Somatostatin inhibits growth of rainbow trout

Implantation of rainbow trout Oncorhynchus mykiss with somatostatin-14 (SS-14) for 20 days resulted in reduced food conversion as well as significant growth retardation compared to controls. Relative growth as mass was reduced by 20%, whereas relative growth by length was reduced by 45%. A single intraperitoneal injection of SS-14 reduced plasma levels of growth hormone (GH), insulin-like growth factor-1 (IGF-I) and insulin. SS-14 injection also reduced [³⁵S]-sulphate incorporation into gill cartilage compared to saline-injected fish. In addition, in vitro incubation of gill cartilage with SS-14 reduced [³⁵S]-sulphate incorporation in a doserelated manner. These results indicate that SS-14 inhibits growth of rainbow trout and suggests that SS-14, in addition to influencing GH, may play an extra-pituitary role in the modulation of the GH-IGF-I axis.     

Homologous growth hormone (GH) binding in gilthead sea bream (Sparus aurata). Effect of fasting and refeeding on hepatic GH-binding and plasma somatomedin-like immunoreactivity

Specific binding of gilthead sea bream growth hormone (sbGH) to liver membrane preparations was a time and temperature dependent process, and was saturable by increasing amounts of membrane proteins. Scatchard analysis evidenced a single class of high-affinity and lowcapacity binding sites. Ovine prolactin, recombinant tilapia prolactin, carp gonadotropin and chinook salmon gonadotropin did not compete for the¹²⁵I-sbGH binding sites, while recombinant trout GH, bovine GH and human GH displaced iodinated sbGH in a dose dependent-manner. IGF-I-like immunoreactivity was detected after acidification of plasma and removal of IGF-I binding activity. A parallel displacement to the rhIGF-1 standard was observed with extracted plasma samples. Free and total hepatic GH-binding decreased during long-term starvation (3–9 weeks), returning to control values during the refeeding period. Plasma IGF-I-like immunoreactivity showed a similar trend. To our knowledge, this is the first report that indicates a coordinated regulation of GH-binding and plasma somatomedin-like activity in a typical marine fish.     

Glucose regulates ghrelin, neuropeptide Y, and the GH/IGF-I axis in the tilapia, Oreochromis mossambicus

In general, a fish's ability to clear glucose is sluggish in relation to mammals, which has lead to the idea that fish are glucose intolerant. It has been reported that circulating glucose levels do fluctuate in response to environmental challenges. Recent reports suggest that glucose may function as a metabolic signal regulating ‘glucosensors’ in the brain in fish, as has been reported in mammals. The current study was designed to investigate the effect of glucose on ghrelin and neuropeptide Y (NPY) signaling in the brain, and on the growth hormone/insulin-like growth factor-I (GH/IGF-I) in the tilapia, Oreochromis mossambicus. Glucose treatment significantly increased plasma and stomach mRNA levels of ghrelin. In the brain, mRNA levels of the ghrelin receptor (GRLN-R) were significantly reduced, whereas NPY mRNA levels were significantly elevated; suggesting that NPY containing neurons may be a “glucosensor” as reported in mammals. Glucose treatment resulted in changes in the GH/IGF-I axis. Liver mRNA levels of both GH receptors (GHR1 and GHR2) were significantly elevated, whereas liver IGF-I mRNA were unaltered by glucose treatment. No change in plasma or pituitary mRNA levels of GH was observed. Glucose significantly reduced plasma IGF-I levels. These data show that glucose regulates endocrine factors involved in appetite, growth, and possibly energy homeostasis, and suggests that glucose may be acting as a signal of metabolic status in fish.     

Distribution and regulation of rat insulin-like growth factor I messenger ribonucleic acids encoding alternative carboxyterminal E-peptides: evidence for differential processing and regulation in liver

