Plasma somatomedin-C in fasted and refed rats: close relationship with changes in liver somatogenic but not lactogenic binding sites

Abstract

Circulating levels of somatomedins in man and rats are reduced by fasting and restored by refeeding. To determine the mechanisms for these alterations in somatomedin levels, the affinities and binding capacities of 125I-labelled bovine GH (somatogenic binding sites) and of 125I-labelled ovine prolactin (lactogenic binding sites) were assessed in liver homogenates from fasted and refed rats. Correlations were made with plasma immunoreactive somatomedin-C (Sm-C) and plasma insulin.During fasting and refeeding there was a close temporal relationship between the fall and the rise of plasma levels of Sm-C and insulin, and the number of hepatic GH binding sites. After fasting for 1 day, plasma Sm-C dropped by 68% and plasma insulin by 76% when compared with values before fasting. At the same time, GH binding capacity was significantly reduced (7\m=.\3\ m=+-\ 2\ m=. \ 8(s.e.m.) pmol/liver v. controls, 20\m=.\3 \ m=+-\ 2\ m=. \ 1 pmol/liver; P < 0\ m=. \ 01) . Refeeding for 24h normalized plasma insulin levels and restored GH binding capacity to values before fasting (13\m=.\2 \ m=+-\2\m=.\4v. 20\m=.\3\ m=+-\ 2\m=.\1 pmol/liver; P > 0\ m=. \ 05) . Plasma Sm-C rose significantly with refeeding and returned to initial values at day 4 of refeeding (0\m=.\82 \ m=+-\ 0\m=.\10v. 0\m=.\77\ m=+-\ 0\m=.\07 units/ml; P > 0\ m=. \ 05) .In contrast, changes in prolactin binding sites correlated poorly with changes in plasma Sm-C. There was a modest decline with fasting significant only after 72 h (6\m=.\8 \ m=+-\ 0\ m=. \ 6v.13\m=.\9 \ m=+-\ 3\m=.\2 pmol/liver; P < 0\ m=. \ 05), and refeeding for 24 h did not restore prolactin binding (5\m=.\7 \ m = + -\1\m=.\2 pmol/liver).Since a number of reports suggest that fasting induces a state of tissue insensitivity to GH, our findings suggest that the reduction in hepatic GH binding capacity might be a mechanism for the fasting-induced reduction in Sm-C. The reduction in plasma insulin, which accompanies fasting, might play a permissive role in the intracellular metabolic events involved in Sm-C and GH receptor regulation.

Increased Expression of Fibroblast Growth Factor 21 (FGF21) during Chronic Undernutrition Causes Growth Hormone Insensitivity in Chondrocytes by Inducing Leptin Receptor Overlapping Transcript (LEPROT) and Leptin Receptor Overlapping Transcript-like 1 (LEPROTL1) Expression

“…In many experimental models food restriction is associated with reduced skeletal growth, with such association primarily resulting from impaired growth hormone action (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). In a previous study we demonstrated that mice undergoing 4 weeks of food restriction exhibited increased expression of Fgf21 (both in the liver and in the growth plate), growth hormone (GH) 3 insensitivity, and a concomitant reduction of their body linear growth and growth plate chondrogenesis (17).…”

The effect of growth hormone treatment on growth in zinc deficient rats

“…Fasting appears to decrease GU binding in the liver because of redueed numbers of GH receptors (Maes ~ al., 1983;1984a;1984b to promote growth (Thissen ~~, 1990). A zinc deficient rat is not in a state of nutritional sufficiency.…”

GH and IGF-I binding sites in adipose tissue, liver, skeletal muscle and ovaries of feed-restricted gilts

“…A reduction of GH binding in liver has been observed in rats [17,37], cattle [4] and sheep [2]. It has also been reported that feed restriction decreases GHR mRNA levels in the liver of young pigs [9], whereas it increases these levels in peripubertal gilts [7].…”