'Kevin and Perry' hormone

Behind the Headlines

Friday December 12 2008

Practical applications of the research are still many years away

Scientists have found “a ‘Kevin and Perry’ hormone that turns angelic children into foul-tempered teenagers”, the Daily Mail reported. It said a study has found that the hormone, neurokinin B, causes the hormonal surge in adolescence. The paper suggested that understanding the hormone better could lead to new contraceptives and treatments for sex hormone-fuelled diseases such as prostate cancer.

This study looked at mutations in two specific genes in four families with a rare hereditary form of hormone deficiency. People with the condition are prevented from having a normal progression to puberty.

This research is at a very early stage. If there are practical applications to come from it, such as new forms of contraception or treatments, they are many years away.

Where did the story come from?

Dr A Kemal Topaloglu and colleagues from Cukurova University along with universities in Turkey and Cambridge University in the UK carried out this research. The work was funded by grants from a number of sources including the Scientific and Technological Research Council of Turkey and the Wellcome Trust. It was published in the peer-reviewed medical journal Nature Genetics.

What kind of scientific study was this?

The researchers studied nine families, in which some members had a condition called normosmic idiopathic hypogonadotropic hypogonadism (nIHH). This condition is hereditary and involves a severe deficiency in the production of gonadotrophins, which prevents a normal progression to puberty.

Gonadotrophins are two hormones (luteinizing hormone and follicle-stimulating hormone) that come from the pituitary gland. They stimulate the gonads (male testes and female ovaries), and allow the production of male sex hormones including testosterone. Secretion of these male sex hormones is essential for the initiation of puberty, for maintaining male characteristics and for the normal development of male external genitalia, such as testes.

Nine families with nIHH were identified. The researchers report that although these families were not knowingly related to one another, they were consanguineous, meaning that some individuals had parents who were related to each other (e.g. first cousins). This makes the chance of hereditary disease in children more common.

The researchers then used a process known as genome-wide SNP analysis, which looks at the DNA sequence at specific points throughout an individual’s entire genetic make-up. The condition nIHH is recessive, which means that a person must carry two copies of the mutated gene (called being homozygous) in order to be affected. People who carry either one or no mutated copies of the gene are not affected. Therefore, the researchers looked for places in the genetic code where all of the affected people inherited two identical pieces of DNA (were homozygous), but unaffected people did not.

Through this, the researchers found a region on chromosome 4 that was homozygous in all six affected members of three of the families. This region included a gene calledTACR3 , which encodes a protein that binds to the protein neurokinin B (called a receptor). In another family, they identified a homozygous region in affected family members on chromosome 12 that included the TAC3 gene, which encodes the neurokinin B protein.

Although there were other genes within the regions identified, the researchers decided to concentrate on the TAC3 and TACR3 genes as they seemed likely to be the best candidates. This was partly because chemicals that affect the function of the neurokinin B receptor have been reported to affect reproductive function. Also, the neurokinin B receptor is found in the parts of the brain that control the release of gonadotrophins.

What were the results of the study?

The researchers found that some of the affected family members from three of the families had mutations in both copies of their TACR3 gene (were homozygous). The affected members of another family carried mutations in both copies of their TAC3 gene. None of the unaffected members of these families carried two mutated copies of either of these genes. The researchers did not identify mutations that might cause nIHH in five of the families they tested.

What interpretations did the researchers draw from these results?

The researchers say these findings suggest that neurokinin B is important in controlling the production of sex hormones in humans. They also say that their discovery suggests “new approaches to the pharmacological control of human reproduction and sex hormone-related diseases”, such as cancers of the breast and prostate.

What does the NHS Knowledge Service make of this study?

This study illustrates the potential of genome-wide SNP analysis in identifying the underlying mutation defects of a hereditary disease and in finding their precise location in the genetic code. Exactly how these genes affect the central control of reproduction remains to be established.

This research is at a very early stage. If there are any practical applications to come from it, such as new forms of contraception or treatments for diseases related to sex hormones such as prostate and breast cancer, they are still many years away.


Sir Muir Gray adds...

There's no easy answer yet for the parents of teenagers.


Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Kevin the Teenager created by a single hormone, scientists find. The Daily Telegraph, December 12 2008

Found: The 'Kevin and Perry' hormone that makes teens unbearable. Daily Mail, December 12 2008

Links to the science

Topaloglu AK, Reimann F, Guclu M, et al. TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. Nature Genetics 2008; published online December 11 2008


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