Endocrine Abstracts

Attainment of mammalian reproductive capacity depends on an increased pulsatile release of gonadotropin releasing hormone (GnRH) from hypothalamus neurons. After reaching the pituitary gland GnRH stimulates the synthesis and release of gonadotropins, which in turn promote gonadal function. The pubertal activation of GnRH secretion is brought about by coordinated changes in transsynaptic and glial-neuronal communication, which involve an increase in neuronal and glial excitatory inputs to the GnRH neuronal network and a decrease in transsynaptic inhibitory influences. Coordination of this regulatory neuronal-glial network appears to require gene networks hierarchically arranged. One level of coordination is provided by subordinate genes encoding proteins required for dynamic cell–cell communication. A second level is provided by subordinate genes engaged in intracellular signaling. A third and higher level of control involves the transcriptional regulation of these genes by a handful of genes that acting as ‘central nodes’ sustain the functional integration of the network. The existence of functionally connected genes controlling the pubertal process is consistent with the concept that puberty is under genetic control, and that the genetic underpinnings of both normal and deranged puberty are polygenic rather than specified by a single gene. It is unclear, however, how such inherited, permanent changes in DNA sequence can dynamically coordinate the expression of gene sets controlling the pubertal process. Using high-throughput approaches and computational methods for global analysis of DNA methylation and chromatin modifications, as well as quantification of mRNA and protein expression, we have obtained evidence suggesting that the activity of gene networks controlling puberty is coordinated by an epigenetic mechanism of transcriptional repression, which prevent the premature unfolding of the pubertal process.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.