Peptide Hormones

Abstract

Apart from hormones derived from single amino acids (e.g., amines such as norepinephrine) and those with a steroid structure, hormones can be broadly divided into peptides and glycoproteins. Peptide hormones may be small like oxytocin and vasopressin with only 9 amino acids, or somewhat larger, such as insulin and insulin-like growth factor (IGF-1) with 51 and 70 amino acids, respectively, and growth hormone with 191 amino acids. Clinically significant insulin-induced adverse events are hypoglycemia, hyperglycemia, diabetic coma, and hypersensitivity reactions (types I, III, and IV). Other peptide hormones approved for use as important therapies are glucagon, glucagon-like protein-1 (GLP-1), recombinant insulin-like growth factor-1, somatostatin, adrenocorticotropic hormone (ACTH), gonadotropin-releasing hormone (GnRH), and parathyroid hormone. In some cases, analogs, agonists, antagonists, and inhibitors have been developed to overcome the limited stability of the parent hormone. For example, GLP-1 peptide agonists exenatide, albiglutide, and dulaglutide are not degraded by the dipeptidase DPP-4 and synthesized non-peptide inhibitors (gliptins) of the enzyme, sitagliptin, and vildagliptin are useful orally active hypoglycemics for the treatment of diabetes 2. The GLP-1 receptor agonists carry an FDA black box warning of the finding of thyroid C-cell tumors in rats and, as a consequence, the agonists are contraindicated in patients with medullary thyroid carcinoma (MTC), or a family history of MTC. Pramlintide, a synthetic analog of amylin, slows gastric emptying and reduces postprandial rises in plasma glucagon. Children treated with the recombinant human growth hormone somatropin show a 30 % increased long-term cancer risk. Somatostatin peptide analogs, octreotide and pasireotide, given for acromegaly; vasopressin receptor antagonists (vaptans) for treatment of dilutional hyponatremia; the vasopressin analog desmopressin; terlipressin, a prodrug of lysine vasopressin; and the long-acting oxytocin agonist carbetocin and antagonist atosiban, both approved for obstetric use, are further examples of approved hormone derivatives. Risks associated with oxytocin include the possibility of fetal and maternal deaths due to rupture of the uterus, hypertensive episodes, subarachnoid hemorrhage, and water intoxication. ACTH is occasionally used in the form of cosyntropin for diagnosing adrenal insufficiency and GnRH agonists (e.g., leuprolide, goserelin) and antagonists (e.g., cetrorelix for prostate cancer) provide important therapies. Parathyroid hormone is a key regulator of calcium levels in the blood with an important role in mineral homeostasis and bone maintenance. An FDA black box warning for the possibility of the development of bone cancer is associated with its use.