Tag Archives: hypogonadotrophic hypogonadism

Sirtuin protein at the start of GnRH neuron migration

The GnRH neurons are unique among the hypothalamic neurons that they originate not in hypothalamus itself, but in the vomeronasal organ of the olfactory bulb and move (in the mouse) between day 10 and 17 of embryonic development into the hypothalamus via the forebrain. When this wandering is impaired, there is not any GnRH synthesis in the hypothalamus due to missing GnRH neurons, a phenomen called Kallmann syndrome, and subsequently the patient undergo hypogonadotrophic hypogonadism.

In a report in Molecular Endocrinology this week Gabriel Di Sante and colleagues from Philadelphia with the help of Canadian coworkers from Ottawa describe in mice another protein involved in this wandering of neurons. They found that the Sirt1 protein is necessary to start the migration of GnRH neurons. Sirt1 is the analogue of sirtuin protein originally found in yeast as Silent regulatory protein and has diverse physiological functions. Sirt1 defective mutants are not viable and die in utero.

The paper shows that the migration is initiated intracellularly due to the interaction of FGF8 and the FGF receptor, Sirt1, and corstatin, whereupon the sirtuin protein leaves the nucleus and deacylates the cytoplasmatically located corstatin. This interaction then makes the neuron migrate. There are other mechanisms listed in the introduction of the article which effect the migration. But none is as near to the origin of the migration as this one.

A nice piece of work! Recommended!