Endocrine Abstracts

During the infantile-pubertal transition, a diversity of behavioral, physiological, morphological and molecular changes are required in order to attain fertility. An essential step in this process is the reactivation of the pituitary-gonadal axis by increased hypothalamic secretion of Gonadotropin-Releasing Hormone (GnRH). This drives the adenohypophysis to increase the pulsatile release of luteinizing hormone (LH) with diurnal periodicity, the first endocrine sign of pubertal development. The current dogma postulates that diminishing transsynaptic inhibition jointly with increased excitatory inputs is responsible for the reactivation of GnRH release. With the advent of new high throughput genomic technologies today we can interrogate the developing hypothalamus for genome-wide changes in mRNA expression as well as epigenetic modifications associated with gene regulatory/promoter regions. Over the last several years, a plethora of new transcriptional complexes, some of which with epigenetic capabilities have been found to be involved in the hypothalamic control of pubertal development. Here, we will review the contribution of several families of epigenetic writers, readers, and erasers in the shift from a repressive to an activated chromatin state at promoter and enhancer regions of the Kiss1 gene during the infantile-pubertal transition. This relatively new mode of epigenetic regulation opens up to the exciting possibility that the reactivation of the GnRH pulse generator lays in the genetic/epigenetic architecture of the Kiss neuron. In addition, we will discuss the tantalizing possibility that epigenetics serves as a relay of environmental signals known for many years to modulate pubertal development.