Signal Transduction in Pituitary Functions

Abstract

Signal transduction plays a crucial role in the intricate functioning of the pituitary gland. Dopamine receptor type 2 (DRD2) signaling is representative. The actin-binding protein filamin A (FLNA) is essential for the expression and signaling of dopamine receptor type 2 (DRD2) in GH- and PRL-secreting pituitary tumors (PitNETs). FLNA acts, facilitating DRD2 signal transduction and influencing tumor responsiveness to dopaminergic drugs and somatostatin receptor ligands. Remarkably, when FLNA is phosphorylated at Ser2152 (P-FLNA), its role transitions from being a scaffold that facilitates SSTR2 signal transduction to becoming a signal termination protein that impairs SSTR2’s antitumoral effects in GH-secreting PitNETs. Activation of the cAMP pathway and stimulation of DRD2 agonists impact P-FLNA levels. Overexpression of a phosphomimetic (S2152D) FLNA mutant prevents DRD2’s antiproliferative effects, emphasizing the role of P-FLNA in DRD2 signaling. These include the phosphorylation of Janus Kinase (Jak) 2 and Signal Transduction and Activator of Transcription (STAT) 5. Once phosphorylated, these proteins modulate the activity of specific genes. For instance, they enhance the expression of tyrosine hydroxylase, which stimulates dopamine production, and activate the beta-casein gene, promoting milk protein synthesis. In lower vertebrates, the pituitary gland exhibits signal transduction mechanisms related to the glucagon-like peptide-1 (GLP-1) system.