Endocrine Abstracts (2009) 20 P555

Characterisation of PARS, a novel putative pituitary regulator of hormone secretion

Marie Helene Reiter1, Greisa Vila1, Engelbert Knosp2, Ludwig Wagner1 & Anton Luger1

1Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria; 2Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.

We present data on open reading frame 62 encoded on human chromosome 6 (C6orf62), a gene whose protein expression and function has not been described to date. The gene product of C6orf62 was designated pituitary associated regulator of hormone secretion (PARS).

Initial gene expression screens showed that PARS transcription is differentially regulated in secreting and non-secreting pituitary adenomas, as well as in normal pituitary tissue. Inspired by these findings, C6orf62 was amplified by PCR from HEK293 cDNA using specific primers. To investigate the gene product of C6orf62, it was ligated into an expression vector with an N-terminal His-tag and expressed in E. coli. Western blotting using an anti-His antibody confirmed the expression of a 30 kDa recombinant His-tagged protein from C6orf62.

The open reading frame of PARS is comprised of five exons, which are encoded by 689 bp. The resulting protein consists of 229 amino acid residues. PARS is highly conserved throughout species, with 100% similarity to predicted mouse and rat homologues and consistently high conservation in zebrafish and chicken. However, no sequence similarity to proteins with known function was found. The PARS promoter contains numerous consensus binding sites for transcription factors, including CREB (cAMP response element binding), AP-1 (activator protein 1) and GR (glucocorticoid receptor).

Real-time PCR analysis revealed that PARS mRNA is highly expressed in pituitary tissue, and significantly down-regulated in pituitary adenomas, including somatotrophinomas, corticotrophinomas and prolactinomas, with particularly low expression in non-functioning pituitary macroadenomas. Its expression negatively correlates with tumour size. Ongoing experiments are investigating the role of PARS in pituitary hormone secretion and cell proliferation.

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