Molecular targets in acromegaly

Abstract

Molecular therapeutic targets in growth hormone (GH)-secreting adenomas range from well-characterized surface receptors that recognize approved drugs, to surface and intracellular markers that are potential candidates for new drug development. Currently available medical therapies for patients with acromegaly bind to somatostatin receptors, GH receptor, or dopamine receptors, and lead to attainment of disease control in most patients. The degree of control is variable: however, correlates with both disease aggressiveness and tumor factors that predict treatment response including somatostatin receptor subtype expression, granulation pattern, kinases and their receptors, and other markers of proliferation. A better understanding of the mechanisms underlying these molecular markers and their relationship to outcomes holds promise for expanding treatment options as well as a more personalized approach to treating patients with acromegaly.

Neuregulin 4 (Nrg4) cooperates with melatonin to regulate the PRL expression via ErbB4/Erk signaling pathway as a potential prolactin (PRL) regulator

“…12,13 Of note, the Nrg4 receptor ErbB4 is expressed in pituitary lacto-somatotroph cells. 14 We also found the high expression of adipokines Nrg4 in the human pituitary PRL cells in our study. Additionally, studies have revealed that in rat pituitary tumor cells, EGF exerts a promoting effect on the synthesis of PRL.…”

“…The N‐terminal EGF‐like polypeptide segment of Nrg4, with a molecular weight of 14 kDa, has been demonstrated to possess the ability to traverse the blood‐brain barrier 12,13 . Of note, the Nrg4 receptor ErbB4 is expressed in pituitary lacto‐somatotroph cells 14 . We also found the high expression of adipokines Nrg4 in the human pituitary PRL cells in our study.…”

Using a precision approach to optimize the drug therapy of patients with acromegaly syndrome

“…The Pituitary Gland -An Overview of Pathophysiology and Current Management Techniques humoral, imaging and pathomorphological predictors for preliminary stratification of clinically homogeneous patients with a clear clinical prognosis and response to treatment [16,17].…”

“…The changes in ion permeability resulting from the activation of the receptor lead to a critical decrease in the intracellular concentration of calcium ions and cAMP, which blocks the secretion of GH and the proliferation of somatotrophs. Activation of SSTRs and specific proteins involved in intracellular signal transmission (AIP, ZAC1, RKIP, E-cadherin, β-arrestin) promotes suppression of GH secretion, inhibition of proliferation, cell migration and angiogenesis [16,19,37].…”

“…In a prospective study evaluating the effectiveness of lanreotide (120 mg every 28 days) as a first-line therapy, it was shown that the normalization of GH levels and IGF-I after 24 and 48 weeks of treatment were observed in 23.4 and 30.6% of patients. Thus, a significant part of patients receiving fg-SRLs has partial or complete resistance, which is a consequence of the internal heterogeneity of somatotropin in relation to the receptor expression of SSTs and other target molecules affecting the therapeutic response [16][17][18].…”