Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth

To examine the relationship between growth hormone (GH) and insulin-like growth factor 1 (IGF1) in controlling postnatal growth, we performed a comparative analysis of dwarfing phenotypes manifested in mouse mutants lacking GH receptor, IGF1, or both. This genetic study has provided conclusive evidence demonstrating that GH and IGF1 promote postnatal growth by both independent and common functions, as the growth retardation of double Ghr/Igf1 nullizygotes is more severe than that observed with either class of single mutant. In fact, the body weight of these double-mutant mice is only approximately 17% of normal and, in absolute magnitude ( approximately 5 g), only twice that of the smallest known mammal. Thus, the growth control pathway in which the components of the GH/IGF1 signaling systems participate constitutes the major determinant of body size. To complement this conclusion mainly based on extensive growth curve analyses, we also present details concerning the involvement of the GH/IGF1 axis in linear growth derived by a developmental study of long bone ossification in the mutants.     

Actions and interactions of growth hormone and insulin-like growth factor-II: body and organ growth of transgenic mice

To characterize long-term actions and interactions of growth hormone (GH) and insulin-like growth factor-II (IGF-II) on postnatal body and organ growth, hemizygous phosphoenolpyruvate carboxykinase (PEPCK)-human IGF-II transgenic mice were crossed with hemizygous PEPCK-bovine GH transgenic mice. The latter are characterized by two-fold increased serum levels of IGF-I and exhibit markedly increased body, skeletal and organ growth. Four different genetic groups were obtained: mice harbouring the IGF-II transgene (I), the bGH transgene (B), or both transgenes (IB), and non- transgenic controls (C). These groups of mice have previously been studied for circulating IGF-I levels (Wolf et al., 1995a), whereas the present study deals with body and organ growth. Growth curves (week 3 to 12) were estimated by regression with linear and quadratic components of age on body weight and exhibited significantly (p < 0.001) greater linear coefficients in B and IB than in I and C mice. The linear coefficients of male I and C mice were significantly (p < 0.001) greater than those of their female counterparts, whereas this sex-related difference was absent in the bGH transgenic groups. The weights of internal organs as well as the weights of abdominal fat, skin and carcass were recorded from 3.5- to 8- month-old mice. In addition, organ weight-to-body weight-ratios (relative organ weights) were calculated. Except for the weight of abdominal fat, absolute organ weights were as a rule significantly greater in B and IB than in I and C mice. IGF-II overproduction as a tendency increased the weights of kidneys, adrenal glands, pancreas and uterus both in the absence and presence of the bGH transgene. Analysis of relative organ weights demonstrated significant (p < 0.05) effects of elevated IGF- II on the relative growth of kidneys (males and females) and adrenal glands (females), confirming our previous report on organ growth of PEPCK-IGF-II transgenic mice. In females, IGF-II and GH overproduction were additive in stimulating the growth of spleen and uterus, providing evidence for tissue-specific postnatal growth promoting effects by IGF-II in the presence of elevated IGF-I     

The growth of growth

Over a 40-year period, 1940 through the present, human growth research has increased from a minimal to a major part of physical anthropology. Such research, originally conducted at the major American growth centers, has become more diverse and more specialized, extending to National Probability Samplings, nutritional surveys, studies of twins, investigations restricted to the craniofacial complex, and studies of the growth and development of various primate species. Besides extending knowledge of growth and development in general and control mechanisms in particular, there has been major feedback into physical anthropology affording far greater understanding of human variability, of taxonomic differences, and of changes previously believed to be phylogenetic in nature. To the larger extent, all physical anthropologists have some degree of growth awareness.     

Transforming growth factors and control of neoplastic cell growth

Transforming growth factors (TGFs) are peptides that affect the growth and phenotype of cultured cells and bring about in nonmalignant fibroblastic cells phenotypic properties that resemble those of malignant cells. Two types of TGFs have been well characterized. One of these, TGF alpha, is related to epidermal growth factor (EGF) and binds to the EGF receptor, whereas the other, TGF beta, is not structurally or functionally related to TGF alpha or EGF and mediates its effects via distinct receptors. TGF beta is produced by a variety of normal and malignant cells. Depending upon the assay system employed, TGF beta has both growth-inhibitory and growth-stimulating properties. Many of the mitogenic effects of TGF beta are probably an indirect result of the activation of certain growth factor genes in the target cell. The ubiquitous nature of the TGF beta receptor and the production of TGF beta in a latent form by most cultured cells suggests that the differing cellular responses to TGF beta are regulated either by events involved in the activation of the factor or by postreceptor mechanisms. The combined effects of TGF beta with other growth factors or inhibitors evidently play a central role in the control of normal and malignant cellular growth as well as in cell differentiation and morphogenesis. Since transforming growth factor as a concept has partially proven misleading and insufficient, there is a need to find a new nomenclature for these regulators of cellular growth and differentiation.     

