Two molecules that work together to help set up the sense of smell and pave the way to puberty in mice have been identified by researchers. The new findings by neuroscientists led by Professor Christiana Ruhrberg from the University College London in the UK and Professor Anna Cariboni from the University of Milan in Italy may help understand why patients with the inherited condition Kallmann syndrome cannot smell properly and cannot start puberty without hormone treatment.
According to the US National Library of Medicines, Kallmann syndrome, characterized by delayed or absent puberty and an impaired sense of smell, is a form of hypogonadotropic hypogonadism resulting from a lack of production of certain hormones made in the hypothalamus that direct sexual development.
According to the researchers, PLXNA1 and PLXNA3 molecules present in nerves that extend from the nose into the brain of developing mice might be linked to Kallmann syndrome. The researchers found these nerves transmit signals essential for the sense of smell and also guide hormone-secreting nerve cells from their place of origin in the nose to their destination in the brain, where they regulate the onset of puberty.
The disorder that affected "Little" Jimmy Scott, who naturally had a high singing voice due to Kallmann syndrome, is diagnosed in one in 30,000 males and one in 120,000 females. Due to the lack of a hormone that stimulates the brain to produce signals needed to reach sexual maturity, people with the condition do not go through puberty and instead retain a child-like stature, no sex drive, no sense of smell, and underdeveloped genitals.
People suffering from the disorder are treated by hormone-replacement therapy to bypass the brain and kick-start puberty. The study published in journal Development Biology revealed that both types of nerves were not wired properly when PLXNA1 and PLXNA3 absent in developing mice, resulting in the poor formation of brain regions that process smell and the lack of puberty-promoting nerve cells in the brain.
"By studying the mouse as a model organism, we have identified a pair of genes that can cause an inherited condition with symptoms similar to Kallmann. This is an important finding because the nerves that convey our sense of smell and that guide the puberty-inducing nerve cells arise in a very similar way during the development of mice and humans whilst they are still in the womb," explained author Professor Christiana Ruhrberg.
Co-author Professor Anna Cariboni said knowing the underlying genetic causes of Kallmann syndrome could make a huge difference to speed up diagnosis and give treatment to the right patients at an earlier time.