The Impact of Initial Energy Reserves on Growth Hormone Resistance and Plasma Growth Hormone-Binding Protein Levels in Rainbow Trout Under Feeding and Fasting Conditions

Abstract

The growth hormone (GH)-insulin-like growth factor I (IGF-I) system regulates important physiological functions in salmonid fish, including hydromineral balance, growth, and metabolism. While major research efforts have been directed toward this complex endocrine system, understanding of some key aspects is lacking. The aim was to provide new insights into GH resistance and growth hormone-binding proteins (GHBPs). Fish frequently respond to catabolic conditions with elevated GH and depressed IGF-I plasma levels, a condition of acquired GH resistance. The underlying mechanisms or the functional significance of GH resistance are, however, not well understood. Although data suggest that a significant proportion of plasma GH is bound to specific GHBPs, the regulation of plasma GHBP levels as well as their role in modulating the GH-IGF-I system in fish is virtually unknown. Two in vivo studies were conducted on rainbow trout. In experiment I, fish were fasted for 4 weeks and then refed and sampled over 72 h. In experiment II, two lines of fish with different muscle adiposity were sampled after 1, 2, and 4 weeks of fasting. In both studies, plasma GH, IGF-I, and GHBP levels were assessed as well as the hepatic gene expression of the growth hormone receptor 2a (ghr2a) isoform. While most rainbow trout acquired GH resistance within 4 weeks of fasting, fish selected for high muscle adiposity did not. This suggests that GH resistance does not set in while fat reserves as still available for energy metabolism, and that GH resistance is permissive for protein catabolism. Plasma GHBP levels varied between 5 and 25 ng ml^-1, with large fluctuations during both long-term (4 weeks) fasting and short-term (72 h) refeeding, indicating differentiated responses depending on prior energy status of the fish. The two opposing functions of GHBPs of prolonging the biological half-life of GH while decreasing GH availability to target tissues makes the data interpretation difficult, but nutritional regulatory mechanisms are suggested. The lack of correlation between hepatic ghr2a expression and plasma GHBP levels indicate that ghr2a assessment cannot be used as a proxy measure for GHBP levels, even if circulating GHBPs are derived from the GH receptor molecule.

Keywords: adiposity; fasting; growth hormone resistance; growth hormone-binding protein; salmonid.

Figure 1

(A) Plasma growth hormone (GH) levels, (B) plasma insulin-like growth factor I (IGF-I) levels, (C) plasma growth hormone-binding protein (GHBP) levels, and (D) hepatic expression of the growth hormone receptor gene 2a (ghr2a) in rainbow trout fed () or fasted () for 4 weeks (sampled at time 0 h) after which both groups were fed over a 72 h “refeeding” period. Data are presented as means ± SEM. Two-way ANOVA results on main effects (feeding regime and time) as well as the interaction between the main effects (F × T) are indicated in the panels as being non-significant (ns, p > 0.05) or significant at the levels of **p < 0.01 and ***p < 0.001. Post hoc analysis was carried out if main effects were significant. For “Feeding regime,” differences are indicated as *p < 0.05 or ***p < 0.001. For “time,” significant differences are indicated by different letters, lower case for fasted fish.

Figure 2

(A) Plasma growth hormone (GH) levels, (B) plasma insulin-like growth factor I (IGF-I) levels, (C) plasma growth hormone-binding protein (GHBP) levels, and (D) hepatic expression of the growth hormone receptor gene 2a (ghr2a) in fat line (FL, ) and lean line (LL, ) rainbow trout over a 4-week fasting period. Data are presented as means ± SEM. Two-way ANOVA results on main effects (strain and time) as well as the interaction between the main effects (S × T) are indicated in the panels as being non-significant (ns, p > 0.05) or significant at the levels of *p < 0.05, or ***p < 0.001. Post hoc analysis was carried out if main effects were significant. For “Strain,” differences are indicated as *p < 0.05. For “Time,” significant differences are indicated by different letters, lower case for LL fish and upper case for FL fish.