Gene that unlocks puberty named 'Harry Potter' - ...

Summary:
Scientists at Paradigm Therapeutics, in following the company's practice of naming "orphan" genes -- those whose functions are unknown -- after famous orphans, have announced the gene they named Harry Potter appears to "trigger the cascade of hormones required for sexual reproduction."
The gene, now called GPR54] receives a hormone from the brain and triggers a complex biochemical process that leads eventually to production of sex steroids from the testes and ovaries.

"As it turned out, Peter Pan would have been a better name," said Dr. Samuel Aparicio, chief scientist of Paradigm. Mice in which the Harry Potter gene was inactivated failed to undergo the sexual maturation that normally occurs at puberty.



Article:

A transatlantic research collaboration has identified a gene that plays a key role in regulating the onset of puberty, one of the great mysteries of human biology.


The discovery could lead to new infertility treatments, contraceptives and even cancer drugs.

The gene, called GPR54, makes a protein that appears to trigger the cascade of hormones required for sexual reproduction.

It was discovered through a combination of mouse research by Paradigm Therapeutics, a British biotechnology company based in the English city of Cambridge, and human genetic analysis by scientists at Massachusetts General Hospital in Boston.

"It looks like we have found a key genetic gatekeeper of puberty in mice and men," said William Crowley, chief of the Reproductive Endocrine Unit at Massachusetts General. "Most other genes involved in reproductive control are species-specific, but this gene shows robust activity across two very different mammalian species."

GPR54 is a "receptor protein", a molecular docking station on the cell surface.

It receives a hormone from the brain and triggers a complex biochemical process that leads eventually to production of sex steroids from the testes and ovaries.

The discovery was published yesterday in the New England Journal of Medicine.

The most obvious application of GPR54 is as a drug target for treating hormonal disorders in which puberty occurs abnormally early or late.

But Samuel Aparicio, chief scientist of Paradigm, said it might also be useful for controlling fertility in adults - it could lead to new contraceptives for men and women - and for reducing hormone production in patients with hormone-dependent cancers, for example of the breast or prostate.

Paradigm investigated GPR54 as part of its programme of genetically manipulating mice to study "orphan" genes whose function is not yet known.

At this early stage it was called Harry Potter, in keeping with the company's practice of naming orphan genes after famous orphans.

"As it turned out, Peter Pan would have been a better name," Dr Aparicio said. Mice in which the Harry Potter gene was inactivated failed to undergo the sexual maturation that normally occurs at puberty.

At the same time the scientists at Massachusetts General were independently investigating the genetics of a human disorder called idiopathic hypogonadotropic hypogonadism, in which puberty does not occur at the usual age.

By studying an extended family from Saudi Arabia in which both girls and boys failed to undergo puberty, they discovered that the gene responsible was GPR54 on chromosome 19.

The two research teams then got together, pooled their results and confirmed that Harry Potter in mice and GPR54 in people were the same in structure and function.

They note that it is not the only gene whose action is required for the onset of puberty but rather one of an ensemble of genes in charge of a complex process.

Environmental factors play a role too - better childhood nutrition has pushed forward the date of puberty in the industrialised world over the past century


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