1.Use of Gonadotropin-Releasing Hormone for Intractable Seizures in a Girl with Precocious Puberty without Hypothalamic Hamartoma.
Govil-Dalela T1, Kumar A2, Moltz KC3, Chugani HT4. J Pediatr. 2016 May 4. pii: S0022-3476(16)30022-1. doi: 10.1016/j.jpeds.2016.03.078. [Epub ahead of print]
The use of gonadotropin-releasing hormone analogs has been reported in the treatment of gelastic seizures and precocious puberty associated with hypothalamic hamartomas, but not in other seizure types without hypothalamic hamartoma. We describe a 7.5 year-old girl whose seizures subsided after gonadotropin-releasing hormone analog implant, administered for precocious puberty.
2.IGSF10 mutations dysregulate gonadotropin-releasing hormone neuronal migration resulting in delayed puberty.
Howard SR1, Guasti L1, Ruiz-Babot G1, Mancini A1, David A2, Storr HL1, Metherell LA1, Sternberg MJ2, Cabrera CP3, Warren HR4, Barnes MR3, Quinton R5, de Roux N6, Young J7, Guiochon-Mantel A8, Wehkalampi K9, André V10, Gothilf Y11, Cariboni A12, Dunkel L13. EMBO Mol Med. 2016 Apr 13. pii: e201606250. doi: 10.15252/emmm.201606250. [Epub ahead of print]
Early or late pubertal onset affects up to 5% of adolescents and is associated with adverse health and psychosocial outcomes. Self-limited delayed puberty (DP) segregates predominantly in an autosomal dominant pattern, but the underlying genetic background is unknown. Using exome and candidate gene sequencing, we have identified rare mutations in IGSF10 in 6 unrelated families, which resulted in intracellular retention with failure in the secretion of mutant proteins. IGSF10 mRNA was strongly expressed in embryonic nasal mesenchyme, during gonadotropin-releasing hormone (GnRH) neuronal migration to the hypothalamus. IGSF10 knockdown caused a reduced migration of immature GnRH neurons in vitro, and perturbed migration and extension of GnRH neurons in a gnrh3:EGFP zebrafish model. Additionally, loss-of-function mutations in IGSF10 were identified in hypothalamic amenorrhea patients. Our evidence strongly suggests that mutations in IGSF10 cause DP in humans, and points to a common genetic basis for conditions of functional hypogonadotropic hypogonadism (HH).
3.The expression of several reproductive hormone receptors can be modified by perfluorooctane sulfonate (PFOS) in adult male rats.
López-Doval S1, Salgado R1, Lafuente A2. Chemosphere. 2016 May 2;155:488-497. doi: 10.1016/j.chemosphere.2016.04.081. [Epub ahead of print]
This study was undertaken to evaluate the possible role of several reproductive hormone receptors on the disruption of the hypothalamic-pituitary-testis (HPT) axis activity induced by perfluorooctane sulfonate (PFOS). The studied receptors are the gonadotropin-releasing hormone receptor (GnRHr), luteinizing hormone receptor (LHr), follicle-stimulating hormone receptor (FSHr), and the androgen receptor (Ar). Adult male rats were orally treated with 1.0; 3.0 and 6.0 mg of PFOS kg-1 d-1 for 28 days. In general terms, PFOS can modify the relative gene and protein expressions of these receptors in several tissues of the reproductive axis. At the testicular level, apart from the expected inhibition of both gene and protein expressions of FSHr and Ar, PFOS also stimulates the GnRHr protein and the LHr gene expression. The receptors of the main hormones involved in the HPT axis may have an important role in the disruption exerted by PFOS on this axis.