Alternative splicing of insulin-like growth factor I (IGF-I)/somatomedin C mRNAs generates two IGF-I mRNAs coding for IGF-I peptides with different sequences in the E domain of the IGF-I prohormone. These two mRNAs encode alternative E peptides due to the presence (IGF-Ib) or absence (IGF-Ia) of a 52-base insert in the region coding for the E domain. We have used a solution hybridization/RNase protection assay to determine the tissue distribution and regulation by GH of the expression of these alternative IGF-I mRNAs. IGF-Ib mRNAs are present in low abundance (representing approximately 2.5% of the total IGF-I mRNA) in heart, lung, muscle, testes, stomach, kidney, and brain, but represent approximately 13% of the IGF-I mRNA in liver. GH treatment of hypophysectomized rats increased steady-state IGF-I mRNA levels in liver, kidney, lung, and heart. In kidney, lung, and heart, IGF-Ia and IGF-Ib mRNA levels were coordinately regulated by GH, but, in liver, the fold increase in IGF-Ib mRNA levels was approximately three times greater than the fold increase in IGF-Ia mRNA levels. These data suggest that the processing of IGF-I mRNA in liver is different than in nonhepatic tissues. These results also further elucidate the organization of the rat IGF-I gene as well as the generation of multiple IGF-I mRNAs by alternative splicing.     

Effect of recombinant growth hormone on expression of growth hormone receptor, insulin-like growth factor mRNA and serum level of leptin in growing pigs

Growth hormone (GH) plays an important role in regulation of animal growth, metabolism and lactation[1]. Numerous studies have shown that exogenous somatotropin (ST) can increase average daily weight gain, improve feed efficiency, stimulate protein deposition and muscle growth and decrease lipid accretion rate[1]. The original somatomedin hypothesis suggested that the effect of GH on postnatal growth was mediated by insulin-like growth hormone factor 1 (IGF-I) which was thought to be deriv…     

Hypothalamic-pituitary somatotropic function in prepubertal hypothyroid rats: effect of growth hormone replacement therapy.

The effect of thyroid hormone deficiency and growth hormone (GH) treatment on hypothalamic GH-releasing hormone (GHRH)/somatostatin (SS) concentrations, GHRH/SS mRNA levels, and plasma GH and somatomedin-C (IGF-I) concentrations were studied in 28- and 35-day-old rats made hypothyroid by giving dams propylthiouracil in the drinking water since the day of parturition. Hypothyroid rats, at both 28 and 35 days of life, had decreased hypothalamic GHRH content and increased GHRH mRNA levels, unaltered SS content and SS mRNA levels, and reduced plasma GH and IGF-I concentrations. Treatment of hypothyroid rats with GH for 14 days completely restored hypothalamic GHRH content and reversed the increase in GHRH mRNA, but did not alter plasma IGF-I concentrations. These data indicate that, in hypothyroid rats, the changes in hypothalamic GHRH content and gene expression are due to the GH deficiency ensuing from the hypothyroid state. Failure of the GH treatment to increase plasma IGF-I indicates that the feedback regulation on GHRH neurons is operated by circulating GH and/or perhaps tissue but not plasma IGF-I concentrations. Presence of low plasma IGF-I concentrations would be directly related to thyroid hormone deficiency.     

Experimental arthritis inhibits the insulin-like growth factor-I axis and induces muscle wasting through cyclooxygenase-2 activation

Chronic arthritis induces cachexia associated with an inhibition of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) system and an activation of the E3 ubiquitin-ligating enzymes muscle atrophy F-box (MAFbx) and muscle Ring finger 1 (MuRF1) in the skeletal muscle. The aim of this work was to study the role of cyclooxygenase (COX)-2 in chronic arthritis-induced cachexia. Arthritis was induced in rats by Freund's adjuvant injection, and the effects of two COX inhibitors (indomethacin, a nonspecific inhibitor, and meloxicam, a selective COX-2 inhibitor on pituitary GH and on liver and serum IGF-I levels) were tested. Arthritis decreased body weight gain and GH and liver IGF-I gene expression. In the arthritic rats, both inhibitors, indomethacin and meloxicam, prevented the inhibitory effect of arthritis on body weight gain. Indomethacin and meloxicam administration to arthritic rats increased pituitary GH and liver IGF-I mRNA as well as serum levels of IGF-I. These data suggest that induction of COX-2 during chronic inflammation is involved in the inhibition of the GH-IGF-I axis and in the body weight loss. In the gastrocnemius muscle, arthritis increased the gene expression of tumor necrosis factor (TNF)-alpha, the E3 ubiquitin-ligating enzymes MAFbx and MuRF1, as well as of IGF-I and IGF-binding protein-5 (IGFBP-5). Inhibition of COX-2 by meloxicam administration increased gastrocnemius weight and decreased MAFbx, MuRF1, TNF-alpha, and IGFBP-5 gene expression. In summary, our data indicate that chronic arthritis-induced cachexia and muscle wasting are mediated by the COX-2 pathway resulting in a decreased GH-IGF-I secretion and increased expression of MAFbx and MuRF1 mRNA.     

