Acromegaly is a rare life-shortening disease caused by elevated levels of growth hormone (GH) secreted by a tumor on the pituitary gland. Treatments include somatostatin analogs, which activate somatostatin receptor 2 (SSTR2), reducing GH secretion and tumor size.
Acromegaly progresses slowly, commonly going years before diagnosis. The first signs of acromegaly are often the changes to the sufferer’s physical appearance. The hands and feet enlarge, leading to increased ring and shoe sizes. The face gradually becomes disfigured – characteristic features of acromegaly patients are a protruding jaw and brow, enlarged tongue and nose, thickened lips, and spacing between teeth. Other possible symptoms include a deepening of the voice, increased perspiration, carpal tunnel syndrome, and sleep apnea. Acromegaly can lead to arthritis, diabetes, cardiovascular problems, respiratory disease, and other serious conditions, and hence a shortened lifespan. If acromegaly occurs prior to puberty, it results in gigantism (exceptional height).
Acromegaly is caused by persistent elevated levels of growth hormone, secreted by a pituitary adenoma, a noncancerous tumor formed from the cells of the pituitary gland that secrete the hormone in a regulated manner in healthy individuals. Somatostatin (SST) is produced by the hypothalamus, and binds to somatostatin receptors (G-protein coupled receptors) in the pituitary gland, activating second-messenger signaling, and ultimately resulting in attenuation of the frequency and magnitude of GH secretion. Therefore, the use of agonists of somatostatin receptors is a treatment strategy for acromegaly, alongside surgery and radiotherapy.
There are five subtypes of somatostatin receptors. Somatostatin receptor 2 is very highly expressed in GH-secreting adenomas, as is somatostatin receptor 5 (SSTR5), with the other subtypes expressed less frequently. These are targeted by the somatostatin analogs octreotide and lanreotide, which bind with high affinity to SSTR2, moderate affinity to SSTR5, and low or no affinity to the other subtypes. These long-acting drugs thus suppress the tumor’s GH secretion; they also inhibit tumor growth and can reduce tumor volume. However, the degree of success of treatment with the somatostatin analogs varies between patient, thought to be due to the particular density of SSTR2 and SSTR5 in their adenoma. A study by Plöckinger et al. used antibodies to analyze somatostatin receptor expression in tumors removed from acromegaly patients, some of whom had undergone preoperative octreotide treatment. Somatostatin receptor 2 was found in all adenomas from patients who had not received octreotide. In the pretreated tumors, expression of SSTR2 correlated with the decrease in GH levels measured in those patients; in the tumors of patients classified as non-responders, the SSTR2 was absent, suggesting that it had been down-regulated in response to the octreotide.
Resistance/response of adenomas to somatostatin analogs is not yet fully understood, so is a current research topic. Furthermore, as no existing treatment for acromegaly is completely effective for all patients, new drugs and treatment plans are being investigated.
Novus Biologicals offers somatostatin receptor 2 reagents in the form of antibodies, lysates, peptides and proteins, and RNAi for your research needs.
Novus Biologicals offers somatostatin receptor 2 reagents for your research needs including:
Written by Carly Hammond
