The roles of placental growth hormone and placental lactogen in the regulation of human fetal growth and development

The human growth hormone (hGH)/human placental lactogen (hPL) gene family, which consists of two GH and three PL genes, is important in the regulation of maternal and fetal metabolism and the growth and development of the fetus. During pregnancy, pituitary GH (hGH-N) expression in the mother is suppressed; and hGH-V, a GH variant expressed by the placenta, becomes the predominant GH in the mother. hPL, which is the product of the hPL-A and hPL-B genes, is secreted into both the maternal and fetal circulations after the sixth week of pregnancy. hGH-V and hPL act in concert in the mother to stimulate insulin-like growth factor (IGF) production and modulate intermediary metabolism, resulting in an increase in the availability of glucose and amino acids to the fetus. In the fetus, hPL acts via lactogenic receptors and possibly a unique PL receptor to modulate embryonic development, regulate intermediary metabolism and stimulate the production of IGFs, insulin, adrenocortical hormones and pulmonary surfactant. hGH-N, which is expressed by the fetal pituitary, has little or no physiological actions in the fetus until late in pregnancy due to the lack of functional GH receptors on fetal tissues. hGH-V, which is also a potent somatogenic hormone, is not released into the fetus. Taken together, studies of the hGH/hPL gene family during pregnancy reveal a complex interaction of the hormones with one another and with other growth factors. Additional investigations are necessary to clarify the relative roles of the family members in the regulation of fetal growth and development and the factors that modulate the expression of the genes.     

Thyroid hormones and nervous system development

Regulation by hormones of nervous system development is well recognized in humans, laboratory animals and cultured nerve cells. Thyroxine (T4) and triiodothyronine (T3), the major thyroid hormones, act on brain development and maturation by binding to T3 nuclear receptors. T3 responsive genes have been identified with the T3 receptor as a superfamily of genes including cortisol and estrogens, necessary for adaptation and survival. Less defined are T3 and T4 actions on the peripheral nervous system. In chromaffin cells explanted from the adrenal of immature rats, T3 induces the enzyme tyrosine hydroxylase, involved in catecholamine synthesis. This action is similar but, so far, apparently independent from Nerve Growth Factor promotion of sympathetic and chromaffin cell growth. Mechanisms based on nuclear binding depend on multiple receptors functionally diversified; their selectivity of action over a wide range of early and late developmental patterns is an attractive hypothesis to be further explored.     

The insulin receptor

Cells are endowed with specific cognitive molecules that function as receptors for hormones, neurotransmitters, and other intercellular messengers. The receptor molecules may be present in the plasma membrane, cytoplasm, or nucleus. When occupied by the messenger, the receptor is coupled to the cellular machinery that responds to the message-bearing molecules. For some hormones the events following attachment of the messenger to the receptor are well known. An example is the generation of cAMP after combination of glucagon with its receptor and the series of steps culminating in activation of phosphorylase. In the case of many other messengers, including insulin, the nature of these coupling steps is not known. Receptors are subject to the regulatory processes of synthesis, degradation, and conformational change; alterations in receptor properties may have significant effects on the qualitative and quantitative responses of the cell to the extracellular messenger. The insulin receptor is located in the plasma membrane, is composed of two pairs of subunits, and has a molecular weight of about 350,000. It is located in cells such as adipocytes, hepatocytes, and skeletal muscle cells as well as in cells not considered to be typical target organ cells. Insulin receptors in nonfetal cells are downregulated by exposure of the cells to high concentrations of insulin. Other factors that regulate insulin binding include muscular exercise, diet, thyroid hormones, glucocorticoids, androgens, estrogens, and cyclic nucleotides. The fetus has high concentrations of insulin receptors in several tissues. These begin to appear early in fetal life and may outnumber those found in adult tissues. Fetal insulin receptors are unusual in that they may not undergo downregulation but may experience the opposite when exposed to insulin in high concentrations. Thus the offspring of a mother with poorly controlled diabetes may be placed in double jeopardy by fetal hyperinsulinemia and augmented insulin binding by the receptors. Many disorders in children and adults are associated with changes in the properties of the insulin receptor. In general, the alterations have been measured in receptor-bearing cells that are readily accessible, such as circulating monocytes and erythrocytes. The receptors on these cells generally reflect the status of receptors on the major target organs of insulin, although exceptions are known, and conclusions drawn from studies of receptors on circulating cells must be made with caution.(ABSTRACT TRUNCATED AT 400 WORDS)     

