What is it about?

Glycoprotein hormones are vital for normal physiological development, fertility, thyroid and placental function. Factors that disrupt normal secretion of these hormones produce dramatic disease effects. A very rare mutation in the gene coding for the luteinizing hormone beta subunit led us to a region common to all of the glycoprotein hormones. Specific disruptions of this region prevented normal secretion of all the glycoprotein hormones, indicating a vital area for regulation of these crucially-important hormones.

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Why is it important?

Glycoprotein hormones (TSH, LH, hCG and FSH) are essential for a series of physiological functions. Thus, mutations of these hormone peptides are extremely rare. Although some mutations e.g. in the signal peptide have obvious phenotypes, the one described here, in the LHb, affects its secretion despite being 20 amino acids away from the signal peptide. The missing amino acid is conserved in FSHb and hCGb and replaced for a similar amino acid (Arginine) in TSHb, deleting the amino acid either of these glycoproteins result in a retention phenotype as in LHb-K40del. Moreover, we have developed an assay to test this, and hitherto, glycoprotein mutations.

Perspectives

The mutation described in the article, deletion of 3 nucleotides corresponding to lysine (K) 40 in the protein, K20 in the mature peptide, stands against common knowledge where a secreted protein, once in the ER is either secreted or degraded. Here, our LHb mutant seems to stay on high concentrations intracellularly and does not get secreted. We will continue study this in more detail.

Professor Adolfo Rivero-Muller
Uniwersytet Medyczny w Lublinie

This study received the award for research publication of the year in the Journal of Endocrinology at the BES Harrowgate Meeting 2017

Adrian Daly
University of Liège

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This page is a summary of: A vital region for human glycoprotein hormone trafficking revealed by an LHB mutation, Journal of Endocrinology, September 2016, Bioscientifica, DOI: 10.1530/joe-16-0384.
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