Sexual Precocity - Genetic Bases of Central Precocious Puberty and Autonomous Gonadal Activation.

Sexual Precocity - Genetic Bases of Central Precocious Puberty and Autonomous Gonadal Activation. Endocr Dev. 2016;29:50-71 Authors: Macedo DB, Silveira LF, Bessa DS, Brito VN, Latronico AC Abstract Precocious puberty has been classically defined as the onset of sexual secondary characteristics in girls younger than 8 years and in boys younger than 9 years. The discovery of potential factors which trigger human puberty is one of the central mysteries of reproductive biology. Several approaches, including mutational analysis of candidate genes, large-scale genome-wide association studies, and (more recently) whole-exome sequencing, have been performed in attempt to identify novel genetic factors that modulate the human hypothalamic-pituitary-gonadal axis, resulting in premature sexual development. In the last two decades, it has been well established that autonomous gonadal activation can be caused by somatic (GNAS) or germline (LHCGR)-activating mutations of genes that encode essential elements for signal transduction of G protein-coupled receptors, resulting in peripheral precocious puberty in McCune-Albright syndrome and testotoxicosis, respectively. More recently, dominant activating and inactivating mutations of excitatory (KISS1/KISS1R) and inhibitory (MKRN3) modulators of gonadotropin-releasing hormone secretion, respectively, were associated with central precocious puberty phenotype. Indeed, loss-of-function mutations of MKRN3...
Source: Endocrine Development - Category: Endocrinology Authors: Tags: Endocr Dev Source Type: research