Key to regulation of puberty discovered

December 11, 2008,

A team of scientists from the University of Cambridge and the University of Cukurova in Turkey have taken a major step to understanding how the brain controls the onset of puberty.

The research, published in this week's Nature Genetics, identified the hormone Neurokinin B as a critical part of the control system that switches on the master regulator of human puberty. Although Neurokinin B was previously known to be present in the hypothalamus, the part of the brain that controls puberty, its key role was not previously appreciated.

The identification of Neurokin B could lead to new treatments for sex hormone dependent diseases like prostate cancer, new approaches to contraception, and its manipulation could result in new treatments for children with delayed or abnormal puberty.

It has long been known that a specific hormonal signal from the hypothalamus is essential to switch on the system that controls the production of sex hormones from the ovaries and testis. Turning on the system is essential to enter puberty and maintain sexual function in adults.

Control over this system is governed by the brain through the release of the hormone GnRH (gonadotroopin releasing hormone) which starts a series of processes that ultimately leads to the production of sex hormones. However how GnRH secretion is turned off after birth, and how it reactivates at puberty, has been unclear.

In order to identify new signals involved in regulating this process, the researchers used a strategy of searching for genetic defects in families in Turkey in which more than one member did not go through puberty, making an inherited defect likely. They discovered mutation in two genes: TAC3 (one family) and TACR3 (three families).

Mutations in these genes severely affect the function of Neurokinin B. The TAC3 gene codes for Neurokinin B while TACR3 produces its receptor. These mutations were only found in members with the condition, severe congenital gonadotropin deficiency, and not their siblings. Affected individuals were all homozygous (they have two identical copies of the gene) for these mutations.

A small number of studies using mice and rats had previously linked Neurokinin B to puberty, but the wider view was that its main role was instead in water balance, cognitive function or a number of other processes. This research clears this uncertainty and establishes the central role for Neurokin B and its receptor in puberty and the regulation of sexual and reproductive function.

Commenting on the research Dr Robert Semple, from the University of Cambridge and one of the authors of the study said: "As a practicing doctor I am excited by this discovery because it immediately helps to understand the underlying problem in rare patients with inherited defects in sexual maturation, and suggests a potential target for their specific treatment. However identifying single genetic defects in patients with rare disorders also has implications for understanding normal regulation of key bodily functions, and is one of the most powerful ways of proving the genes concerned.

"The neurokinin B/neurokinin 3 receptor system is highly amenable in principle to targeting as a treatment, and I expect that this genetic discovery will lead to intense efforts to understand neurokin B's role in puberty in more detail, and to try to develop clinically valuable drugs."

Professor Steve O'Rahilly, from the University of Cambridge said: "This unexpected finding puts one more important piece in the unfinished jigsaw puzzle that is our understanding of puberty. It could also open up new ways of treating certain sex hormone related diseases."

Article: The article 'TAC3 and TACR3 Mutations in Familial Hypogonadotropic Hypogonadism Reveal a Key Role for Neurokinin B in the Central Control of Reproduction' will appear in the online edition of Nature Genetics on 12 December.

Source: University of Cambridge

Related Stories

Recommended for you

Variants in non-coding DNA contribute to inherited autism risk

April 19, 2018
In recent years, researchers have firmly established that gene mutations appearing for the first time, called de novo mutations, contribute to approximately one-third of cases of autism spectrum disorder (ASD). In a new study, ...

Researchers discover link between gene variation and language

April 18, 2018
What shapes the basic features of a language?

Natural selection still at work in humans

April 18, 2018
Evolution has shaped the human race, with University of Queensland researchers finding signatures of natural selection in the genome that influence traits associated with fertility and heart function.

Gene therapy for beta-thalassemia safe, effective in people

April 18, 2018
In a powerful example of bench-to-bedside science showing how observations made in the lab can spark life-altering therapies in clinic, an international team of clinician-investigators has announced that gene therapy for ...

Potential lines of attack against prostate cancer

April 17, 2018
Researchers from The University of East Anglia (UEA) have contributed to the world's largest study into genes that drive prostate cancer – identifying 80 molecular weaknesses that could be targeted by drugs to treat the ...

Epstein-Barr virus linked to seven serious diseases

April 16, 2018
A far-reaching study conducted by scientists at Cincinnati Children's reports that the Epstein-Barr virus (EBV)—best known for causing mononucleosis—also increases the risks for some people of developing seven other major ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Dec 16, 2008
Why won't physorg remove these people spamming the comments with adds?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.