Identification and Modulation of a Growth Hormone-Binding Protein in Rainbow Trout (Oncorhynchus mykiss) Plasma during Seawater Adaptation

To gain a better understanding of the mechanisms by which cortisol suppresses growth during chronic stress in fish, we characterized the effects of chronic cortisol on food intake, mass gain, the expression of appetite-regulating factors, and the activity of the GH/IGF axis. Fish given osmotic pumps that maintained plasma cortisol levels at w70 or 116 ng/ml for 34 days were sampled 14, 28 and 42 days post-implantation. Relative to shams, the cortisol treatments reduced food intake by 40-60% and elicited marked increases in liver leptin (lep-a1) and brain preoptic area (POA) corticotropin-releasing factor (crf) mRNA levels. The cortisol treatments also elicited 40-80% reductions in mass gain associated with increases in pituitary gh, liver gh receptor (ghr), liver igfI and igf binding protein (igfbp)-1 and -2 mRNA levels, reduced plasma GH and no change in plasma IGF1. During recovery, while plasma GH and pituitary gh, liver ghr and igfI gene expression did not differ between treatments, the high cortisol-treated fish had lower plasma IGF1 and elevated liver igfbp1 mRNA levels. Finally, the cortisol-treated fish had higher plasma glucose levels, reduced liver glycogen and lipid reserves, and muscle lipid content. Thus, our findings suggest that the growth-suppressing effects of chronic cortisol in rainbow trout result from reduced food intake mediated at least in part by increases in liver lep-a1 and POA crf mRNA, from sustained increases in hepatic igfbp1 expression that reduce the growth-promoting actions of the GH/IGF axis, and from a mobilization of energy reserves.

Section: Discussionmentioning

confidence: 99%

Chronic cortisol and the regulation of food intake and the endocrine growth axis in rainbow trout

Madison

Tavakoli

Krämer

et al. 2015

“…Those species include cow, horse, pig, sheep, goat, chicken (Davis et al 1992, Bingham et al 1994, Jammes et al 1996, Amit et al 1997, turtle (Sotelo et al 1997) and trout (Sohm et al 1998). With the exception of trout, most of these vertebrates possess a high-affinity moiety in the range of 50-70 kDa.…”

Section: Journal Of Endocrinology (2002) 175 55-59mentioning

confidence: 99%

Structure and regulation of expression of the mouse GH receptor

Talamantes¹,

Ortiz²

2002

GH-binding protein (GHBP) in the mouse consists of a ligand-binding domain, which is identical to the extracellular portion of the GH receptor (GHR), and a hydrophilic C-terminal domain, in place of the transmembrane and intracellular domains of the GHR. The two proteins are encoded by separate mRNAs which are derived from a single gene by alternative splicing. Determination of the gestational profiles of GHR and GHBP mRNA expression in mouse liver and placenta shows that in the liver, the 1·4 kb mRNA corresponding to the mouse GHBP increases approximately 20-fold between non-pregnant and late pregnant mice, whereas the relative increase in the expression of the 4·2 kb mouse GHR was 8-fold. The rise in the steady-state levels of both mRNAs began on day 9 of gestation. Mouse GHBP mRNA levels continue to rise until day 15 of pregnancy, while GHR mRNA abundance reaches a plateau by day 13. By elucidating the temporal changes in GHR and GHBP mRNA abundance during pregnancy and lactation in multiple maternal tissues and by assessing the ontogeny of these mRNAs in fetal and early postnatal mouse liver, our studies have demonstrated that the alternative splicing of mouse GHR/GHBP mRNA precursor is regulated in a tissue-, developmental stage-and physiological state-specific manner. In vitro studies using hepatocytes in culture have begun to elucidate the hormonal factor(s) involved in the gestation control of the expression of GHR and GHBP. Treatment of hepatocytes with GH or estradiol (E2) alone did not have any effect on the cellular concentrations of GHBP and GHR. However, the combination of E2 and GH up-regulated the cellular concentrations of GHBP and GHR 2-to 3-fold. GHBP and GHR mRNA concentrations were also up-regulated 2-to 3-fold. ICI 182-780, a competitive inhibitor of E2 for the estrogen receptor (ER), at different concentrations inhibited the E2-and GH-induced stimulation of GHBP and GHR. Furthermore, ER concentrations increased 5-to 7-fold in hepatocytes treated with E2 and GH compared with those in untreated cells or cells treated with either E2 or GH alone. Our studies in the mouse suggest that GHBP is an important cell-surface receptor for GH in the liver. These studies postulate that an arginine-glycine-aspartic acid sequence found on mouse GHBP but absent in other species is responsible for the association of GHBP with the plasma membrane by binding to one or more integrins on the surface of liver cells.

“…Amit et al (1992) measured the affinity constants for serum GHBPs in a number of mammalian species, including rabbit, rat, mouse, sheep, cow, horse, cat, monkey, and human, and reported that the B max varied between 140 fmol/ml serum and 19 200 fmol/ml serum (Amit et al 1992). Among other species studied to date, turtle GHBP was found to have a B max of 1080 fmol/ml serum (Sotelo et al 1997), whereas the B max values for serum GHBPs from rainbow trout (Sohm et al 1998) and chicken (Davis et al 1992) were reported to be remarkably higher, raging from 1·3 10 5 to 1·5 10 6 fmol/ml serum or greater. The physiological significance for such large variations in B max value between different species remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study (Sohm et al 1998) indicated that binding of rainbow trout GH to homologous serum was of low affinity (3·8 10 8 M -1 ), although binding of human GH to rainbow trout serum was of higher affinity (1·2 10 9 M -1 ). It is not clear why there are such large variations in the binding affinity of teleost GHBPs.…”

Section: Discussionmentioning

confidence: 99%

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Identification of serum GH-binding proteins in the goldfish (Carassius auratus) and comparison with mammalian GH-binding proteins

Zhang

Marchant²

1999

The present study constitutes the characterization of a specific, high-affinity GH-binding protein (GHBP) in the serum of a teleost, the goldfish (Carassius auratus). GH-binding assay and ligand blotting techniques were employed to identify GHBPs in goldfish serum and hepatocyte culture medium. The binding characteristics and apparent molecular weights (M r ) of goldfish GHBPs were also compared with those of rabbit and rat. LIGAND analysis identified a single class of high-affinity and lowcapacity binding sites for iodinated recombinant carp GH (rcGH) in the goldfish serum, with an association constant (K a ) of 20·1 10 9 M 1 and a maximum binding capacity (B max ) of 161 fmol ml 1 serum. A single class of binding sites for iodinated recombinant sea bream GH and bovine GH (bGH) was also found in goldfish serum, but with a much lower affinity than that of rcGH. The binding affinity for iodinated bGH in rabbit and rat sera was found to be similar to that reported previously. Ligand blotting revealed multiple forms of GHBPs in sera of goldfish, rabbit and rat with M r ranging from 70 kDa to 400 kDa and 27 kDa to 240 kDa under non-reducing and reducing conditions respectively. A prominent band with M r of 66 kDa and a minor band with M r of 27 kDa were observed to occur in sera from all three species under reducing conditions. Iodoacetamide promoted the shedding of three GHBPs with M r of 25, 40 and 45 kDa from the cultured goldfish hepatocytes. The appearance of all bands was completely inhibited by the presence of excess unlabeled rcGH. Our results provide clear evidence that a GHBP exists in the goldfish and indicate that more information on teleost GHBPs is needed if the physiology of growth in teleosts is to be fully understood.