Growth Hormone Related Peptides

Growth Hormone Related Peptides

Definition
Growth hormone (GH), or somatotropin, is produced in the anterior portion of the pituitary gland. A number of effects of GH is mediated by a insulin-like growth factor-1 (IGF-1) secreted from the liver and other tissues.

Discovery
The growth hormone-releasing hormone (GHRH) gene produces a precursor molecule that contains GHRH and a carboxyl-terminal peptide that have named GHRH-related peptide (GHRH-RP). This peptide, like GHRH, stimulates the expression of stem cell factor (SCF), an important reproductive and hematopoietic cytokine, in vitro and in vivo. Using primary cultures of rat Sertoli cells, Steinmetz et al., in 2000 compared the time course of action and the level of SCF stimulation seen following treatment with GHRH-RP and GHRH 1. Growth hormone-releasing hormone is released from neurosecretory nerve terminals, and is carried by the hypothalamo-hypophyseal portal system to anterior pituitary gland. It stimulates GH secretion by stimulating the growth hormone releasing hormone receptor 2. A new Arg-Phe-NH2 (RFamide) peptide has been discovered in the amphibian hypothalamus. The cell bodies and terminals containing this peptide were localized in the suprachiasmatic nucleus and median eminence, respectively. This peptide was further revealed to have a considerable growth hormone (GH)-releasing activity in vitro and in vivo and hence designated as frog GH-releasing peptide (fGRP) 3.

Structural Characteristics
GH, or somatotropin, is a protein hormone of 191 amino acids that is produced in the anterior portion of the pituitary gland 1. Human placental lactogen (hPL), GH, and prolactin (PRL) comprise the growth hormone family. All have about 200 amino acids, 2 disulfide bonds, and no glycosylation. Although each has special receptors and unique characteristics to their activity, they all possess growth-promoting and lactogenic activity. Mature GH (22,000 daltons) is synthesized in acidophilic pituitary somatotropes as a single polypeptide chain 4, 5. Molecular cloning of cDNA encoding the fGRP precursor polypeptide revealed that it encodes fGRP and its putative gene-related peptides (fGRP-RP-1, -RP-2, and -RP-3). Subsequently, authors have identified these putative fGRP-RPs as mature peptides and analyzed their hypophysiotropic activities. Only fGRP-RP-2 stimulated the release of GH and prolactin (PRL) in vitro and in vivo. Thus, in addition to fGRP, fGRP-RP-2 acts as a hypothalamic factor on the frog pituitary to stimulate the release of GH and PRL 3.

Mode of Action
GH or somatotropin’s release is controlled by the opposing actions of two hormones: growth hormone-releasing hormone, which stimulates both the synthesis and secretion of growth hormone; and somatostatin, which inhibits its release. GH plays a major role in the regulation of several complex physiologic processes in almost every organ and system in the body. It promotes growth in soft tissues, cartilage and bones; increases the synthesis of protein, RNA and DNA; decreases carbohydrate utilization and increases fat utilization. GH promotes bone growth by exerting a stimulating effect on the differentiation of proliferative chondrocytes or stem cell chondrocytes. A number of effects of GH are mediated by insulin-like growth factor-1 (IGF-1) secreted from the liver and other tissues. Excessive production of growth hormone causes gigantism in youth and acromegaly in adults. Lack of the hormone in children results in dwarfism 4, 5. In humans, growth hormone promotes gluconeogenesis and is consequently hyperglycemic. It promotes amino acid uptake by cells, with the result that GH therapy puts an organism into positive nitrogen balance, similar to that seen in growing children.

Functions
Growth hormone-releasing hormone also promotes slow-wave sleep directly. Growth hormone is required for normal postnatal growth, bone growth, regulatory effects on protein, carbohydrate, and lipid metabolism 1.

Genetic deficiencies, there are a number of genetic deficiencies associated with GH. GH-deficient dwarfs lack the ability to synthesize or secrete GH, and these short-statured individuals respond well to GH therapy. Pygmies lack the IGF-1 response to GH but not its metabolic effects; thus in pygmies the deficiency is post-receptor in nature.

Acromegaly, the defect in these individuals is clearly related to an inability to respond to GH by the production of IGF-1. The production of excessive amounts of GH before epiphyseal closure of the long bones leads to gigantism, and when GH becomes excessive after epiphyseal closure, acral bone growth leads to the characteristic features of acromegaly 5.

Lipolytic, growth hormone is lipolytic, inducing the breakdown of tissue lipids and thus providing energy supplies that are used to support the stimulated protein synthesis induced by increased amino acid uptake.

References
1. Steinmetz R, Lazzaro N, Rothrock JK, Pescovitz OH (2000). Effects of growth hormone-releasing hormone-related peptide on stem cell factor expression in cultured rat sertoli cells. Journal Endocrine, 12(3):323-327.
2. Obál F, Krueger J (2001). The somatotropic axis and sleep. Rev Neurol., 157(11):12-15.
3. Ukena K, Koda A, Yamamoto K, Iwakoshi-Ukena E, Minakata H, Kikuyama S, Tsutsui K (2006). Structures and diverse functions of frog growth hormone-releasing peptide (fGRP) and its related peptides (fGRP-RPs): a review. Journal of Experimental Zoology Part A: Comparative Experimental Biology, 305(9):815-821.
4. Englander EW, Gomez GA, Greeley GH Jr (2004). Alterations in stomach ghrelin production and in ghrelin-induced growth hormone secretion in the aged rat. Mech. Ageing Dev., 125(12):871-875.
5. Sonntag WE, Lynch C, Thornton P, Khan A, Bennett S, Ingram R (2000). The effects of growth hormone and IGF-1 deficiency on cerebrovascular and brain ageing. J. Anat., 197(4):575-585.

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