Endocrine Abstracts (2010) 22 OC5.4

One hormone, two functions: the chorionic gonadotropin in New World Monkeys

Christian Adams1, Alexander Henke2 & Jörg Gromoll1

1Centre of Reproductive Medicine and Andrology, Münster, Germany; 2Medical Research Council, Human Reproductive Science Unit, Edinburgh, UK.

Objective: The LH and chorionic gonadotropin (CG) are essential for reproduction and male sexual development. While LH induces tesosterone production, CG is essential for the establishment of pregnancy. In the New World Monkeys (NWM) the initial duplication of the ancestral LH-beta subunit (LHB) gene, which gave rise to the novel CG-beta subunit (CGB) gene, was followed by a genomic rearrangement event, leading to CGB expression in pituitary and placenta, whereas LHB became a pseudogene.

The aim of this study was to analyse the regulatory mechanisms triggering pituitary and placenta specific CGB expression in the marmoset (Callithrix jacchus).

Methods: DNA-isolation, RT-PCR, DNA sequencing of the CGB gene, bisulfite analyses, Dual-Luciferase-Assays and transfection of BeWo cells.

Results: The marmoset employs a system in which two different promoters, joined to two different exon 1, regulate the expression of the CGB gene. In the pituitary conventional exon 1 (including the exons of CGB 2 and 3) is driven by a pituitary-specific promoter, while novel exon 1 (plus the other two exons) is the pre-dominant form in the placenta. The placental full length core promoter (600 bp) displays a very high luciferase activity when transfected into the trophoblastic BeWo cell line. No change can be observed in promoter activity in when the promoter was truncated up to 360 bp. Additional trucation, when several transcription binding sites were removed decreases activity by 50%. Furthermore the placental promoter contains a distinct CpG island, which is absent in the pituitary promoter. This might indicate that CpG methylation plays a role in the tissue-specific expression of CGB.

Conclusion: Our findings in the marmoset give an insight into the tissue-specific regulation of of CGB by different promoter and start exons. This underlines the plasticity of the primate LH/CG hormonal system and represents an interesting trait in the evolution of hormones.

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