Novel polymorphisms of goat growth hormone and growth hormone receptor genes and their effects on growth traits

In this study, the polymorphisms of growth hormone (GH) gene 5' promoter region and intron 8, exons 4 and 10 of growth hormone receptor (GHR) gene were analyzed in Xinong Saanen goats (SG) and Boer goats (BG). Two alleles (A and B) and three genotypes (AA, AB and BB) were detected at P1 locus of GH gene, and two alleles (G and T) and two genotypes (GG and GT) were detected at P4 locus of GHR gene by PCR-SSCP analysis. In addition, two single nucleotide polymorphisms (SNPs)-A73C (P1 locus) and G114T (P4 locus), were identified by DNA sequencing. The frequencies of alleles A and B in the two goat breeds were 0.61-0.62, and 0.39-0.38, respectively, and the frequencies of alleles G and T in the two goat breeds were 0.82-0.86, and 0.18-0.14, respectively. The SNP loci were in Hardy-Weinberg disequilibrium in both goat breeds (P<0.05). Polymorphisms of GH and GHR genes were shown to be associated with growth traits in BG breed. AA and GG genotypes were associated with superior growth traits in 1-, 2- and 3-month old individuals. Hence, AA and GG genotypes are suggested to be a molecular marker for superior growth traits in BG breed.     

Relationship of growth hormone and insulin-like growth factor-1 genotypes with growth and carcass traits in swine

The contribution of chromosomal regions linked to growth hormone (GH) and insulin-like growth factor-1 (IGF-1) loci to variation in preweaning average daily gain, postweaning average daily gain (ADG), 10th rib backfat, loin-eye area and muscle pH were evaluated. Offspring of four purebred sires (A–D; n = 150, 195, 148 and 136, respectively) and two crossbred sires (E and F; n = 157 and 145, respectively) were genotyped initially with GH and IGF-1 markers. When results of single marker analysis suggested possible linkage with a quantitative trait locus (QTL), additional flanking markers were typed for the family and interval mapping was performed. Growth hormone genotype was not associated with the traits evaluated in the study. Evidence suggestive of linkage was found for IGF-1 genotype and ADG in one sire family (lod = 2·3) where differences were 0.032 ± 0·01 kg/day for alternative sire alleles. Evidence for a putative ADG QTL was greatest in the interval between IGF-1 and Sw1071. A similar genomic region has been associated with growth variation in mice; however, QTL mapping precision in the current study is insufficient to establish similarity.     

多肽类生长因子对前列腺生长和功能的调节

多肽类生长因子是前列腺生长及功能的正向及负向调节因子,这些生长因子中,表皮生长因子和转化生长因子α,成纤维生长因子家族,胰岛素样生长因子家族是主要的促生长因子,而转化生长因子β是唯一的负向生长调节因子,前列腺病理情况下,这些生长因子的表达和分泌方式发生改变。     

Promotion of asparagus shoot and root growth by growth retardants

Plantlets regenerated from shoot-tip culture of Asparagus officinalis L. possessed weak shoots and roots. Various combinations of auxins and cytokinins did not improve the plantlets. Incorporation of a number of growth retardants, viz. ancymidol, B-995, phosfon, Amo 1618, cycocel and paclobutrazol, promoted growth of stronger shoots and roots. The effectiveness of the growth retardants varied, with ancymidol being most effective and cycocel least effective.The response to ancymidol was prevented by exogenous GA₃ and GA_4/7. GA_1/3 and GA_4/7-like activities were detected in asparagus shoot-tip culture and these activities were reduced by the presence of the growth retardants ancymidol, Amo-1618, and cycocel.     

