Scientists Find a Gene That Is Key to Puberty
Scientists have discovered a gene that is crucial for the onset of puberty, a human developmental process that has long been swathed in mystery.
The finding, published today in the New England Journal of Medicine, should deepen scientists’ and doctors’ understanding of the chemical triggers that cause the body to sexually mature and also shed light on the reasons for puberty arriving abnormally early or late.
“One of the challenges a pediatrician faces is looking at a child who is delayed in puberty and trying to determine if this child is going to be OK and kick spontaneously into their own pubertal development or if he or she has a bigger problem,” said Dr. Stephanie Seminara, a reproductive endocrinologist at Massachusetts General Hospital in Boston, a Harvard University professor and a lead author on the study. A better understanding of the genes and physiology underlying puberty may aid in diagnoses and perhaps provide ideas for novel therapies, she said.
A team of French scientists independently reported on the gene’s role in puberty in a paper first published online in August in the Proceedings of the National Academy of Sciences.
Puberty begins when the brain’s hypothalamus begins secreting a hormone -- gonadotropin-releasing hormone, or GnRH -- in an elaborate pattern of pulses. In response, the pituitary gland secretes additional hormones, which act on the ovaries and testes. They, in turn, induce the growth of breasts, body hair and other signs of sexual maturity.
However, endocrinologists don’t understand what triggers the GnRH pulses that set the whole cascade in motion.
To tackle the problem, the Boston researchers teamed with a Kuwaiti physician to study a Saudi Arabian family with a rare genetic disorder known as idiopathic hypogonadotropic hypogonadism.
Children affected by this condition never enter puberty unless doctors treat them with pulses of GnRH. Using DNA from family members, the scientists discovered that a gene causing the condition lay in chromosome number 19.
The team was then approached by scientists at a British biotechnology company, Paradigm Therapeutics, and Cambridge University. They had created mice that lacked one of the chromosome 19 genes, known as GPR54, producing mice that never matured sexually.
The researchers then analyzed the Saudi family’s DNA, and discovered that those affected by the disorder carried a damaged, malfunctioning version of GPR54.
However, the authors noted that this genetic defect is not the only cause of idiopathic hypogonadotropic hypogonadism. Many families with this condition carry normal GPR54 genes and therefore must have problems in other genes.
Seminara said the goal now is to understand GPR54’s function. The scientists know it is the blueprint for a protein receptor that is actively made in the hypothalamus during puberty. They suspect it plays a crucial role in releasing GnRH from the hypothalamus so it can begin its pulsing job.
