Growth-promoting Hormones Research Articles

Organ-specific expression of brassinosteroid-biosynthetic genes and distribution of endogenous brassinosteroids in Arabidopsis.

Brassinosteroids (BRs) are steroidal plant hormones that are essential for growth and development. There is only limited information on where BRs are synthesized and used. We studied the organ specificity of BR biosynthesis in Arabidopsis, using two different approaches: We analyzed the expression of BR-related genes using real-time quantitative reverse transcriptase-polymerase chain reaction, and analyzed endogenous BRs using gas chromatography-mass spectrometry. Before starting this study, we cloned the second BR-6-oxidase (BR6ox2) gene from Arabidopsis and found that the encoded enzyme has the same substrate specificity as the enzyme encoded by the previously isolated 6-oxidase gene (BR6ox1) of Arabidopsis. Endogenous BRs and the expression of BR-related genes were detected in all organs tested. The highest level of endogenous BRs and the highest expression of the BR6ox1, BR6ox2, and DWF4 genes were observed in apical shoots, which contain actively developing tissues. These genes are important in BR biosynthesis because they encode the rate-limiting or farthest downstream enzyme in the BR biosynthesis pathway. The second highest level of endogenous BRs and expression of BR6ox1 and DWF4 were observed in siliques, which contains actively developing embryos and seeds. These findings indicate that BRs are synthesized in all organs tested, but are most actively synthesized in young, actively developing organs. In contrast, synthesis was limited in mature organs. Our observations are consistent with the idea that BRs function as the growth-promoting hormone in plants.

Inhibitory mechanisms of kinetin, a plant growth-promoting hormone, in platelet aggregation

Kinetin has been shown to have anti-aging effects on several different systems including plants and human cells. The aim of this study was to examine the detailed inhibitory mechanisms of kinetin in platelet aggregation. In this study, kinetin concentration-dependently (50-150 μM) inhibited platelet aggregation in human platelets stimulated by agonists. Kinetin (70 and 150 μM) also concentration-dependently inhibited intracellular Ca2+ mobilization and phosphoinositide breakdown in platelets stimulated by collagen (1 μg/ml). Kinetin (70 and 150 μM) significantly inhibited thromboxane A2 formation stimulated by collagen (1 μg/ml) and arachidonic acid (60 μM) in human platelets. In addition, kinetin (70 and 150 μM) significantly increased the formation of cyclic AMP. Intracellular pH values were measured spectrofluorometrically using the fluorescent probe BCECF-AM in platelets. The thrombin-evoked increase in pHi was markedly inhibited in the presence of kinetin (70 and 150 μM). Rapid phosphorylation of a platelet protein of molecular weight (Mr) 47 000 (P47), a marker of protein kinase C activation, was triggered by collagen (1 μg/ml). This phosphorylation was inhibited by kinetin (70 and 150 μM). In conclusion, these results indicate that the anti-platelet activity of kinetin may be involved in the following pathways: kinetin's effects may initially be due to inhibition of the activation of phospholipase C and the Na+/H+ exchanger. This leads to lower intracellular Ca2+ mobilization, followed by inhibition of TxA2 formation and then increased cyclic AMP formation, followed by a further inhibition of the Na+/H+ exchanger, ultimately resulting in markedly decreased intracellular Ca2+ mobilization and phosphorylation of P47. These results suggest that kinetin has an effective anti-platelet effect and that it may be a potential therapeutic agent for arterial thrombosis.

Somatostatin analogs and radiopeptides in cancer therapy.

