly stimulated growth hormone (GH) release. The basis of the GH deficiency in the little mouse may therefore be a defect in an early stage of GRF-stimulated GH release related either to receptor binding or to the function of the hormone-receptor complex.     

Patterns of growth hormone-releasing factor and somatostatin secretion into the hypophysial-portal circulation of the rat

The interrelation between the secretion of two hypophysiotropic peptides, growth hormone-releasing factor (GRF) and somatostatin (SRIF), in the generation of episodic growth hormone (GH) secretion was inferred from direct measurements of immunoreactive GRF and immunoreactive SRIF concentrations in the hypophysial-portal plasma of the rat. Secretion of immunoreactive GRF was found to be episodic, with maximal concentrations present during periods of expected GH secretory episodes. Secretion of immunoreactive GRF was accompanied by a moderate reduction in portal plasma levels of immunoreactive SRIF. Passive immunoneutralization of SRIF was associated with increased concentrations of immunoreactive GRF in hypophysial-portal plasma. On the basis of these observations, it appears that each GH secretory episode is initiated by pulsatile secretion of immunoreactive GRF into the portal circulation, which is preceded by or is concurrent with a moderate reduction of inhibitory tone provided by portal immunoreactive SRIF. These experiments provide direct insights into central and adenohypophysial mechanisms by which GRF and SRIF interact to generate episodic secretion of GH.     

Nerve growth factor gene expression in the developing rat brain

The regulation of nerve growth factor (NGF) protein and NGF messenger RNA (mRNA) in the developing rat brain has been studied to assess the hypothesis that NGF supports the differentiation of cholinergic neurons in the basal forebrain. In the adult, the major targets of these neurons, the hippocampus and neocortex, contain the highest concentrations of NGF mRNA, but comparatively low ratios of NGF protein to its mRNA. In contrast, a high concentration of NGF protein and a low concentration of NGF mRNA were seen in the basal forebrain, consistent with retrograde transport of NGF protein into this region from the neocortex and hippocampus. In these two target regions NGF and NGF mRNA were barely detectable at birth, their concentrations increased to a peak at day 21, and then NGF mRNA, but not NGF protein, declined threefold by day 35. NGF accumulation in the basal forebrain paralleled that in the target regions and preceded an increase in choline acetyltransferase, suggesting that the differentiation of cholinergic projection neurons is indeed regulated by retrogradely transported NGF. In addition, high ratios of NGF protein to NGF mRNA, comparable to that in the basal forebrain, were seen in the olfactory bulb and cerebellum, suggesting that NGF may be transported into these regions by unidentified neurons.     

Physiological effects of transforming growth factor in the newborn mouse

Transforming growth factor-type alpha accelerated incisor eruption and eyelid opening in the newborn mouse and also retarded the growth rates of hair and body weight when administered in high dosage (0.7 to 4 micrograms per gram of body weight). The results of whole animal studies indicate that transforming growth factor-type alpha and epidermal growth factor do not differ significantly in these effects and suggest that transforming growth factor-type alpha may be important in immature animals.     

Induction of mating behavior in rats by luteinizing hormone-releasing factor

Ovariectomized female rats treated with estrogen, in dosages too low to provoke mating, displayed this behavior when given subcutaneous injections of synthetic luteinizing hormone-releasing factor (LRF) 48 hours later. Two hours after the injection of LRF, components of female sexual behavior appeared. The lordosis reflex followed mounting by the male, and darting and hopping behavior was quite prevalent. On the other hand, treatment with estrogen followed by luteinizing hormone, follicle-stimulating hormone, or thyrotropin-releasing factor did not induce copulatory behavior. The results suggest that LRF may play a role in induction of mating behavior.     

Nerve growth factor treatment after brain injury prevents neuronal death

Cholinergic neuronal degeneration after axotomy has been proposed to be due to the loss of a retrogradely transported neurotrophic factor, possibly nerve growth factor (NGF). To test this hypothesis, NGF was continuously infused into the lateral ventricles of adult rats that had received bilateral lesions of all cholinergic axons projecting from the medial septum to the dorsal hippocampus. After 2 weeks of NGF treatment, identification of cholinergic neurons by the presence of the biosynthetic enzyme choline acetyltransferase revealed a dramatic increase (350%) in the survival of the axotomized septal cholinergic neurons. Thus, NGF or an NGF-like molecule can act as a neurotrophic factor for these neurons.     

Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation

Closely related signals often lead to very different cellular outcomes. We found that the differentiation of human mesenchymal stem cells into bone-forming cells is stimulated by epidermal growth factor (EGF) but not platelet-derived growth factor (PDGF). We used mass spectrometry-based proteomics to comprehensively compare proteins that were tyrosine phosphorylated in response to EGF and PDGF and their associated partners. More than 90% of these signaling proteins were used by both ligands, whereas the phosphatidylinositol 3-kinase (PI3K) pathway was exclusively activated by PDGF, implicating it as a possible control point. Indeed, chemical inhibition of PI3K in PDGF-stimulated cells removed the differential effect of the two growth factors, bestowing full differentiation effect onto PDGF. Thus, quantitative proteomics can directly compare entire signaling networks and discover critical differences capable of changing cell fate.     

Luteinizing hormone-releasing factor potentiates lordosis behavior in hypophysectomized ovariectomized female rats

Subcutaneous injection of luteinizing hormone-releasing factor (LRF) in estrogen-primed hypophysectomized, ovariectomized female rats facilitates the appearance of the lordosis response. The LRF effect on lordosis was seen 90, 180, and 360 minutes after injection. This effect could help to synchronize the female's mating behavior with the ovulatory discharge of luteinizing hormone.     

胎盘生长因子在结核性胸腔积液中的表达及其与治疗效果的关系

目的 探讨胎盘生长因子(P1GF)在结核性胸腔积液中的表达及其与治疗效果的关系.方法 检测56例结核性胸膜炎合并胸腔积液患者血清和胸腔积液中P1GF的表达水平,根据胸部CT检查结果将患者分为胸膜增厚组17例和未增厚组39例,分析胸腔积液中PIGF含量与胸膜增厚、胸水吸收时间及患者一般资料的关系.结果 胸膜增厚组胸腔积液中P1GF水平为(1114.59±120.69) ng/L,明显高于胸膜未增厚组的(878.61±116.57) ng/L,差异有统计学意义(P＜0.01),根据积液吸收时间将患者分为3组:胸水吸收时间＜2周18例,2～4周30例,＞4周8例,P1GF水平分另别为(945.56±92.46)、(1080±152.43)、(1138±218.38) ng/L,3组比较差异有统计学意义(P＜0.01),胸腔积液中P1GF表达水平与患者胸水总蛋白量呈正相关(r=0.269,P＜0.05).结论 在结核性胸腔积液患者的P1GF表达水平与胸膜增厚、胸水吸收时间及胸水总蛋白量关系密切,机制可能是P1GF通过刺激胸膜血管生成和渗透性增加而促进结核性胸膜炎病情的进展.     

Paraoxon: effects on rat brain cholinesterase and on growth hormone and prolactin of pituitary

Cholinesterase activity of brain and content of growth hormone and prolactin in the pituitary were compared after short-term (3 days) and long-term (14 days) treatment with paraoxon in male and female rats. Within 3 days cholinesterase activity was reduced to between 5 and 15 percent of that in controls. The content of growth hormone in the pituitary was increased in long-term experiments by 50 percent. This increase in paraoxon-treated animals-suggests a possible role of a cholinergic mechanism in the regulation of growth hormone secretion.     

Trophic stimulation of cultured neurons from neonatal rat brain by epidermal growth factor

Epidermal growth factor (EGF) is a potent polypeptide mitogen originally isolated from the adult male mouse submaxillary gland. It also acts as a gastrointestinal hormone. EGF-immunoreactive material has recently been identified within neuronal fibers and terminals in rodent brain. In the present study, EGF was found to enhance survival and process outgrowth of primary cultures of subneocortical telencephalic neurons of neonatal rat brain in a dose-dependent manner. This effect was observed with EGF concentrations as low as 100 picograms per milliliter (0.016 nanomolar) and was dependent on the continuous presence of EGF in the medium. Similar effects were observed with basic fibroblast growth factor, but several other growth-promoting substances, including other mitogens for glial elements, were without effect. Thus EGF, in addition to its mitogenic and hormonal activities, may act as a neurite elongation and maintenance factor for select neurons of the rodent central nervous system.     

Fetal brain growth: selective action by growth hormone

Growth hormone was administered to pregnant rats maintained under dietary control, and fetal and placental growth and nutrition were examined. Growth hormone had a selective action on brain growth that could not be attributed to nutrient mobilization but suggested a trophic factor which is unique to the brain.