"Using a mouse model, our lab has determined that the absence in the brain's hypothalamus of a gene called TTF-1 causes a delay in the onset of female puberty," explained Ojeda. "This work is of particular interest to those investigating both the delay and early onset of puberty in young women. While there is no definitive information, recently a number of research papers have been published suggesting that young women are reaching puberty at an earlier age. Other research has suggested that if this is the case, it may be linked to the nation's obesity crisis."
Prior to the research to be reported at the Society for Neuroscience meeting, Ojeda's group performed studies with rats showing that the TTF-1 gene is expressed in a discrete cellular subset of the hypothalamus during sexual development. Then, using a genome-wide approach, they determined that expression of the TTF-1 gene increases in the hypothalamus of nonhuman primates at the onset of puberty.
To conduct this latest research, Ojeda and his colleagues teamed up with Shioko Kimura, Ph.D., at the National Institute of Health's National Cancer Institute to study mice in which the TTF-1 gene had been deleted selectively from neurons. They then tracked development of these animals in comparison with a control group of wild-type littermate mice. The researchers found that animals lacking this gene exhibited delayed puberty. The mice lacking TTF-1 also had fewer litters, had fewer pups in each litter, and their reproductive time span was half that of a normal animal.
Ojeda and his colleagues now are tracking other genes that might interact with TTF-1 in the brain to control the onset of puberty.
"While observational studies are required to determine the role of TTF-1 in humans, we know that children recently described to have mutations of this gene suffer from loss of motor coordination and alterations in fluid balance," said Ojeda. "It will be important to continue observing these patients to determine whether they also witness a delay in the onset of puberty."
OHSU includes the schools of dentistry, medicine, nursing and science and engineering; OHSU Hospital and Doernbecher Children's Hospital; numerous primary care and specialty clinics; multiple research institutes; and several outreach and community service units.
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