Somatotropin physiology — a review

Author: J.G. van der Walt
Year: 1994
Issue: 1
Volume: 24
Page: 1 - 9

The continuing search for improved efficiency has led to the introduction of exogenous growth and lactation promotants to enhance traditional animal production systems. Various species-limited somatotropins have been synthesized by means of recombinant gene technology, thereby allowing milk production in dairy cattle, and lean meat production in pigs, sheep and cattle to be manipulated. Growth hormone occurs in plasma in several forms, which overlap considerably with the structures of placental lactogen and prolactin. The peptide is stabilized by two disulphide bridges, and is folded into four α-helix regions. The somatogenic and lactogenic regions have been mapped, and two different binding sites found. Somatotropin is secreted episodically from the anterior pituitary with a striking ultradian rhythm in all mammals investigated thus far. The primary control over this release would appear to be neuroendocrinological, with somatostatin and releasing hormone (GHRH) playing the major roles, with considerable species differences. Starvation primes the system to optimally release somatotropin when feeding recommences. While sexual dimorphism in the release of somatotropin has been clearly demonstrated in the rat, most studies in other species have concentrated on male animals. Although somatotropin exhibits negative feedback on its release, it does not appear to have a direct effect on the somatotroph. In the ruminant at least, somatotropin may also be involved in satiety control. Other systems that have been implicated in the control of somatotropin release in ruminants include cholecystokinin, serotonin, dopamine and a-adrenergic receptors and plasma glucose concentrations, all via regulatory mechanisms in the hypothalamus, which change from pre- to postweaning (glycogenic to gluconeogenic). Recently, GHRH analogues, consisting of a series of short (5-6 amino acids) peptides similar to encephalin, as well as a nonpeptidyl secretagogue have been developed. Although GHRH normally contains 40-44 residues, it is only the 29 amino, acids% at the amino terminal end that are associated with the releasing activity. By replacing arginine residues with agmatine (decarboxylated arginine), it is possible to create analogues that have an increased potency of more than 50-fold. The short-term response to somatotropin in high-yielding Holstein cows varies between 2 and 5 kg/day. The dose response appears to be curvilinear and is not affected by the pattern of administration. There is no increase in feed intake during short-term administration of somatotropin, although in the long term increases of 10-25% have been found, when measured over the entire lactation. In such cases, feed intake increased gradually to match the increased milk production, owing to an improvement of feed conversion. The lactogenic effect does not appear to be mediated by any direct effect on the mammary gland. The most pronounced effect of somatotropin is the release of the insulin-like growth factors (IGF), chiefly from the liver, and to inhibit lipogenesis. Although somatotropin decreases body fat, non-esterified fatty acids only increase during a negative energy balance. Although studies in sheep generally support these contentions, the effect on growth is controversial. Average daily gain (ADG) and feed conversion efficiency (FCE) generally improve with treatment, accompanied by a fairly consistent 10 to 20% decrease in carcass fat. The major effect in pigs is anabolic, leading in general to a 10-20% increase in ADG, a 15-35% improvement in FCE, a 30-40% decrease in lipid deposition and a 20-30% increase in protein deposition. The optimum dose depends on whether optimal growth or maximal feed efficiency is required. Nile crocodiles (Crocodylus niloticus) also respond to treatment with human somatotropin, by increasing feed intake, gaining body weight and increasing body length. Somatotropin released into the blood stream is bound by one of the two specific proteins found in plasma, one with high affinity and one with low affinity. In man, about 50% of circulating somatotropin is complexed to binding proteins, which are low at birth, and increase to reach maximum values in young adults. By sequestering somato¬tropin, the high affinity binding protein substantially interferes with the interaction between somatotropin and its receptor. The clearance rate of the bound form is 10-fold lower than that of the free form. Although similar binding proteins are found in the rabbit, pig, mouse and rat, there is little in ovine and bovine species. The binding protein appears to be generated by one of two mechanisms: either a proteolytic cleavage of the receptor near the trans-membrane domain, or de novo synthesis from a truncated mRNA. The former mechanism has been demonstrated in man and rabbit, and the latter in pregnant mouse and rat. The receptor belongs to a superfamily which include those for, inter alia, prolactin, the interleukins, erythropoietin and the interferons. Somatotropin receptors have now been demonstrated in many tissues other than the liver, such as kidney and the cardiovascular and respiratory systems. The distribution of the receptor has also been described within the cell, even in the nucleus. It has been suggested that this receptor is synthesized locally to facilitate intracellular transport of somatotropin and/or to regulate transcription of IGF.

Keywords: growth hormone, mechanism, release, review, somatotropin, structure, synthesis
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