IgE response and its regulation in allergic diseases

The distinguishing feature of the allergic person is his or her elevation of serum IgE. This propensity to develop a sustained IgE response is determined genetically. The biologic effects of IgE are mediated via Fc receptors (Fc epsilon R) present on mast cells and basophils (Fc epsilon R type 1) and subpopulations of monocytes, macrophages, eosinophils, and platelets (Fc epsilon R type 2). Interaction of allergen with IgE on these cells results in receptor "bridging" and the release of histamine and other inflammatory mediators. Fc epsilon R type 2 on lymphocytes and monocytes are upregulated in atopic disease and may play a role in the allergic inflammatory reaction. The activation of B cells to synthesize IgE requires several stages (see Fig. 2). T cells play an important role in the regulation of IgE synthesis. In vitro activation of resting B cells to synthesize IgE requires direct cellular interaction with T cells or the presence of IL4 for activation. The latter effect is inhibited by alpha-interferon. Preactivated B cells are influenced in an isotype-specific manner by T-cell-derived IgE binding factors (IgE-BF), which may act as IgE-potentiating or IgE-suppressive factors, depending on their degree of glycosylation. The regulation of IgE synthesis is an important area of investigation. It provides us with an understanding of the basis of the human allergic response and ultimately may provide the basis for novel strategies in the treatment of allergic diseases.     

Molecular mechanisms underlying insulin-like growth factor action: How mutations in the GH: IGF axis lead to short stature

Insulin-like growth factors (IGFs) act via the Type 1 IGF receptor (IGF-1R) to promote growth and development. Recent structural and site-directed mutagenesis studies have provided detailed insight into the mechanism of interaction between the IGFs and the IGF-IR. Studies of the insulin: insulin receptor interaction have provided important additional understanding of the mechanisms underlying the IGF:IGF-1R interaction. The recent crystal structure of the insulin receptor ectodomain showed a folded over conformation accommodating two potential ligand binding pockets. The ligand interacts with the receptor at two different sites within a binding pocket to achieve high affinity binding and activation of the receptor. In this review the effect of mutations in the human IGF1 and IGF-1R genes so for reported are explained in terms of the effect on ligand binding and receptor activation. The severity of patient phenotype can generally be correlated to the effect of the mutation on protein structure and function.     

Human placenta as a source of neuroendocrine factors

Progress in the understanding of the physiological and pathological functions of the placenta introduced the concept that the placenta is a neuroendocrine organ, since it shows local production and release of substances analog to neurohormones. These products act as endocrine, paracrine and autocrine factors to control the secretion of other regulatory molecules, including the pituitary hormones of both mother and fetus and their placental counterparts. Furthermore, they may play a role in the regulation of maternal and fetal physiology during pregnancy, ranging from the control of placental anchoring to fetal growth and maturation, fine regulation of uterine blood flow and/or initiation of labor. All this evidence underlines the decisive contribution of the placenta to all phases of gestation, through a range of substances largely exceeding the classically known sex steroids and chorionic gonadotropin, throughout normal pregnancy as well as in the presence of gestational diseases.     

The role of eicosanoids in paediatrics

Prostanoids are unsaturated cyclic fatty acids, are synthesized primarily from arachidonic acid, and, like the leukotrienes, belong to the growing family of eicosanoids. As tissue hormones, prostanoids act on specific receptors near their site of synthesis and degradation. Prostanoids operate as modulators and mediators in a large spectrum of physiological processes. They are involved in the regulation of maternal and fetal circulation, patency of the ductus arteriosus, plateletvessel wall interaction and kidney function. Besides their physiological function in protecting organ perfusion under stress conditions, they are also involved in diseases as described in the hyperprostaglandin E₂-syndrome or — together with leukotrienes-in inflammatory processes. More specific pharmacological tools than the nonsteroidal antiinflammatory drugs, such as receptor antagonists, selective synthesis inhibitors, and eicosanoid analogues offer the prospect of enriching our arsenal of pharmacotherapeutic interventions in a variety of diseases. Before active intervention, however, more and specific biochemical analyses are required to identify the pathophysiological role of eicosanoid.Abbreviations PG prostaglandin - Tx thromboxane - PGE-M 7-hydroxy-5,11-diketotetranorprostane-1,16-dioic acid - SRS-A slow reacting substance of anaphylaxis - NSAI drugs nonsteroidal anti-inflammatory drugs - PDA patent ductus arteriosus     

抗N-甲基-D-天冬氨酸受体脑炎

N-甲基-D-天冬氨酸(NMDA)受体是包含谷氨酸和甘氨酸结合位点的离子通道,在中枢神经系统的突触传递和突触可塑性调节中起重要作用.已证实的3种NMDA亚基,在体内有着不同的分布和功能.抗NMDA受体脑炎是近年才被确认的好发于年轻女性的可治疗的疾病,其临床特点为精神病性脑病、癫(癎)样发作以及躯干和面部的异常运动,特别是下颌关节肌张力异常.近年儿童抗NMDA受体脑炎有逐渐增多趋势.因此,增加对典型临床表现的认识,可提高对本病的早期识别并给予适当的治疗.     

