Endocrine Abstracts

Background: Besson A et al. described a patient with homozygous for C53S-hGH suffering from IGHD (JCEM2005 90:2493-9). They observed reduced ability of the mutant to bind and activate GHR in vitro. C53A-hGH lacks the disulfide bond between C53 and C165, which is conserved in GH/prolactin family.Methods: Mouse pituitary AtT-20 cells, HEK-293 and CHO-K1 cells were transfected with plasmids containing C53S, C53A or C53S/C165A cDNA. hGH from cell supernatant...

There is a high heterogeneity of human growth hormone (hGH), variation rising from the different genes in pituitary and placenta, alternative splicing, post-translational modifications, oligomerization and binding to the growth hormone binding protein (GHBP). Distinguishing between different variants remains problematic and there is still quite little information about the proportion of these variants in circulation of both healthy individuals and of patients with growth hormo...

Introduction: Two heterozygous missense mutations R77C and D112G have been identified in GH-1 gene of patients with short stature by Takahashi et al. These patients had high serum immunoreactive GH concentrations but low IGF-1 concentrations, indicating bioinactivity of their GH. Separation of GH in patients’ serum by isoelectric focusing revealed the coexistence of mutant and wild type (wt) GH. In order to understand the molecular mechanism of the isolated GH defi...

The physiological and pathophysiological significance of hGH isoforms remains to be fully elucidated. In order to study the two most abundant hGH isoforms 20 and 22 kDa hGH, we have generated monoclonal antibodies (mAbs) against 20 and 22 kDa hGH. The mAbs against 20 and 22 kDa were characterized for their specificity and epitopes with different binding assays as well as by Western blot. The mAb 1G12 against 20 kDa with lower than 0.05% cross reactivity to 22 kDa hGH combined ...

Background: Leptin has multiple functions including modulating energy homeostasis and the immune response. Leptin is an important target for therapy to modulate the immune response in several autoimmune diseases. Although the structure of leptin is known, that of its receptor remains unsolved. The aim of this project was to express and purify the extracellular domain the leptin receptor (ObR) in order to carry out functional and crystallisation studies to elucidate the mechani...

Background and aim: Aryl hydrocarbon receptor-interacting protein (AIP) is evolutionary conserved and widely distributed throughout organism. Broad interest for AIP comes from involvement of loss-of-function AIP mutations in pituitary adenoma pathogenesis. The role of AIP in normal pituitary function is largely unknown. AIP is co-localized with GH in somatotroph secretory vesicles. Serum AIP protein was proteomically identified. We aimed at investigating whether AIP and GH are...

GH consists of various molecular isoforms. Most abundant is 22 kDa-GH (80–90% of total GH), followed by 20 kDa-GH (5–15% of total GH). The biological significance of 20 kDa-GH remains unclear, but its effects appear comparable to those of 22 kDa-GH. Acromegaly is characterized by chronic GH excess. Data on GH isoforms in acromegaly are scarce, but an increased 20 kDa-/22 kDa-GH-ratio (20k-ratio) has been described. Our aims were to compare the 20k-ratio in a larger c...