Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes.

Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH. Materials and methods: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. Results: We identified 12 possible pathogenic variants in GHRHR, GH1, GLI2, PROP-1, POU1F1, and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR, two in POU1F1, one in GLI2, and one in LHX4. In all patients, these variants were most frequently found in GLI2, followed by PROP-1 and GHRHR. Conclusion: Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH.

Oxytocin alleviates cisplatin-induced renal damage in rats.

OBJECTIVES: The purpose of the present study was to investigate the protective effect of oxytocin on cisplatin (CP)-induced renal damage in rats. MATERIALS AND METHODS: Fourteen adult Sprague Dawley rats, weighing 200 to 210, were administered by cisplatin (CP, 2 mg/kg/day) twice a week for five weeks. Then, they were randomly divided into two groups and treated with either saline (1 ml/kg/day) or OT (200 µg/kg/day) for five weeks. Seven rats served as control group. At the end of the treatment period, animals were sacrificed and their kidneys were assessed histologically. In addition, C-reactive protein (CRP), TGF-ß and Akt expression were evaluated immunohistochemically. RESULTS: Both tubules and glomeruli were found to be severely damaged with marked medullary tubulo-interstitial inflammation due to chronic cisplatin exposure, particularly in the salinetreated group (Group 1) compared to control group. Oxytocin treatment spared renal-tissue significantly by suppressing CRP and TGF-ß , and enhancing Akt expression. CONCLUSION: We conclude that renal damage due to cisplatin toxicity was prevented to a great extent by the anti-inflammatory effect of oxytocin.