Since the discovery of somatostatin (sst) in 1973, numerous chemical and biological studies have been carried out to develop sst analogs with enhanced resistance to proteases and prolonged activity. Three highly potent sst analogs-octreotide, lanreotide, and vapreotide-are now available in the clinic, and demonstrate efficacy in the treatment of tumors of the pituitary and the gastroenteropancreatic tract. The most striking effect is the control of hormone hypersecretion associated with these tumors. Available data on growth suppression in patients indicate a limited antiproliferative action, tumor shrinkage is observed in 10-20% patients, and tumor stabilization in about half of the patients for duration of 8-16 months. Eventually, however, all patients escape from sst analog therapy with regard to both hormone hypersecretion and tumor growth, the only exception being observed in acromegalic patients who do not experience tachyphylaxis even after more than 10 years of daily octreotide injection. The mechanism underlying the escape phenomenon is not yet clarified. Regarding the molecular mechanisms involved in sst antineoplastic activity, both indirect and direct effects via specific somatostatin receptors (SSTRs) expressed in the target cells have be described. Direct action may result from blockade of mitogenic growth signal or induction of apoptosis following interaction with SSTRs. Indirect effects may be the result of reduced or inhibited secretion of growth-promoting hormones and growth factors that stimulate the growth of various types of cancer; also, inhibition of angiogenesis or influence on the immune system are important factors. Five SSTR subtypes have been identified so far, which are variably expressed in a variety of tumors such as gastroenteropancreatic (GEP) tumors, pituitary tumors, and carcinoid tumors. Although all five SSTR subtypes are linked to adenylate cyclase, they are now known to affect multiple other cellular signaling systems and hence they differentially participate in the regulation of the various cellular processes. The finding of several laboratories that SSTR-expressing tumors frequently contain two or more SSTR subtypes, and the recent discovery that SSTR subtypes might form homo/heterodimers to create a novel receptor with different functional characteristics, expand the array of selective SSTR activation pathways and subsequent intracellular signaling cascades. This may lead to improved clinical protocols that take into account possible synergistic interactions between the SSTR subtypes present on the same cancer cell. Radiolabeled sst analogs, such as [(111)In]-[diethylenetriamine pentaacetic acid (DTPA)-D-Phe(1)]-octreotide (OcreoScan), have proved to be very useful for tumor scintigraphy and internal radiotherapy of SSTR overexpressing tumors. The recent introduction of the metal chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) considerably improved the stability of the radioconjugates, making possible the incorporation of a variety of radionuclides, such as (90)Y for receptor-mediated radionuclide therapy or (68)Ga for positron emission tomography (PET). Another promising area is the development of sst conjugates incorporating cytotoxic anticancer drugs.

Growth hormone signalling and its regulation: preventing too much of a good thing.

Growth hormone (GH) is a major growth-promoting and metabolic regulatory hormone. Interaction of GH with its cell surface GH receptor (GHR), by virtue of receptor dimerization, causes activation of the GHR-associated cytoplasmic tyrosine kinase, JAK2. Several signalling pathways, including the STAT5, PI3 kinase and MAP kinase pathways, are thereby accessed, resulting in various biochemical and biological cellular signalling outcomes which are rapidly becoming deciphered. Various mechanisms probably exist to terminate, modulate and prevent GH signalling. Some of these mechanisms regulate receptor abundance and/or availability while others may alter the responsiveness of downstream signalling molecules to receptor engagement. In this review, recent insights into modulation of GH signalling are discussed. Special emphasis is placed on mechanisms of homologous and heterologous desensitization and on the likelihood that inducible GHR proteolysis, in addition to causing GH binding protein generation, may also serve as an important mechanism of heterologous GHR downregulation.

Induction of Atypical Ductal Hyperplasia in Mouse Mammary Gland Organ Culture

Induction of Atypical Ductal Hyperplasia in Mouse Mammary Gland Organ Culture

The growth hormone and insulin-like growth factor axis: its manipulation for the benefit of growth disorders in renal failure.

Renal failure is associated with dramatic changes in the growth hormone/insulin-like growth factor (GH/IGF) axis. In children, this results in growth retardation, which is treated with injections of recombinant human GH (rhGH). Given the many recent advances in the knowledge of the components of the GH/IGF axis, it is timely to review the role of GH in renal failure and to discuss likely new treatments for growth failure. Renal failure is not a state of GH deficiency but a state of GH and IGF resistance, making other approaches to manipulating the GH axis more logical than treatment with rhGH alone. Although in children rhGH is safe, in critically ill adults it can be lethal. As the mechanisms of these lethal actions of rhGH are unknown, caution is advised when using rhGH outside approved indications. In renal failure, an optimal balance between safety and efficacy for growth may be achieved with the use of the combination of rhGH and rhIGF-I, as animal studies have shown synergistic growth responses. However, inhibition of the GH axis, with the use of GH antagonists, is likely to be tested clinically given the beneficial effects of GH antagonists on renal function in animal models of renal disease. Manipulating IGF-I by either administering rhIGF-1 or its binding proteins or increasing IGF-I bioavailability with the use of IGF displacers could prove to be a safer and more effective alternative to the use of rhGH in renal failure. In the future, both rhGH and rhIGF-1 likely will be included in growth-promoting hormone cocktails tailored to correct specific growth disorders.

