The onset of puberty is a critical developmental milestone regulated by complex neuroendocrine networks that integrate genetic, metabolic, and environmental cues. Among the molecular systems coordinat Show more
The onset of puberty is a critical developmental milestone regulated by complex neuroendocrine networks that integrate genetic, metabolic, and environmental cues. Among the molecular systems coordinating this transition, neurotrophins-including brain-derived neurotrophic factor (BDNF), nerve growth factor, neurotrophin-3, and neurotrophin-4/5-have emerged as important modulators of hypothalamic maturation and the activation of gonadotropin-releasing hormone (GnRH) neurons. Beyond their established roles in neuronal survival and differentiation, neurotrophins contribute to hypothalamic circuit plasticity, influence GnRH neuronal activity, and participate in the integration of metabolic and environmental signals relevant to reproductive maturation. Experimental studies, primarily based on animal and cellular models, demonstrate that BDNF and its receptor play a role in normal pubertal onset, whereas disruptions in neurotrophin signaling have been implicated in central precocious puberty, delayed puberty, and hypogonadotropic hypogonadism. In humans, available evidence is more limited and derives mainly from genetic studies, circulating neurotrophin measurements, and clinical observations. This review provides an integrative synthesis of current experimental and clinical data on neurotrophin-mediated regulation of pubertal timing, highlighting both physiological mechanisms and pathological conditions. While neurotrophins represent promising modulators at the intersection of neurodevelopment, metabolism, and reproduction, further longitudinal and translational human studies are required to define their diagnostic and therapeutic potential in pediatric endocrinology. Show less
Pena-Shokeir syndrome type I is a rare genetic disorder that includes multiple congenital facial and joint anomalies as well as pulmonary hypoplasia. Affected infants are usually premature, and 30% of Show more
Pena-Shokeir syndrome type I is a rare genetic disorder that includes multiple congenital facial and joint anomalies as well as pulmonary hypoplasia. Affected infants are usually premature, and 30% of them are stillborn. So far, studies have reported low-set ears in such infants, with no middle or inner ear findings. Histopathological study of human temporal bones with Pena-Shokeir syndrome type I. Our case report describes an infant with severely decreased number of spiral ganglion cells and number of outer and inner hair cells of the cochlea, mild loss of vestibular hair cells, hypoplasia in the facial nerves, and ischemic degeneration of Schwann cells in the modiolus. Pena-Shokeir syndrome type I is associated with a degenerative process in the labyrinth. Show less