Endocrine Abstracts (2006) 11 P644

Effects of targeted ablation of GHRH neurons in mice on anterior pituitary somatotrophs and lactotrophs

A Miller1, P Le Tissier2, I Robinson2 & HC Christian1

1University of Oxford, Oxford, United Kingdom; 2National Institute of Medical Research, London, United Kingdom.

Animal and clinical models of GHRH excess suggest that GHRH provides an important trophic drive to pituitary somatotrophs. Mice in which GHRH neurons have been ablated using a novel viral ion channel transgene (GHRH-M2 mice) show marked anterior pituitary hypoplasia and GH deficiency although GH cells are present. GHRH-M2 mice are also deficient in prolactin which is surprising as GHRH has little or no direct effect on PRL synthesis or release (Le Tissier, Mol Endo 19). In mice two morphological subtypes of lactotroph have been described: Type 1 contain large irregular shaped granules whereas Type 2 contain smaller spherical granules. It is not known what signals influence the differentiation of Type 1 or Type 2 lactotrophs; however GHRH is one candidate. We have examined further the somatotroph and lactotroph populations in non-transgenic (NT) and GHRH-M2 mice. Anterior pituitary tissue from male and female NT and GHRH-M2 adult mice (n=6) was fixed, immunogold labelled for GH and PRL and examined by electron microscopy to determine the number, size, secretory granule population and secretory machinery of somatotrophs and lactotrophs. Somatotrophs, Type1 and Type 2 lactotrophs were identified in both genders irrespective of the absence of GHRH. Somatotroph numbers were significantly (P<0.01) reduced in male and female GHRH-M2 mice confirming the trophic drive of GHRH to somatotrophs. Female lactotroph and somatotroph morphology was unaltered compared to non-transgenic controls. However, male somatotrophs and Type 2 lactotrophs were smaller and contained significantly fewer (P<0.05) secretory vesicles. Type 1 lactotrophs in male GHRH-M2 mice were smaller, contained more dilated rough ER but no change in vesicle number. These data indicate (1) that male somatotrophs and Type 2 lactotrophs are less active in the absence of GHRH and (2) that GHRH influences lactotroph activity directly or indirectly. In conclusion, Type 1 and 2 lactotroph differentiation occurs independently of GHRH; however, alterations in male lactotroph morphology in GHRH-M2 mice suggests GHRH influences lactotroph function.

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