Effects of fasting on growth hormone/insulin-like growth factor I axis in the tilapia,Oreochromis mossambicus

Effects of fasting on the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis were examined in the tilapia (Oreochromis mossambicus) acclimated to fresh water. Fasting for 2 weeks resulted in significant reductions in body weight, specific growth rate and hepatosomatic index in both males and females. Significant reductions in specific growth rates were observed after 1 and 2 weeks in both sexes, although the decrease in body weight was not significant in the female. A significant reduction was also seen in the condition factor of females after 2 weeks. No change was seen in the gonadosomatic index in either sex. Two weeks of fasting also produced a significant reduction in plasma IGF-I but not in plasma GH, prolactin (PRL(188)) or cortisol. Significant reductions in the hepatic IGF-I mRNA were seen in both sexes. On the other hand, a significant increase was observed in cortisol receptor mRNA in the female liver. Plasma IGF-I levels were correlated significantly with specific growth rate, condition factor and hepatosomatic index, indicating that plasma IGF-I is a good indicator of growth in the tilapia. No change was seen in plasma glucose or osmolality after 2 weeks of fasting. During fasting, tilapia appears to convert metabolic energy from growth to basal metabolism including maintenance of ion and water balance.     

Plasticity of smolting in spring chinook salmon: relation to growth and insulin-like growth factor-I

In two year classes of Willamette River spring chinook salmon, reared at the Willamette Hatchery, and two groups of Yakima River spring chinook salmon, one sampled from the Yakima River and the other reared in a hatchery, fish which had relatively high growth rates in the summer–autumn period smolted in the autumn as measured by increases in gill Na⁺ K⁺ AT Pase activity. In contrast, groups with relatively low growth rate did not smolt in the autumn. Plasma levels of insulin-like growth factor-I (IGF-I) showed discrete differences between groups, with high levels associated with increased gill Na⁺ K⁺ AT Pase activities. These results demonstrate that smolting is plastic in spring chinook salmon, occurring in the autumn or the spring. In addition, smolting appeared to be related to growth rate; however, the relationships shown were correlational and causal mechanisms were not elucidated. Yet, the results do indicate a relationship between growth, an endocrine growth factor and smolting, suggesting a mechanistic link between developmental plasticity and the environment mediated by the endocrine system.     

Effect of recombinant growth hormone on expression of growth hormone receptor,insulin-like growth factor mRNA and serum level of leptin in growing pigs

Sixteen Large White × Landrace castrated male pigs were allotted into treatment and control group. The treatment group was injected intramuscularly with recombinant porcine growth hormone (rpGH, 4 mg d⁻¹) and the control group with vehicle for 28 days. Animals were slaughtered 4 h after final injection for liver, longissimus dorsi (LD) muscle and blood sampling. Serum concentration of insulin-like growth factor 1 (IGF-I) and leptin were determined by RIA. The total RNA was extracted from tissues to measure the abundance of growth hormone receptor (GHR), IGF-I mRNA by RT-PCR with 18S rRNA internal standard. Results showed that rpGH enhanced the average daily weight gain by 26.1% (P < 0.05), the serum IGF-I concentration by 70.94% (P < 0.01), decreased serum leptin by 34.8% (P < 0.01). The relative abundance of GHR and IGF-I mRNA in liver were increased by 24.45% (P < 0.05) and 45.30% (P < 0.01), respectively, but no difference of GHR (P > 0.05) and IGF-I mRNA (P > 0.05) in LD between GH treated and control group was found. These results suggest that rpGH can up-regulate hepatic GHR and IGF-I gene expression and improve animal growth. However the effect of rpGH on GHR and IGF-I gene expression are tissue-specific.     

