Hans Baumeister

Somatostatin receptor subtype 1 modulates basal inhibition of growth hormone release in somatotrophs

Somatostatin (SST) inhibits the secretion of many peptide hormones including growth hormone (GH). The various functions of SST are mediated through at least five different receptor subtypes (SSTR1–5), their precise physiological roles have not been solved yet. Here we report on studies concerning the functional role of SSTR1 in the modulation of GH release from somatotrophs. Primary cell cultures from pituitaries of wild‐type SSTR1 mice exposed to the SSTR1 selective somatostatin analog CH‐275 show reduction of basal levels of GH secretion whereas somatotrophs isolated from SSTR1 null mutant mice did not respond to the agonist‐mediated effect. This suggests that SSTR1 is involved in modulating basal GH levels in primary pituitary cell cultures and, together with SSTR2, may control the secretion of GH in the body.

The rat insulin-degrading enzyme: Molecular cloning and characterization of tissue-specific transcripts

The primary structure of the rat insulin‐degrading enzyme (IDE) was determined by cDNA analysis. Rat IDE, as well as the previously characterized homologs from human and Drosophila, contain the carboxyl‐terminal consensus sequence A/S‐K‐L for peroxisome targeting. A stretch of 43 bp surrounding an alternatively used polyadenylation site is highly conserved between rat and human, suggesting that it may contain important regulatory information. Northern blot analysis revealed two IDE transcripts of 3.7 and 5.5 kb in various tissues. Testis was found to be exceptional in having three different RNAs (3.7, 4.1 and 6.1 kb) at a relatively high abundance. The expression of the IDE gene in testis is correlated with sexual maturation.

A somatostatin receptor 1 selective ligand inhibits Ca2+ currents in rat insulinoma 1046-38 cells

Rat insulinoma 1046‐38 cells represent a model system to study β‐cell function. The mRNAs for sst1 and sst2, two of the five somatostatin receptors, were detected by reverse transcription polymerase chain reaction amplification in these cells. Displacement binding analysis suggested that sst1 represents the major somatostatin receptor subtype. The sst1 selective compound CH‐275 did not inhibit adenylyl cyclases while compounds that activated sst2 did. In contrast, CH‐275 caused a marked inhibition of voltage‐operated Ca2+ channels while the sst2 specific analog octreotide elicited a less pronounced effect suggesting that in rat insulinoma 1046‐38 cells sst1 preferably mediates the inhibition of Ca2+ channels.

Cloning, expression, pharmacology and tissue distribution of the mouse somatostatin receptor subtype 5.

The gene encoding the mouse somatostatin receptor subtype 5 has been isolated from a genomic library and the mRNA start point mapped to position −95 relative to the translational start codon. The promoter region is devoid of TATA and CAAT boxes but contains putative binding sites for AP‐1, AP‐2 and SP1 and response elements for glucocorticoids (GRE) and phorbol esters (TRE). The encoded receptor protein with a predicted molecular weight of 42.5 kDa is comprised of 385 amino acids and thus contains 22 and 21 amino acids more than rat and human counterparts. The extra amino acids are caused by another translational initiation codon located further upstream. In the region of overlap the mouse somatostatin receptor subtype 5 displays 96.7% sequence identity to the rat and 81.7% to the human homologue. Application of somatostatin‐14 and −28 to human embryonic kidney cells expressing the recombinant receptor resulted in the inhibition of forskolin‐stimulated adenylyl cyclase with comparable EC50 values. Consistent with the observed sequence relationship, the mouse somatostatin receptor subtype 5 displays a pharmacological profile that resembles the rat homologue more closely than the human counterpart. mRNA for the mouse somatostatin type 5 receptor has been detected in pituitary, kidney, spleen and ovary and, to a lesser extent, in brain, stomach, intestine and thymus but was not observed in heart, pancreas and liver.

Gene regulation of somatostatin receptors in rats

Using the rat as a model, the present article summarises the spatial, temporal and hormonal regulation of the somatostatin receptor subtypes and their mRNAs in brain and periphery and attempts to provide a molecular basis for somatostatin receptor gene regulation by the structural and functional analyses of their promoters.