NEW YORK (Reuters Health) - An intact G protein-coupled receptor gene (GPR54) seems to be necessary for normal puberty to occur in both humans and mice, according to a report published in the October 23rd issue of The New England Journal of Medicine.

This gene could represent a new target for drugs designed to treat abnormal puberty and hormone-dependent cancers.

"It looks like we have found a key genetic gatekeeper of puberty in mice and men," senior author Dr. William Crowley, Jr., from Massachusetts General Hospital in Boston, said in a statement. "Most other genes involved in reproductive control are species-specific, but this gene shows robust activity across two very different mammalian species."

Using linkage analysis and candidate-gene screening, the researchers were able to identify GPR54 mutations in patients with idiopathic hypogonadotropic hypogonadism (IHH), an uncommon disorder in which pubertal development is lacking. In addition, they were able to create GPR54-deficient mice that mimicked humans with IHH.

Further analysis revealed that both copies of GPR54 needed to have mutations for IHH to occur. However, these mutations did not need to be the same ones, the authors point out.

In the knockout mice, gonadotropin-releasing hormone (GnRH) levels in the hypothalamus were normal. Moreover, such animals were able to respond to exogenous gonadotropins and GnRH.

Exactly how the GPR54 mutations lead to pubertal delay remains to be determined, the authors note. Furthermore, such mutations are not found in most cases of IHH, they add.

"The normal hypothalamic content of GnRH peptide in the knockout model argues that these neurosecretory neurons are present in the hypothalamus and can synthesize this peptide," Dr. David R. Beier and Dr. Robert G. Dluhy, from Harvard Medical School in Boston, note in a related editorial.

"Thus, it is likely--but still unproven--that GPR54 regulates the processing or secretion of GnRH by the hypothalamus," they add.

N Engl J Med 2003;349:1589-1592,1614-1627.

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