Influences of photoperiod and alternate days of feeding on plasma growth hormone and thyroid hormone levels in juvenile rainbow trout

The diurnal patterns of plasma growth hormone (GH), thyroid hormone and cortisol concentrations in rainbow trout Oncorhynchus mykiss held under three photoperiod (L : D) regimes (6 : 18, 12 : 12 and 18 : 6), and fed either daily (DF) or on alternate days (ADF) with 2·0% body mass per day of a commercial trout diet were determined. The ADF groups had reduced total mass gain and specific growth rates compared with DF fish, but photoperiod had no affect on growth for either of the feeding regime groups. In the ADF groups, the mean 24 h plasma thyroxine (T₄) and triiodothyronine (T₃) concentrations were significantly lower, both on days of feeding and days of fasting, than in DF fish held under all three photoperiod regimes, but for GH, only the 18L : 6D DF group was higher than the comparable ADF groups. There were no significant differences in mean 24 h plasma cortisol concentrations of DF and ADF groups. Diurnal patterns of plasma GH, cortisol, T₄ and T₃ were found in DF fish held under all three photoperiod regimes. Increases in plasma cortisol changes were associated with the onset of the light phase; elevations in plasma GH and T₄ concentrations were more closely associated with clock time, regardless of photoperiod; increases in plasma T₃ concentrations were strongly associated with time of feeding. In ADF groups, these diurnal changes in plasma GH, T₄ and T₃ concentrations were suppressed for both the fed and fast days, and plasma cortisol concentrations were suppressed on the fasting day. The observations are discussed in terms of the proposed anabolic, catabolic and growth regulating roles of these hormones in different growth and metabolic modifying situations in teleosts.     

IGF-I and branchial IGF receptor expression and localization during salinity acclimation in striped bass

The initial response of the IGF-I system and the expression and cellular localization of IGF type-I receptor (IGF-IR) were studied in the gill of a euryhaline teleost during salinity acclimation. Exposure of striped bass (Morone saxatilis) to hyperosmotic and hypoosmotic challenges induced small, transitory (<24 h) deflections in hydromineral balance. Transfer from freshwater (FW) to seawater (SW) induced an initial decrease in plasma IGF-I levels after 24 h in both fed and fasted fish. There was an overall decrease in liver IGF-I mRNA levels after SW transfer, suggesting that decreased plasma levels may be due to a decline in hepatic IGF-I synthesis. No changes were observed in gill IGF-I mRNA, but SW transfer induced an increase in gill IGF-IR mRNA after 24 h. Transfer from SW to FW induced an increase in plasma IGF-I levels in fasted fish. In fed fish, no significant changes were observed in either plasma IGF-I, liver, or gill IGF-I mRNA, or gill IGF-IR mRNA levels. In a separate experiment, FW-acclimated fish were injected with saline or IGF-I prior to a 24-h SW challenge. Rapid regain of osmotic balance following SW transfer was hindered by IGF-I. Immunohistochemistry revealed for the first time in teleosts that IGF-IR and Na(+)-K(+)-ATPase are localized in putative chloride cells at the base of the lamellae, identifying these cells in the gill as a target for IGF-I and IGF-II. Overall the data suggest a hyperosmoregulatory role of IGF-I in this species.     

Salinity tolerance of two tropical fishes, Oreochromis aureus and O. niloticus. I. Biochemical and morphological changes in the gill epithelium

Cichlids of the genus Oreochromis are fish of economic importance in African countries. They tolerate brackish water, however, with great variations between species. In this work, two species, both from the Ivory Coast but of different origins, O. niloticus (field and laboratory strains) and O. aureus (field strain) were compared during osmotic challenges (10, 20 and 30%o salinity) in order to provide physiological support for their specific behaviour when confronted with natural hypertonic environments. Tolerance to salinity was assessed by correlated observations on gill structure, plasma sodium levels and gill Na⁺/K⁺ ATPase activity. In fresh water (FW), all fish presented a gill epithelium structure characteristic of FW stenohaline fish: no chloride cells (CC) on the lamellae and few CC on the filaments. An increase in external salinity induced the proliferation of CC on filaments, a feature typical of seawater teleosts. This change in gill structure was accompanied by an increase of gill Na⁺/K⁺ ATPase activity. In the most tolerant strains, plasma Na⁺ did not change, indicating successful ion regulation in the hypertonic media. With regard to potential interest of field strains in fish culture, O. aureus acclimated more easily to brackish water than O. niloticus . Interestingly, O. niloticus , kept for several generations in the laboratory, performed best in our challenge studies. Plasma Na⁺ levels and gill CC proliferation upon transfer to an isotonic medium may be the parameters of choice when testing these fish for their response to a salinity change.     

