The timing of the onset of puberty is linked to levels of nutrition: later onset is associated with malnutrition, while earlier onset is linked to childhood obesity. A team of researchers, led by Carol Elias, at the University of Texas Southwestern Medical Center, Dallas, has now generated data in mice that run counter to current thinking about the molecular pathway by which nutrition status affects the onset of puberty. Further, the team defines a new regulatory pathway for the process, which, if confirmed in humans, could potentially lead to new approaches to treating disorders of puberty and fertility.
The hormone leptin, which is produced by fat tissue, is a key signal that lets the reproductive system know that levels of nutrition are sufficient to support puberty. Several lines of data had led researchers to believe that the permissive effects of leptin on puberty were mediated indirectly, by leptin stimulating nerve cells in a region of the brain known as the hypothalamus to produce kisspeptins, small proteins that trigger the first step in the onset of puberty.
However, Elias and colleagues, found no effects on puberty in mice when expression of the molecule to which leptin binds was selectively eliminated in kisspeptin-producing nerve cells in the hypothalamus. Further analysis revealed that expression of the molecule to which leptin binds in a region of the brain known as the ventral premammillary nucleus was required for leptin to exert its effects on puberty onset.
In an accompanying commentary, Rexford Ahima, at the University of Pennsylvania, Philadelphia, notes that the comprehensive series of experiments carried out by Elias and colleagues provide important new insight into the regulation of puberty onset that could potentially have clinical ramifications.
TITLE: Leptin’s effect on puberty in mice is relayed by the ventral premammillary nucleus and does not require signaling in Kiss1 neurons
Carol F. Elias
University of Texas Southwestern Medical Center, Dallas, Texas, USA.
View this article at: http://www.jci.org/articles/view/45106?key=0ba657de2e2d16c52134
TITLE: No Kiss1ng by leptin during puberty?
Rexford S. Ahima
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Contact: Karen Honey
Journal of Clinical Investigation