Peripheral Infusion of IGF-I Selectively Induces Neurogenesis in the Adult Rat Hippocampus

In several species, including humans, the dentate granule cell layer (GCL) of the hippocampus exhibits neurogenesis throughout adult life. The ability to regulate adult neurogenesis pharmacologically may be of therapeutic value as a mechanism for replacing lost neurons. Insulin-like growth factor-I (IGF-I) is a growth-promoting peptide hormone that has been shown to have neurotrophic properties. The relationship between IGF-I and adult hippocampal neurogenesis is to date unknown. The aim of this study was to investigate the effect of the peripheral administration of IGF-I on cellular proliferation in the dentate subgranular proliferative zone, which contains neuronal progenitor cells, and on the subsequent migration and differentiation of progenitor cells within the GCL. Using bromodeoxyuridine (BrdU) labeling, we found a significant increase of BrdU-immunoreactive progenitors in the GCL after 6 d of peripheral IGF-I administration. To determine the cell fate in progenitor progeny, we characterized the colocalization of BrdU-immunolabeled cells with cell-specific markers. In animals treated with IGF-I for 20 d, BrdU-positive cells increased significantly. Furthermore, the fraction of newly generated neurons in the GCL increased, as evaluated by the neuronal markers Calbindin D(28K), microtubule-associated protein-2, and NeuN. There was no difference in the fraction of newly generated astrocytes. Thus, our results show that peripheral infusion of IGF-I increases progenitor cell proliferation and selectively induces neurogenesis in the progeny of adult neural progenitor cells. This corresponds to a 78 +/- 17% (p < 0.001) increase in the number of new neurons in IGF-I-treated animals compared with controls.

Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human.

During the last decade, the GH axis has become the compelling focus of remarkably active and broad-ranging basic and clinical research. Molecular and genetic models, the discovery of human GHRH and its receptor, the cloning of the GHRP receptor, and the clinical availability of recombinant GH and IGF-I have allowed surprisingly rapid advances in our knowledge of the neuroregulation of the GH-IGF-I axis in many pathophysiological contexts. The complexity of the GHRH/somatostatin-GH-IGF-I axis thus commends itself to more formalized modeling (154, 155), since the multivalent feedback-control activities are difficult to assimilate fully on an intuitive scale. Understanding the dynamic neuroendocrine mechanisms that direct the pulsatile secretion of this fundamental growth-promoting and metabolic hormone remains a critical goal, the realization of which is challenged by the exponentially accumulating matrix of experimental and clinical data in this arena. To the above end, we review here the pathophysiology of the GHRH somatostatin-GH-IGF-I feedback axis consisting of corresponding key neurotransmitters, neuromodulators, and metabolic effectors, and their cloned receptors and signaling pathways. We propose that this system is best viewed as a multivalent feedback network that is exquisitely sensitive to an array of neuroregulators and environmental stressors and genetic restraints. Feedback and feedforward mechanisms acting within the intact somatotropic axis mediate homeostatic control throughout the human lifetime and are disrupted in disease. Novel effectors of the GH axis, such as GHRPs, also offer promise as investigative probes and possible therapeutic agents. Further understanding of the mechanisms of GH neuroregulation will likely allow development of progressively more specific molecular and clinical tools for the diagnosis and treatment of various conditions in which GH secretion is regulated abnormally. Thus, we predict that unexpected and enriching insights in the domain of the neuroendocrine pathophysiology of the GH axis are likely be achieved in the succeeding decades of basic and clinical research.

Blockade of growth hormone receptor shedding by a metalloprotease inhibitor.

