Endocrine Abstracts

CD38 is an enzyme which catalyses the production of the second messengers cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate which mobilize calcium from ryanodine-sensitive intracellular calcium stores. Intracellular calcium is well known to be important for mobilisation of secretory granules to the plasma membrane in preparation for exocytosis and CD38 signalling has recently been demonstrated to increase posterior pituitary oxytocin release (Jin et al. Nature 2007 446 41). However, little is known regards CD38 signalling in the anterior pituitary. Here, we test the hypothesis that somatotroph GH secretion would be impaired and excess storage of secretory granules would result in CD38 null mice. Anterior pituitary tissue from male and female wild-type (WT) and CD38 null mice (n=4 of each) was immunogold labelled for GH and examined by quantitative electron microscopy to determine somatotroph size, secretory granule characteristics and distribution. Initial Western blot analysis revealed CD38 immunoreactivity in anterior pituitary and double-labelling immunofluorescence labelling for GH and CD38 demonstrated CD38 colocalisation in somatotrophs. In male mice no significant difference in somatotroph size, secretory granule size or number were measured in CD38 null mice versus WT. However, in female CD38 null mice there was a significant (P<0.05 versus WT) increase in cell size, secretory granule diameter and number suggesting increased storage of GH. Furthermore, there was a decrease in the percentage of secretory granules within a 400 nm margin of the plasma membrane indicating that fewer granules were distributed adjacent to sites of secretion. Radioimmunassay demonstrated that GH content was significantly (P<0.05) increased in CD38 null female mice versus WT but not significantly different in WT and CD38 null male mice In conclusion, the data are consistent with the hypothesis that the absence of CD38 leads to increased storage in somatotrophs and suggests a role in the exocytosis of GH in females.