The effect of dapsone in testosterone enanthate-induced polycystic ovary syndrome in rat.

BACKGROUND: One of the most common reasons for infertility is polycystic ovary syndrome (PCOS). PCOS is related to metabolic syndrome, weight gain, type 2 diabetes mellitus, and cardiovascular diseases. Some of the causes of PCOS are dysfunction in the hypothalamus-pituitary-ovarian axis, insulin activity as well as over-activity of sympathetic nerves and elevation in serum levels of pro-inflammatory cytokines. Dapsone, a sulfonamide antibacterial agent, has anti-inflammatory effects such as decreasing inflammatory cytokine levels like TNF-α and IL-1ß. METHODS: PCOS was induced by subcutaneous injection of testosterone enanthate (1 mg/100 g) in 21 days old female rats for 35 days. Then, the MET control received metformin (300 mg/kg/day, orally) for 28 days, and to evaluate the efficacy of dapsone (DAP), the DAP group received (12.5 mg/kg, orally) for 28 days. Then, on the last day of the study, the rats were euthanized and the blood was collected to measure the serum levels of hormones, glucose, LDL, LDL/HDL and the left ovaries were dissected for histopathological assay. RESULTS: In the PCOS group, the serum levels of glucose, LDL and LDL/HDL were significantly higher than in the control group (P < 0.001). In addition, the levels of LH, FSH and testosterone changed in the PCOS group compared to the control (P < 0.001). The histopathological morphology changes of the ovary of the PCOS group were significant. Treatment with dapsone and metformin reversed the effects of testosterone in the DAP and MET groups. CONCLUSIONS: Based on the data, dapsone displayed a good antiandrogenic role via decreasing the testosterone levels in PCOS-induced rats.

The effect of adrenocorticotropic hormone on alpha-2-macroglobulin in osteoblasts derived from human mesenchymal stem cells.

Nowadays, alpha-2-macroglobulin (A2M) gene has allocated escalating interest among several genes involved in the pathogenesis of avascular necrosis of the femoral head (ANFH). This molecule could interact with several osteogenic-related proteins. It was reported that adrenocorticotropic hormone (ACTH) affects bones through its receptor located on osteoblasts, suggesting it as a potential target in ANFH treatment. In this study, the effect of ACTH on A2M expression was investigated in osteoblasts as well as during the differentiation of human mesenchymal stem cells (MSCs) into osteoblasts. In this study, MSCs derived from bone marrow were isolated and purified using Ficoll gradient and several passaging. MSCs were characterized by induction with osteogenic and adipogenic medium followed by Oil Red O, Alizarin Red and alkaline phosphatase staining. Besides, MSCs were exposed to various concentrations of ACTH to evaluate the cell variability by MTT assay. MSCs and differentiated osteoblasts were treated with 10-8 molar ACTH for 16 and 26 days, respectively. Then, the total RNA was extracted and A2M expression was quantified by real-time qPCR. The protein expression levels of osteoblast markers including alkaline phosphatase (ALPL) and bone gamma-carboxyglutamate protein (BGLAP) were also measured. The results showed that A2M expression in cells treated with ACTH was up-regulated significantly compared to the control group. Similarly, the expression of osteoblast gene markers including ALPL and BGLAP was significantly increased. ACTH, as an osteoblastic differentiation enhancer, up-regulates A2M, which promotes osteoblastic differentiation probably through TGF-ß induction.