GH, an important growth-promoting and metabolic hormone, exerts its biological effects by interacting with cell surface GH receptors (GHRs). The GHR is a single membrane-spanning protein that binds GH via its extracellular domain. The high affinity GH-binding protein (GHBP), which corresponds to a soluble form of the GHR extracellular domain, carries a substantial fraction of the GH in the circulation of various species and probably has a role in modulation of the hormone's bioavailability. Although in rodents, it is believed that the GHBP is largely derived by translation of an alternatively spliced GHR messenger RNA, in humans and rabbits, proteolytic cleavage of the membrane-anchored receptor releases the GHR extracellular domain, which is believed to thereby become the GHBP. In this study, we used human IM-9 lymphocytes and GHR antibodies to study this proteolytic shedding of the GHBP. As determined by immunoblotting with anti-GHR cytoplasmic domain serum, addition of phorbol 12-myristate 13-acetate (PMA; 1 microg/ml) to serum-starved cells led to rapid loss (roughly 60% decline after 1 h; t(1/2) = approximately 5 min) of mature GHRs (115-140 kDa) from either total cell or detergent-soluble extracts. Loss of full-length GHRs was accompanied by accumulation of four proteins (65-68 kDa), each reactive with the cytoplasmically directed antiserum. The pattern of appearance of these GHR ctyoplasmic domain proteins, the electrophoretic and immunological characteristics of which are similar to those of a recombinant rabbit GHR mutant that lacks the extracellular domain, was such that progressively faster migrating forms were evident between 5-60 min of PMA exposure. Treatment with N-ethylmaleimide (NEM; 5 mM), an agent known to cause GHBP shedding from IM-9 cells, promoted a similar rapid loss of full-length GHRs and an accumulation of GHR cytoplasmic domain remnant proteins. PMA-induced, but not NEM-induced, GHR proteolysis was blocked by the protein kinase C inhibitor, GF109203X. Both PMA- and NEM-induced receptor proteolysis were, however, inhibited by the metalloprotease inhibitor, Immunex Compound 3 (minimum effective concentration, 10 microM). Notably, PMA and NEM also promoted shedding of GHBP into the conditioned medium of the cells, as determined by a chromatographic [125I]human GH binding assay; this GHBP shedding was also inhibited by Immunex Compound 3. These results strongly implicate a member(s) of the metalloprotease family as a potential GHBP-generating enzyme.

Insulin-like growth factor I is suppressed in socially subordinate male baboons.

Insulin-like growth factor (IGF) I is a potent growth-promoting and anabolic hormone with major roles in cellular growth and differentiation, protein metabolism and muscle physiology, wound healing, erythropoiesis, and immune stimulation. Few, if any, studies have examined social or psychological factors that could give rise to individual differences in IGF-I levels. As part of a long-term psychoendocrine study of a population of male baboons living freely in a national reserve in East Africa, we examined the relationship between social rank and IGF-I concentrations. We observed that social subordinance was associated with a relative suppression of IGF-I concentrations; no rank-related differences in concentrations of IGF-II or IGF-binding protein were observed. Extensive psychoendocrine literature suggests that the individual differences in IGF-I profiles were a consequence, rather than a cause, of the rank difference. We were able to rule out a number of possible proximal explanations for the rank-IGF-I correlation: 1) the correlation was not a function of age (which involves both an adolescent spurt in IGF-I concentrations as well as a decline in concentrations in aged individuals); 2) the IGF-I suppression in subordinate individuals could not be explained by the basal hypercortisolism typical of such subordinate animals; and 3) neither differences in the quality or quantity of food consumed, in basal testosterone concentrations, nor in genetics could explain the rank difference. Although the mediating mechanisms responsible for this rank difference were not discernible in this study, the magnitude of difference in IGF-I levels among baboons of differing ranks might be of physiological significance.

Differential expression of a CAK (cdc2-activating kinase)-like protein kinase, cyclins and cdc2 genes from rice during the cell cycle and in response to gibberellin.

Progress through the eukaryotic cell cycle is regulated by cyclin-dependent cdc2 protein kinases. In rice (Oryza sativa L), two cdc2 protein kinases, cdc2Os-1 and cdc2Os-2, and two cyclins, cycOs1 and cycOs2, have been described. In this study, we report on the cell-cycle phase-specific expression of these genes. Using partially synchronized suspension cells from rice, we found that cdc2Os-1 was expressed constitutively throughout the cell cycle. The cdc2Os-2 transcript level was elevated in G1 and S phase. The cycOs1 and cycOs2 transcripts increased steadily through G2 and dropped off rapidly in mitosis as is typical for mitotic cyclins. We hypothesize that the cdc2Os-2 gene product acts in G1/S and that the growth-promoting hormone gibberellin (GA) that induces expression of cdc2Os-2, cycOs1 and cycOs2 in the intercalary meristem of deepwater rice internodes accelerates G1/S phase progression through increased expression of cdc2Os-2 and G2/M phase progression through increased expression of the mitotic cyclins cycOs1 and cycOs2. The R2 gene from rice has 55% sequence identity to the cdc2-activating kinase (CAK) family of protein kinases which have been shown to phosphorylate and thereby activate cdc2 protein kinases in animals and yeast. In partially synchronized suspension cells, R2 mRNA levels were elevated in G1 and S phase. In GA-treated rice internodes, R2 transcript levels were elevated in the meristem and part of the elongation zone. These results are consistent with a role for R2 in regulating G1/S phase progression.