5-HT3受体与肠易激综合征

5-羟色胺(5-HT)及其受体广泛分布于胃肠道.5-HT3受体属于配体门控阳离子通道家族.现已分离5-HT3A、5-HT3B、5-HT3D和5-HT3E5种受体亚基.5-HT3受体基因型与肠易激综合征发病机制紧密联系,5-HT转运体基因型多态性影响肠易激综合征-D患者对5-HT3受体调节剂治疗效果.阿洛司琼、雷莫司琼为新一代选择性5-HT3受体拮抗剂,具有调节肠道动力及内脏感觉的药理作用,是治疗腹泻型肠易激综合征的有效药物;雷莫司琼和5-HT3受体具有更强的亲和力、更慢的解离速度和更强的拮抗活性.     

5-HT3受体与肠易激综合征

5-羟色胺(5-HT)及其受体广泛分布于胃肠道.5-HT3受体属于配体门控阳离子通道家族.现已分离5-HT3A、5-HT3B、5-HT3D和5-HT3E5种受体亚基.5-HT3受体基因型与肠易激综合征发病机制紧密联系,5-HT转运体基因型多态性影响肠易激综合征-D患者对5-HT3受体调节剂治疗效果.阿洛司琼、雷莫司琼为新一代选择性5-HT3受体拮抗剂,具有调节肠道动力及内脏感觉的药理作用,是治疗腹泻型肠易激综合征的有效药物;雷莫司琼和5-HT3受体具有更强的亲和力、更慢的解离速度和更强的拮抗活性.     

5-HT3受体与肠易激综合征

5-羟色胺(5-HT)及其受体广泛分布于胃肠道.5-HT3受体属于配体门控阳离子通道家族.现已分离5-HT3A、5-HT3B、5-HT3D和5-HT3E5种受体亚基.5-HT3受体基因型与肠易激综合征发病机制紧密联系,5-HT转运体基因型多态性影响肠易激综合征-D患者对5-HT3受体调节剂治疗效果.阿洛司琼、雷莫司琼为新一代选择性5-HT3受体拮抗剂,具有调节肠道动力及内脏感觉的药理作用,是治疗腹泻型肠易激综合征的有效药物;雷莫司琼和5-HT3受体具有更强的亲和力、更慢的解离速度和更强的拮抗活性.     

Geschlechtsentwicklung zwischen Genen und Hormonen

Sex differences in males and females develop through the action of sex specific genes and hormones. Specific sex different genes are responsible for the development of the unspecific gonad into testes or ovaries. They are responsible for the secretion of sex hormones which regulate the differentiation of internal and external genitalia, pubertal development and fertility. Sex specific differences are also present in the brain, particularly in the hypothalamus and preoptic area. These morphologic differences are most likely responsible for the development of a sexual identity and a sex specific orientation. They regulate the characteristic behavioral patterns during mating and influence maternal or paternal behavior. Most morphologic and biochemical differences between males and females are still unknown, only a minor part can be clearly associated with specific genes. However, it is certain that the major part of sex specific behavior is genetically determined. To identify these and to differentiate them from socially-determined behavior further investigations are needed.     

Nutritional aspects of the short bowel syndrome

Adequate oral nutrition in patients with short bowel syndrome after operation is limited by the amount of intestine left after resection. The remnant small intestine has an important capacity to compensate for the loss of mucosal tissue and develops intestinal hyperplasia when stimulated by a variety of luminal and extraluminal factors such as nutrients, pancreatic biliary secretions, growth factors and hormones. In order to provide appropriate stimuli for the intestinal adaptation after resection, oral feeding is necessary as early as possible after operation. Among nutrients fat, especially LCT and free fatty acids, are the most stimulating nutrients besides proteins and carbohydrates. They increase pancreatic biliary secretions and the excretion of growth promoting hormones such as enteroglucagon. Because of gastric acid hypersecretion the administration of H2 receptor blocking agents (cimetidine) is recommended in these patients. As oral caloric intake is not sufficient in most patients with short bowel syndrome after operation total parenteral nutrition (TPN) or home-TPN has to be installed for longer periods to supplement the appropriate nutritional needs. Both early oral feeding together with TPN or home-TPN have increased considerably the survival rate of children with short bowel syndrome.