Growth hormone (GH) treatment acts on the endocrine and autocrine/paracrine GH/IGF-axis and on TNF-α expression in bony fish pituitary and immune organs

There exist indications that the growth hormone (GH)/insulin-like growth factor (IGF) axis may play a role in fish immune regulation, and that interactions occur via tumour necrosis factor (TNF)-α at least in mammals, but no systematic data exist on potential changes in GH, IGF-I, IGF-II, GH receptor (GHR) and TNF-α expression after GH treatment. Thus, we investigated in the Nile tilapia the influence of GH injections by real-time qPCR at different levels of the GH/IGF-axis (brain, pituitary, peripheral organs) with special emphasis on the immune organs head kidney and spleen. Endocrine IGF-I served as positive control for GH treatment efficiency. Basal TNF-α gene expression was detected in all organs investigated with the expression being most pronounced in brain. Two consecutive intraperitoneal injections of bream GH elevated liver IGF-I mRNA and plasma IGF-I concentration. Also liver IGF-II mRNA and TNF-α were increased while the GHR was downregulated. In brain, no change occurred in the expression levels of all genes investigated. GH gene expression was exclusively detected in the pituitary where the GH injections elevated both GH and IGF-I gene expression. In the head kidney, GH upregulated IGF-I mRNA to an even higher extent than liver IGF-I while IGF-II and GHR gene expressions were not affected. Also in the spleen, no change occurred in GHR mRNA, however, IGF-I and IGF-II mRNAs were increased. In correlation, in situ hybridisation showed a markedly higher amount of IGF-I mRNA in head kidney and spleen after GH injection. In both immune tissues, TNF-α gene expression showed a trend to decrease after GH treatment. The stimulation of IGF-I and also partially of IGF-II expression in the fish immune organs by GH indicates a local role of the IGFs in immune organ regulation while the differential changes in TNF-α support the in mammals postulated interactions with the GH/IGF-axis which demand for further investigations.     

Extracellular ionic and acid-base adjustments of Atlantic salmon presmolts and smolts in fresh water and after transfer to sea water: the effects of ovine growth hormone on the acquisition of euryhalinity

In order to better understand the basis for the acquisition of euryhalinity by juvenile salmon and the role of endogeneous stimuli, experiments have been carried out to examine the dynamics of ionic and acid-base adjustments in fresh water (FW) and after direct transfer to full salinity (32 g l⁻¹) sea water (SW) (1) on Atlantic salmon smolt during the natural period of smoltification in spring, (2) on presmolt salmon in autumn, after intraperitoneal implantation of pellets containing ovine growth hormone (oGH). During parr-smolt transformation in FW, gill Na⁺/K⁺ ATPase activity gradually rises, the plasma osmolality (Posm) is unaffected and the total CO₂ of the plasma decreases significantly while whole blood pH fluctuates slightly. Direct transfer of smolt from FW to SW provokes only a slight increase in Posm and emphasizes the acid-base balance disruptions shown in FW. An oGHimplant in a presmolt stimulates gill Na⁺/K⁺ ATPase activity in FW, and affects the acid-base balance. After SW transfer (12 days after implantation), oGH treatment prevents the increase of osmotic pressure and the restoration of the acid-base, ionic equilibrium was faster for oGH-implanted fish than for sham-operated fish. These observations show that in FW smelting salmon develop most of the systems they need for migration and growth in SW and that oGH implants induce the development of physiological characteristics of smolts in a non-natural period of smolting.     

A one-year investigation of the relationship between serum GH levels and the growth of F4 transgenic and non-transgenic common carp Cyprinus carpio

It has been demonstrated that growth hormone (GH) transgenic fish often posses a trait for fast growth. Here, we investigated the growth of F₄'all-fish' GH transgenic carp Cyprinus carpio and their serum GH levels for a year. The results showed that F₄ all-fish GH transgenic carp were significantly larger in body mass ( c . two-fold, P < 0·001) and body length ( c . 1·3 fold, P < 0·001), compared with the non-transgenic group. The discrepancy of serum GH levels between the transgenic carp group and control group is 54 fold, when the water temperature was 12–34° C. When the water temperature decreased to 3·5° C in January, the discrepancy was 256 fold. The serum GH level of the transgenic group was relatively constant, while that of control varied greatly based on month and water temperature. The changes of growth rates between the transgenic group and the control group were similar for a year. Taken together, the results indicated that F₄ all-fish GH transgenic carp had not only higher and constant serum GH levels but also a significant fast-growing effect, compared with the control. To our knowledge, this is the first report on a one-year investigation of growth trait and serum growth hormone level in F₄ all-fish GH transgenic carp.