Endocrine Abstracts (2012) 28 P238

Ultrastructural changes in somatotrophs and gonadotrophs in TPit null mice

Lok Yick1, Konstantin Khetchoumian2, Jacques Drouin2 & Helen Christian1

1Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom; 2Laboratory of Molecular Genetics, Institut de Recherches Cliniques de Montréal, Montréal, QC, Canada.

Tpit is a pituitary-specific transcription factor that is important for corticotroph terminal differentiation. In TPit null mice corticotroph cells do not differentiate and cells immunopositive for SF1, LH and FSH are observed in the intermediate lobe (Pulichino et al. 2003 Genes Dev). As the anterior lobe in TPit null mice showed a 50% decrease in cell number compared to wild-type (WT), and corticotrophs comprise only 5–7% of anterior lobe cells, we investigated changes in other pituitary cell types, specifically somatotrophs and gonadotrophs in TPit null mice. Anterior pituitary sections from female WT, heterozygous and TPit null four month old mice (n=4 of each) were immunogold-labelled for GH and examined by quantitative electron microscopy to determine somatotroph size, secretory granule characteristics and distribution. In addition, sections were immunogold-labelled for LH and FSH to compare gonadotroph ultrastructure in TPit null anterior and intermediate lobes. In TPit null mice there was a significant decrease in somatotroph number, cytoplasmic area and granule density (P<0.05 vs WT) suggesting decreased synthesis and storage of GH. Gonadotrophs in the TPit null intermediate lobe, however, appeared normal with no differences in secretory granule appearance or cell morphology compared to anterior lobe gonadotrophs. Secretory granules were immunopositive for LH and/or FSH as in WT and there was no significant difference in gonadotroph granule density between wild-type and TPit null mice. Although intermediate lobe gonadotrophs in TPit null mice were not different in size to TPit null anterior lobe gonadotrophs, these cells were significantly (P<0.05) reduced in area when compared to wild type gonadotrophs, in agreement with FACS analyses (Budry et al. 2011 PNAS). In conclusion, although corticotrophs comprise a relatively small proportion of the normal pituitary, these data suggest an important role in establishing other pituitary cell networks.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.

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