Insulin and growth hormone stimulate somatostatin receptor (SSTR) expression by inducing transcription of SSTR mRNAs and by upregulating cell surface SSTRs

Abstract

This study examined the effects of insulin (INS) and growth hormone (GH) on mRNA and functional expression of somatostatin receptors (SSTRs). Rainbow trout liver was used as a model system to evaluate the direct effects of INS and GH on mRNA expression of three SSTR subtypes characterized previously from this species: SSTR1A, SSTR1B, and SSTR2. INS and GH directly stimulated steady-state levels of all SSTR mRNAs in a concentration- and time-dependent manner; however, the pattern of expression was hormone and SSTR subtype specific. INS stimulated SSTR2 expression to a greater extent than SSTR1A or SSTR1B expression, whereas GH stimulated SSTR2 and SSTR1B expression to a similar extent, with SSTR2 and SSTR1B expression being more responsive to GH than SSTR1A. Whether INS- or GH-stimulated SSTR expression resulted from altered rates of transcription and/or changes in mRNA stability also was investigated. Formation of nascent SSTR transcripts in nuclei isolated from rainbow trout hepatocytes was significantly stimulated by INS and GH. Neither INS nor GH, however, affected the stability of SSTR mRNAs. Functional expression of SSTRs was studied in Chinese hamster ovary (CHO-K1) cells stably transfected with SSTR1A or SSTR1B. Surface expression of functional SSTRs was stimulated by INS and GH. These findings indicate that INS and GH stimulate SSTR expression by regulating transcription of SSTR mRNAs and by increasing functional SSTRs on the cell surface, and they suggest that regulation of SSTRs may be important for the coordination of growth, development, and metabolism of vertebrates.

Immunohistochemical Detection of Somatostatin Receptor (SSTR) Subtypes 2A and 5 in Pituitary Adenoma from Acromegalic Patients: Good Correlation with Preoperative Response to Octreotide

“…Responsiveness to SSA therapy is directly related to the receptor status of the tumor. Previously, studies using in vivo techniques or by using cell cultures in vitro have been reported [33,34,43,44]. Detection of SSTR is achieved by mRNA analysis using RT-PCR or in situ hybridization and protein level analysis using radioligand binding studies [29,32,34,44].…”

“…Octreotide mainly binds to SSTR2 with high affinity and to SSTR5 and SSTR3 at about one-tenth of that affinity [28,30,43]. It is thought that the effects of octreotide depend on the SSTR subtypes expressed by that particular individual tumor.…”

“…Because SSTR reside in the cell membrane, it is suggested that cytoplasmic SSTR have low biological activity. Dimerization of SSTR is considered to be required for internalization and regulation of the receptor [28,43]. Here, we used a scoring system for immunopositivity of the cell membrane to classify and compare the level of SSTR expression.…”

Neuroendocrine regulation of somatic growth in fishes

“…Alternate forms of the SST-14 peptide containing a Pro2 residue (Pro2-SST-14) are derived from PPSST-2 [70]. Other forms of SST peptides are derived from PPSST-3 and PPSST-4 and have also been found in teleost fish [71,72]. All of these mature SST peptides are located at the C-terminal of SST precursors [72].…”

Somatostatin and the “Small-For-Size” Liver

“…Each SSTR associates with heterotrimeric guanine nucleotide-binding proteins (G-proteins) to mediate the inhibition of adenylyl cyclase activity, primarily, as well as mitogen-activated protein kinase and various phosphatases and ion channels [33,34]. Injury, cytokines, growth factors (including insulin and growth hormone, GH), and somatostatin itself regulate SSTR gene expression [35,36,37,38]. Initial responses of SSTR binding are diminished by continuous exposure via mechanisms of receptor desensitization, internalization, and degradation [35,39].…”