A ribosomal 5S rRNA-binding protein gene from rice ( Oryza sativa L.) is regulated in a cell cycle phase-specific manner and in response to gibberellin

Summary Transcripts of a ribosomal 5S rRNA-binding protein from rice ( Oryza sativa L.), RL5, were shown to accumulate in internodes of deepwater rice after treatment with the growth-promoting hormone gibberellin (GA). Induction of RL5 expression by GA in the rice internode was limited to the intercalary meristem and to the lower half of the elongation zone. Expression of RL5 was induced in Gl phase of the cell cycle and reduced in abundance during S phase and again during mitosis. These results indicate that RL5 expression is highest in proliferating cells and is induced by mitotic stimulation. However, transcript levels are not consistently high in proliferating cells, but, instead, they are highly regulated during passage of cells through the different phases of the cell division cycle.

Inhibition of 5 alpha-reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids.

Isoflavonoids and lignans, constituents of many plant foods, have been proposed as protective agents in those populations with a low incidence of hormone-dependent cancers. They may act by their inhibition of the metabolism of growth-promoting steroid hormones. This report describes the inhibition of 5 alpha-reductase and 17 beta-hydroxysteroid dehydrogenase by six isoflavonoids and two lignans in human genital skin fibroblast monolayers and homogenates, and in benign prostatic hyperplasia tissue homogenates. In genital skin fibroblasts, genistein, biochanin A and equol were the most potent inhibitors of 5 alpha-reductase activity, each resulting in greater than 80% inhibition at a concentration of 100 microM. The IC50 values for genistein and a seven-compound mixture were approximately 35 microM and 20 microM (2.9 microM of each compound) respectively. Of the lignans, enterolactone was the most potent inhibitor. Inhibition by biochanin A was shown to be reversible. When genital skin fibroblast homogenates were used, biochanin A was found to inhibit 5 alpha-reductase isozymes 1 and 2 to differing extents (30% and 75% respectively). Genistein was shown to inhibit 5 alpha-reductase 2 in a non-competitive nature (Vmax and Km values without and with inhibitor were 30 and 20 pmol/mg protein per h and 177 and 170 nM respectively). All of the compounds tested inhibited 17 beta-hydroxysteroid dehydrogenase activity in genital skin fibroblast monolayers. When prostate tissue homogenates were used, the compounds tested were better inhibitors of 5 alpha-reductase 1 than 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Cancer from Beef: DES, Federal Food Regulation, and Consumer Confidence.

After World War II, agricultural college laboratories discovered in diethylstilbestrol (DES) a growth-promoting hormone of potentially wide commercial use in the cattle industry. In the post-war period of high prosperity and public confidence in science, government approval came quickly. Mass production began in 1954, and the promotional efforts of cattle-feed manufacturers soon convinced farmers of the drug's growth-enhancement - and profit-boosting - powers. Yet gradually, writes Alan Marcus, other scientists began to suspect links between DES-produced beef and cancer in humans. In this book, Marcus traces these developments, as DES emerged as a cause celebre - a source of expert factionalism and subject of various attempts to establish safe public policy. Marcus aims to show how DES figured in the enactment of three major pieces of federal regulatory legislation and how the DES controversy led to the establishment of new kinds of risk-assessment models in human health. Cancer from Beef uses the DES story to explore the intersection of institutional science, government rule-making and growing skepticism in popular attitudes toward both public protection and scientific authority. Marcus concludes that the DES story provides a case study in the attempt to control uncertainty in our lives when neither science nor government seem effective.

