Discordance in the Dependence on Kisspeptin Signaling in Mini Puberty vs. Adolescent Puberty: Human Genetic Evidence.
J Clin Endocrinol Metab. 2018 Feb 14;:
Authors: Shahab M, Lippincott M, Chan YM, Davies A, Merino PM, Plummer L, Mericq V, Seminara S
Abstract
Context: Hypothalamic kisspeptin signaling plays a critical role in the initiation and maintenance of reproductive function. Biallelic mutations in the coding sequence of KISS1R (GPR54) have been identified in patients with idiopathic hypogonadotropic hypogonadism (IHH), but it is unknown whether biallelic variants can also be associated with related reproductive disorders.
Case description: A missense homozygous variant (c.890G>T p.R297L) in KISS1R was identified in a child who presented with microphallus and bilateral cryptorchidism. This variant has been previously reported to reduce, but not abolish, post-receptor signaling in vitro. Biochemical evaluation during the neonatal period revealed low testosterone. By 11 years 8 months, the boy began demonstrating increases in testicular volume. By 17 years 3 months, his testicular volume was 20 cc; his penile length was 7.3 cm; and he had adult levels of circulating gonadotropins and testosterone.
Conclusion: This is the first association of biallelic loss-of-function mutations in KISS1R with normal timing of adolescent puberty. Moreover, because these coding sequence variants occurred in a subject with microphallus and cryptorchidism, they demonstrate different levels of dependence of the hypothalamic-pituitary-gonadal cascade on kisspeptin signaling at distinct times in the reproductive life span. The suppression of the hypothalamic-pituitary-gonadal cascade during early life but not adolescence suggests that the mini puberty of infancy is more dependent upon kisspeptin-induced, GnRH-induced LH secretion than adolescent puberty.
PMID: 29452377 [PubMed - as supplied by publisher]
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