Scientists Discover Key to Regulation of Puberty

Researchers at the University of Cambridge and the University of Cukurova in Turkey have found the key in the brain that controls the onset of puberty.

Scientists found that Neurokinin B plays a critical role in controlling the system that switches on the master regulator of human puberty.

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Earlier, Neurokinin B was known to be present in the hypothalamus-the part of the brain that controls puberty.

But it's now that its role is identified and scientists believe that the finding 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.

Scientists knew 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. And switching on the system is essential to enter puberty and maintain sexual function in adults.

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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.

Thus, 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).

The mutations severely affect the function of Neurokinin B. The TAC3 gene codes for Neurokinin B while TACR3 produces its receptor.

The mutations were exclusively 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.

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The new study establishes that the central role for Neurokin B and its receptor in puberty and the regulation of sexual and reproductive function.

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.''

''''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,'' said Professor Steve O'Rahilly, from the University of Cambridge said.

The study is published in the latest issue of Nature Genetics.

Source-ANI
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