Tamoxifen is A Na+-Antagonistic Inhibitor of Na+/K+-Transporting ATPase from Tumour and Normal Cells

AbstractTamoxifen is the most widely used antihormonal agent for the treatment of estrogen receptor-positive breast cancer.1 Tamoxifen controls breast cancer cell replication by blocking the binding of estrogen to the estrogen receptor and preventing estrogen-stimulated growth.2 It displaces the growth-promoting natural hormone estradiol-17β from its protein receptor and, consequently, its principal mode of action has been thought to be as an antiestrogen.2

Tissue distribution and ontogeny of growth hormone receptor messenger ribonucleic acid and ligand binding to hepatic tissue in the midgestation sheep fetus.

While circulating GH concentrations are high in fetal life, skeletal growth is only slightly reduced by GH deficiency in utero. This has been explained by the relatively low binding of GH to fetal hepatic tissue, suggesting a lack of GH receptors (GHR). The GHR also recognizes ovine placental lactogen (oPL), which may have a specific role either as a fetal growth-promoting hormone or in regulating fetal metabolism. We investigated GHR expression and membrane binding of ovine (o) GH and oPL in various ovine fetal tissues and in maternal liver at different gestational stages. Singleton-bearing ewes at 51, 95, and 120 days gestation were killed. Liver, muscle, kidney, and brain samples were taken from the fetuses as well as placentas and livers from the ewes (n = 3/gestational age). GHR mRNA measured by Northern blot analysis was expressed at high levels in maternal liver at all gestational stages. A major band was observed at 4.4 kilobases (kb), and three minor bands were observed at 2.5, 1.7, and 8.1 kb. In fetal and placental tissue, only the 4.4-kb band was detected. This was present as early as day 51 of gestation in liver, kidney, lung, heart, and placenta and increased slightly with advancing gestation. On day 51, the expression of GHR mRNA in muscle was negligible, but by day 95, muscle expressed higher concentrations than fetal liver. Placental samples showed only a slight signal, with no change over the gestational range studied. In situ hybridization revealed the placental mRNA to be primarily associated with the decidua. Hepatic tissue showed specific binding to [125I]oGH and [125I]oPL from 51 days gestation. [125I]oPL showed a higher [51 days, 17.9 +/- 1.9% (mean +/- SEM); 95 days, 11.5 +/- 1.6%; 120 days, 16.3 +/- 0.9%] specific binding to the liver membranes than [125I]oGH (51 days, 2.1 +/- 0.7%; 95 days, 2.6 +/- 0.3%; 120 days, 3.5 +/- 0.4%). We conclude that oGHR are present as early as day 51 of gestation in various tissues, including liver. The message appears later in skeletal muscle than in liver. As the GH receptor binds oPL with higher potency than oGH, the parallel ontogenic changes in [125]oGH and [125]oPL binding in the liver do not support the presence of a PL receptor under independent developmental regulation.

Signals for Cardiac Muscle Hypertrophy in Hypertension

Hypertension is associated with a rise in arterial pressure and a compensatory increase in cardiac mass, which if not treated effectively, progresses to decompensated congestive heart failure. This decompensation of an initially compensatory hypertrophy has intensified interest in the factors that initiate and maintain the development of cardiac hypertrophy. The potential signals that induce the development of cardiac hypertrophy are grouped as hemodynamic, growth-promoting hormonal, vasoconstriction-promoting hormonal, and genetic factors. Growth-promoting hormones such as insulin and thyroxine appear to play a permissive, but essential, role in the development and maintenance of cardiac hypertrophy. However, changes in cardiac load, both above and below normal, result in parallel changes in cardiac mass, which will return to normal when a normal load is restored. This adaptive response of the myocardium in direct response to elevated and depressed loads demonstrates that cardiac structure, composition, and function are not fixed postneonatal cardiac properties, but instead are regulated dynamically by the cardiocyte loading environment. This adaptive response is subject to modulation by vasoconstriction-promoting hormones and genetic factors. The current thrust in this research area is to elucidate the cellular signals that transduce the physical stimulus for hypertrophy into biochemical events underlying hypertrophic cardiac growth. To remove complex systemic interactions in vivo from the experimental paradigm, several in vitro models have been used to examine three general, but distinct, cellular pathways involving protein kinase C activation, cyclic AMP formation, and increased ion fluxes. Each pathway demonstrated a stimulatory effect on general protein synthesis, which is necessary for growth in all cells.(ABSTRACT TRUNCATED AT 250 WORDS)

