Hypothalamic hamartoma: a paradigm/model for studying the onset of puberty.

This article discusses the potential mechanisms by which hypothalamic hamartomas (HHs) are formed and cause precocious puberty. The hypothesis is presented suggesting that HHs accelerate sexual development by producing bioactive substances that mimic - in an accelerated time-course - the cascade of events underlying the normal initiation of puberty. It is also proposed that because HHs contain key transcriptional and signaling networks required to initiate and sustain a pubertal mode of gonadotropin-releasing hormone (GnRH) release, they are able to trigger the pubertal process at an earlier age. The cellular components of this activating complex may include: (a) neurons able to produce GnRH within the HH: (b) controlling neurons synaptically connected to GnRH neurons in the HH itself and/or to neuronal networks (including GnRH neurons) in the patient's hypothalamus, and (c) signaling-competent astrocytic and ependymoglial cells. It is also possible that the developmental abnormalities leading to the formation of HHs result from sporadic defects affecting the same genes and hence the same morphogenic pathways involved in the embryonic development of the ventral hypothalamus and the floor of the third ventricle.