Chorionic gonadotrophin β subunit mRNA but not luteinising hormone β subunit mRNA is expressed in the pituitary of the common marmoset (Callithrix jacchus)

Abstract

The pituitary gonadotrophins LH and FSH are responsible for regulation of gametogenesis in the testis and ovary. Chorionic gonadotrophin (CG), a third closely related glycoprotein hormone derived by gene duplication of the LHβ gene and secreted by the placenta in primates, is essential for the rescue of the corpus luteum and maintenance of pregnancy. We have recently shown that marmoset (m) CGβ mRNA is highly expressed in the pituitary of the common marmoset (Callithrix jacchus) and that LH is less active than human CG in activating the human LH receptor lacking exon 10. To investigate further which gonadotrophin is the actual ligand of the LH receptor (LHR) of the marmoset monkey that naturally lacks exon 10, we identified and characterised the genomic organisation of the mLHβ gene and its expression. Intergenic PCR amplification of the region encompassing the mLHβ and the mCGβ genes revealed that, surprisingly, mCGβ is located 20 kbp upstream of the LHβ gene, whereas in other species the intergenic distance is approximately 2-3 kbp. Sequence analysis of the mLHβ coding region showed 70% identity to mCGβ and 90% identity to human LHβ at the amino acid level. Both gonadotrophin β subunits are present at the genomic level, but RT-PCR of pituitary and placental total RNA using specific oligonucleotides for mCGβ and mLHβ showed high expression of mCGβ mRNA in both tissues, whereas LHβ was expressed neither in the pituitary nor in the placenta. Thus mLHβ mRNA is lacking in the marmoset pituitary. Immunohistochemistry of marmoset pituitaries showed that mCG was confined to the gonadotrophes, and partly co-localised in cells stained positively for FSH. Western blot analysis confirmed the presence of mCG in the pituitary. Northern blot analysis using mCGβ as a probe displayed one transcript of 0.7 kb in the pituitary and detected two transcripts of 1.1 kb and 2 kb in the marmoset placenta. Our results suggest that, in the common marmoset, CG is the only gonadotrophin with luteinising function that is present in the pituitary. We postulate that, owing to an unknown mutational event in evolution, expression of mLH was completely abolished, and CG - which, unlike LH, acts normally even when exon 10 is missing from the LHR - took over its function. © 2004 Society for Endocrinology.