Major success in international cooperation

Monday, 10 October, 2022

Erik Hrabovszky and Katalin Skrapits were invited by the French researcher leading the project to join the international team investigating a rare but serious congenital disorder. Their results offer hope for its treatment.


Science Translational Medicine is a journal with a very high impact factor (18), but no one from our institute has ever thought of publishing there. This first time is the result of an international collaboration. The invitation from the prestigious French research institute INSERM was due to the widely recognized excellent previous results of the team led by Erik Hrabovszky.


- Vincent Prévot, who is leading the research, indeed asked us to participate in a sub-project based on our previous work using a similar methodology. With Kata, we performed neuroanatomical studies on adult postmortem brains.

- You are investigating the bidirectional functional relationship between endocrine glands and the brain, with a particular focus on the role of GnRH (gonadotropin-releasing hormone).  How does this relate to the rare but severe disorder studied by Prévot and his group, congenital hypogonadotropic hypogonadism, which is often associated with anosmia (loss of sense of smell), hearing loss, and intellectual disability?

- The starting point for this work by Prévot's group was the observation that GnRH neurons born in the nasal placode also use nitric oxide (NO) signaling prior to their immigration to the brain. The study showed that this would later be critical for the establishment of intact reproductive functions.

- If the production of enzyme NO synthase in GnRH neurons is only transient, what role might this enzyme play in later sexual function? 

- Under normal individual development, the so-called "mini-puberty" in infants between 3-6 months of age is caused by transient activation of the reproductive axis. Work by Swiss co-authors has shown that NO signaling is critical in this process. A broader context is that impaired "mini-puberty" in preterm infants is often associated with adult fertility problems in which a defect in early NO signaling may also play a role. 

- What other results are reported in the publication?

- Hypogonadotropic hypogonadism caused by NO synthase deficiency was well reproduced in genetically modified animal models. The observation that early inhalation of NO in such animals prevented subsequent fertility problems was very exciting. Moreover, such treatment, at least in animal studies, could improve adult cognitive function!  

- I think everyone can guess what the next step is!

- In addition to the publication of the Science Translational Medicine article, Prévot's team has also launched a ground-breaking clinical collaboration to study the effects of inhaled NO treatment on premature infants. The significance of the publication and the clinical trial is summarised in layman's terms in the English-language press release

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