The Chemical Jungle: Today's Beef Industry

In the absence of effective federal regulation, the meat industry uses hundreds of animal feed additives, including antibiotics, tranquilizers, pesticides, animal drugs, artificial flavors, industrial wastes, and growth-promoting hormones, with little or no concern about the carcinogenic and other toxic effects of dietary residues of these additives. Illustratively, after decades of misleading assurances of the safety of diethylstilbestrol (DES) and its use as a growth-promoting animal-feed additive, the United States finally banned its use in 1979 some 40 years after it was first shown to be carcinogenic. The meat industry then promptly switched to other carcinogenic additives, particularly the natural sex hormones estradiol, progesterone, and testosterone, which are implanted in the ears of more than 90 percent of commercially raised feedlot cattle. Unlike the synthetic DES, residues of which can be monitored and use of which was conditional on a seven-day preslaughter withdrawal period, residues of natural hormones are not detectable, since they cannot be practically differentiated from the same hormones produced by the body. The relationship between recently increasing cancer rates and the lifetime exposure of the U.S. population to dietary residues of these and other unlabeled carcinogenic feed additives is a matter of critical public health concern.

Fruiting of cotton IV. Nitrogen, abscisic acid, indole-3-acetic acid, and cutout

Decreases in growth, flowering rate, and fruit (boll) retention of cotton ( Gossypium hirsutum L.) characterize cutout, a hiatus in fruiting. Nitrogen deficiency hastens cutout, and has been reported to cause an increase in the concentration of abscisic acid (ABA), a growth-inhibiting hormone. A field experiment was conducted with ‘Deltapine 61’ cotton to determine possible effects of N deficit on the concentrations of ABA and the growth-promoting hormone, indole-3-acetic acid (IAA), in cotton fruiting branches in relation to their growth, flowering rate, and boll retention. Three harvests were made during the fruiting cycle in 1987 to determine if the ABA concentration of fruiting branches increased or IAA concentration decreased as growth decreased during the season. Three harvests were made the next season (1988) to determine possible changes in concentrations of ABA and IAA in flower buds and flowers. Fruiting branches were always shorter on low-N than on high-N plants, and fruiting branches that developed late in the season were much shorter than those that developed early. The ABA concentrations in fruiting branches decreased after 9 July and ABA concentrations were always lower in fruiting branches of low-N than high-N plants. Therefore, the results do not support the hypothesis that ABA accumulates in N-deficient cotton fruiting branches and inhibits their growth. Decreasing concentrations of IAA, however, could have been a cause of decreased growth of fruiting branches. The IAA content of fruiting branches decreased during the fruiting cycle, and was lower in low-N than in high-N plants except in the last harvest. ABA increased and IAA decreased in 3-day-old bolls as boll retention decreased. The concentrations of ABA in flower buds and flowers did not increase during the season and were not affected by N deficiency. Likewise, the concentrations of IAA in flower buds and flowers were not affected by N. The concentration of IAA in flower buds decreased during the season, however. In general, the results support the hypothesis that the IAA of cotton fruiting branches is affected by N deficit, decreases during the fruiting cycle, and may be a factor in the decreases in growth, flowering, and boll retention commonly referred to as cutout.

Selection experiments for body composition in mice and rats: A review

Selection studies for body composition traits that used mice and rats as a model for livestock have been reviewed. Average realized heritability is higher for fat traits (0.49) than for lean traits (0.37), but there is considerable overlap. Selection for lean weight traits produced positive realized genetic correlations in growth, feed intake, gross feed efficiency and lean body mass, but body fat and protein percentages were not modified significantly at age of selection. Selection for fat percentage caused positive genetic correlations in growth, feed intake, feed efficiency and body fat, a negative response in body protein percentage and no response in lean body mass. An inexpensive and non-invasive method of measuring body composition is needed to improve the technical efficiency of selection. Future research should compare genetic variation in body composition at different ages. Desired gains and restricted selection index methods should be applied to modify body composition and growth. Hormones known to affect body composition and growth may be considered as additional selection criteria. Use of transgenic animals carrying genes coding for growth-promoting hormones, combined with artificial selection, offer additional strategies for changing body composition.