Anti-hyperprolactinemia mechanism of Radix bupleuri extract in rats

Purpose: To determine the mechanism underlying the anti-hyperprolactinemia effects of Radix bupleuri extract (RBE) in rats. Methods: Rats were divided into six groups (n=10 each group): healthy controls, untreated hyperprolactinemic rats, hyperprolactinemic rats treated with bromocriptine (0.6 mg/kg), and hyperprolactinemic rats treated with RBE (4.8, 9.6, or 19.2 g/kg). After 30 days, hypothalamic protein levels of dopamine D2 receptor, protein kinase A (PKA), and cyclic adenosine monophosphate (cAMP) were determined. Results: Dopamine D2 receptor levels were lower in untreated hyperprolactinemic rats than in healthy controls (p < 0.01), but this decrease was attenuated by RBE (p < 0.05). Elevated PKA levels in untreated hyperprolactinemic rats (0.61 ± 0.04 μg/ml, p < 0.01) were decreased by RBE (4.8 g/kg, 0.42 ± 0.03 μg/ml, p < 0.05; 9.6 g/kg, 0.33 ± 0.02 μg/ml, p < 0.01; 19.2 g/kg, 0.27 ± 0.03 μg/ml, p < 0.01). Similarly, elevated cAMP levels in hyperprolactinemic rats (2.4 ± 0.4 ng/ml) were decreased by RBE (4.8 g/kg, 1.8 ± 0.3 ng/ml, p < 0.05; 9.6 g/kg, 1.5 ± 0.3 ng/ml, p < 0.01; 19.2 g/kg, 1.2 ± 0.2 ng/ml, p < 0.01). Conclusions: RBE anti-hyperprolactinemia activity is mediated by dopamine D2 receptor signaling via the cAMP/PKA pathway.

Molecular analysis of exons 8, 9 and 10 of the fibroblast growth factor receptor 2 (FGFR2) gene in two families with index cases of Apert Syndrome

Introduction: Apert syndrome (AS) is a craniosynostosis condition caused by mutations in the Fibroblast Growth Factor Receptor 2 (FGFR2) gene. Clinical features include cutaneous and osseous symmetric syndactily in hands and feet, with variable presentations in bones, brain, skin and other internal organs. Methods: Members of two families with an index case of Apert Syndrome were assessed to describe relevant clinical features and molecular analysis (sequencing and amplification) of exons 8, 9 and 10 of FGFR2 gen. Results: Family 1 consists of the mother, the index case and half -brother who has a cleft lip and palate. In this family we found a single FGFR2 mutation, S252W, in the sequence of exon 8. Although mutations were not found in the study of the patient affected with cleft lip and palate, it is known that these diseases share signaling pathways, allowing suspected alterations in shared genes. In the patient of family 2, we found a sequence variant T78.501A located near the splicing site, which could interfere in this process, and consequently with the protein function.