Cranial growth and growth dimorphism in Ateles geoffroyi

With the exception of the work of Schultz (1960), cranial growth in Ateles is not well documented. This paper describes the results of a detailed quantitative study of cranial ontogeny in male and female Ateles geoffroyi. Using Euclidean Distance Matrix Analysis (EDMA), local areas of form change due to growth within spider monkey crania are identified. We found substantial change local to the zygomatic region in the face, identified mediolaterally directed changes in the palate, detected relatively larger amounts of change local to the anterior neurocranium compared to the posterior neurocranium, and demonstrate a greater amount of basicranial growth along a mediolateral axis than previously reported. Cranial sexual dimorphism is also examined. A. geoffroyi is noted for being monomorphic, and we found a general similarity between male and female cranial forms at all developmental ages. However, differences in overall cranial size between the sexes were found in the oldest subadult age group but not between male and female adults. This difference suggests that A. geoffroyi females attain their adult cranial form slightly before males and implies a pattern of earlier onset of female maturity relative to males. © 1993 Wiley-Liss, Inc.     

Polypeptide growth factors in embryogenesis and tumor growth

Polypeptide growth factors, which belong to different families (epidermal growth factors, insulin-like growth factors, fibroblast growth factors, transforming growth factors-beta, and some others), were characterized regarding their specific role in embryogenesis and tumor growth. Differences and parallels of the functioning of growth factors in these processes have been noted. Potential significance of the described characteristics of growth factors for directed modulation of embryogenesis and tumor growth is discussed.     

Osteoporosis and the growth hormone-insulin-like growth factor axis

Osteoporosis is the result of an imbalance between bone resorption and bone formation. Currently, mainly drugs that inhibit bone resorption are available for the treatment of osteoporosis. A new approach in the treatment of osteoporosis is the use of anabolic agents that increase bone turnover, both bone formation and resorption. Growth hormone (GH) and insulin-like growth factors (IGFs) are essential in the development and growth of the skeleton and for the maintenance of bone mass and density. We will review the evidence of GH and IGF-I in the pathophysiology and treatment of osteoporosis.     

Structural-proliferative units and organ growth: effects of insulin-like growth factor 2 on the growth of colon and skin

Many epithelial renewal tissues in vertebrates are organised into structural-proliferative units. We have examined the effect of IGF2 dose on the structure of structural-proliferative units in skin and colon. The mouse strains used were the Igf2 knockout, wild type and K:Igf2, a transgenic in which Igf2 is overexpressed under control of a keratin promoter. For both skin and colon, the histological organisation of structural-proliferative units was unaltered with increasing IGF2 dose, although there was a higher fraction of dividing cells in the proliferative compartment. In the colon an increase in IGF2 dose increases the overall area of the epithelium. This is due to an increase in the number of crypts with no change of cell size or of crypt area. Growth stimulation appears to be due to a reduction in the duration of crypt fission. The conclusion is that the IGF2 pathway can stimulate the multiplication of colonic crypts independently of stimulating increased cell proliferation. The results for the skin are consistent with this. An increase of IGF2 dose increases the proportion of dividing cells in the basal layer, the thickness of the epidermis and the total area of the epidermis. By comparison with Drosophila, these results show no effects on cell size, but do show the possibility of inducing disproportionate growth. These differences may represent properties of the SPU organisation that is characteristic of vertebrate tissues.     

Epidermal growth factor and transforming growth factor-alpha induce differential processing of the epidermal growth factor receptor

The capacity of epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) to induce internalization and degradation of the EGF receptor was compared in NIH-3T3 cells expressing the human EGF receptor. This study was initiated following the observation that TGF-alpha was much less efficient relative to EGF in generating a Mr = 125,000 amino-terminally truncated degradation product from the mature EGF receptor (EGF-dependent generation of this degradation product is described in S.J. Decker, J. Biol. Chem., 264:17641-17644). Pulse-chase experiments revealed that EGF generally stimulated EGF receptor degradation to a greater extent than TGF-alpha. Both ligands induced EGF receptor internalization to similar degrees. However, recovery of [125I]-EGF binding following incubation with EGF or TGF-alpha was much faster for TGF-alpha treated cells. Recovery of [125I]-EGF binding after TGF-alpha treatment did not appear to require protein synthesis. Tyrosine phosphorylation of EGF receptor from cells treated with TGF-alpha decreased more rapidly following removal of TGF-alpha compared to cells treated similarly with EGF. These data suggest that EGF routes the EGF receptor directly to a degradative pathway, whereas TGF-alpha allows receptor recycling prior to degradation, and that tyrosine phosphorylation could play a role in this differential receptor processing.