Over the past 150 years, the average onset of puberty has been steadily declining. A century and a half ago, girls reached reproductive competence around 17.5 years of age—but now, the average age is 12.5 years. Early-onset puberty can lead girls to experience health problems later, including increased incidence of ovarian, uterine and breast cancers, as well as being at a higher risk for cardiovascular and metabolic diseases.

Researchers at the Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU) and the Brigham & Women’s Hospital and Harvard Medical School, wondered what was causing this increase in early bloomers. Their research led to the discovery of a new gene (MKRN3) that serves as a “neurobiological brake”, that when mutated advances pubertal development. Children with mutations in the MKRN3 gene show signs of pubertal development as early as 5 years of age. Without this biological pause button, developing kids would be more susceptible to cancer, cardiovascular disease, and metabolic disorders.

“Developing our knowledge of how genes regulate the initiation of puberty will allow us understand why girls are initiating puberty at much earlier ages,” said Dr. Alejandro Lomniczi, lead researcher on the study and assistant professor for the Division of Neuroscience at the ONPRC.

Focusing on the hypothalamus, the ventral part of the brain that controls reproductive development, Lomniczi and colleagues demonstrated that in monkeys and rodents, the MKRN3 gene is highly expressed during infancy and gets shut down right before puberty. Using genetic and biochemical approaches they demonstrated that MKRN3 is a strong repressor of KISS1 and TAC3 gene expression, two strong activators of pubertal development.

With these discoveries guiding their work, researchers are starting to construct the genetic architecture that regulates reproductive development in the brain and one step closer of breaking the “puberty” code.

Updated: June 2020