Endocrine Abstracts

Pituitary growth hormone (GH) is released in a highly pulsatile fashion in response to stimuli from its hypothalamic regulators, GH releasing hormone (GHRH) and somatostatin (SRIF), as well as feedback from peripheral signals. This interplay is complex, and still poorly understood. GHRH is a major factor in controlling pituitary GH synthesis and somatotroph cell number as well as GH secretion, and lack of GHRH or its receptor cause profound somatotroph hypoplasia and dwarfism....

The hGH gene is expressed in epithelial cells of the normal human mammary gland. Increased epithelial expression of the hGH gene is associated with the acquisition of pathological proliferation, and the highest level of hGH gene expression is observed in metastatic mammary carcinoma cells. Autocrine hGH production in human mammary carcinoma cells results in increased cell proliferation and survival associated with alterations in morphology. We have further demonstrated that au...

Using the currently available somatostatin receptor (sst) ligands octreotide and lanreotide, that are mainly sst2 agonists, about 60% of patients with acromegaly are adequately controlled. This prompted the development of new drugs targeting other sst subtypes or other receptors that are also expressed on adenomatous cells. BIM 23244 characterized by a high affinity for sst2 and sst5 had been found in vitro to allow a stronger inhibition of GH secretion than octreotide ...

GH acts through a cell surface receptor, GHR, which is a member of the type 1 cytokine receptor family. Cytokine receptors have a single trans-membrane domain and dimerisation is required to activate intra-cellular signalling pathways. In common with other cytokine receptors the extra-cellular domain of the GHR is proteolitically cleaved and circulates as a binding protein. Under physiological conditions GH is in part bound in the circulation and the complex with the binding p...