SUN-087 Cell Type-specific Distribution And Signaling Function Of Somatostatin Receptors In The Anterior Pituitary

Abstract Disclosure: S. Sivcev: None. S. Constantin: None. K. Smiljanic: None. S. Sokanovic: None. P. Fletcher: None. A. Sherman: None. H. Zemkova: None. S.S. Stojilkovic: None. Somatostatin (SST) receptors (SSTRs) are Gi/o protein-coupled receptors containing five members, designated SSTR1-SSTR5. Their role in the control of somatotroph function has been extensively studied. It has also been suggested that these receptors are expressed in other pituitary cell types, but the specific distribution of SSTRs and their roles in electrical excitability and voltage-gated calcium signaling in these cells remain incompletely understood. Using qRT-PCR and single-cell RNA sequencing, we identified a cell type-specific distribution of SSTRs in rat pituitary cells: SSTR1 and SSTR2 were found in thyrotrophs, SSTR3 in gonadotrophs and lactotrophs, and SSTR2, SSTR3, and SSTR5 in somatotrophs, while SSTR mRNA was not detected in corticotrophs and melanotrophs. SST administration reduced hormone secretion across all SSTR-expressing cells, with the most pronounced effect in somatotrophs. Among endocrine cells, gonadotrophs and thyrotrophs spontaneously fire high-amplitude single action potentials, whereas lactotrophs and somatotrophs fire low-amplitude plateau-bursting action potentials in conjunction with calcium transients. Patch-clamp recordings revealed that the administration of SST blocked their electrical activity and, in some cells, hyperpolarized the membrane. Single-cell calcium imaging showed that SST reduced basal intracellular calcium levels in lactotrophs and somatotrophs, but only inhibited sustained, agonist-induced, extracellular calcium-dependent transients in gonadotrophs and thyrotrophs. The pattern of inhibition of electrical activity and calcium signaling was consistent with proposed inhibitory pathways: direct inhibition of voltage-gated calcium channels and indirect inhibition by cell type-specific hyperpolarization mediated by inwardly rectifying potassium channels. These results indicate that the action of SST in somatotrophs is enhanced by the expression of several SSTRs subtypes. The hypothalamic SST may also play a role in the electrical resynchronization of gonadotrophs, thyrotrophs, and lactotrophs during sustained somatotroph inhibition. The absence of SSTRs in corticotrophs and melanotrophs likely contributes to their increased excitability and readiness to respond to stress. Presentation: Sunday, July 13, 2025