Effects of vitamin D on steroidogenesis, reactive oxygen species production, and enzymatic antioxidant defense in human granulosa cells of normal and polycystic ovaries.

Polycystic ovary syndrome (PCOS) is accompanied with many disturbances in hormone synthesis and antioxidant defense. Previous reports have indicated that Vitamin D (vit.D) affects gene expression and have roles in normal follicular development. Therefore, we investigated the effects of vit.D on steroidogenesis, apoptosis, reactive oxygen species (ROS) production, and antioxidant defenses of human normal granulosa cells (N-GCs) and granulosa cells from polycystic ovaries (PCO-GCs). Ovarian GCs were obtained during oocyte retrieval procedure from 120 women with PCOS and from 100 healthy women who referred to Shiraz Fertility Center. The isolated GCs were cultured in the presence or absence of vit.D (100 nM), for 48 h. Concentration of sex steroids was measured by ELISA. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) expression and activities were assessed by q-PCR and photometric methods, respectively. The amount of ROS production was estimated using chemiluminescence and fluorescence methods. Cell viability and apoptosis were detected by Annexin-V/propidium iodide detection kit. Basal estrone and progesterone secretion by N-GCs was significantly higher than that of PCO-GCs. Vit.D significantly increased aromatase and 3β-hydroxysteroid dehydrogenase activity in N-GCs and PCO-GCs. Basal expression and activity of GPx, in PCO-GCs were significantly lower than those of N-GCs. Treatment with vit.D significantly increased genes expression and enzyme activities in both groups. Basal ROS in PCO-GCs was markedly greater than that of N-GCs, which was attenuated by vit.D treatment. Cell apoptosis was directly correlated with ROS levels. We conclude that vit.D improved N-GCs and PCO-GCs functions through affecting steroidogenesis and enzymatic antioxidant defense. Under vit.D treatment, PCO-GCs could act more similar to N-GCs.

Masjedi F ，Keshtgar S ，Zal F ，Talaei-Khozani T ，Sameti S ，Fallahi S ，Kazeroni M ... -  《-》

Vitamin D3 regulates steroidogenesis in granulosa cells through AMP-activated protein kinase (AMPK) activation in a mouse model of polycystic ovary syndrome.

Bakhshalizadeh S ，Amidi F ，Shirazi R ，Shabani Nashtaei M ... -  《-》

Vitamin D receptor expression and potential role of vitamin D on cell proliferation and steroidogenesis in goat ovarian granulosa cells.

This study aimed to investigate the expression of the vitamin D receptor (VDR) in goat follicles and to determine the effects of Vit D3 supplementation on goat granulosa cells (GCs) function linked to follicular development. The results demonstrated that VDR was prominently localized in GCs, with expression increasing with follicle diameter. Addition of Vit D3 (1α,25-(OH)2VD3; 10 nM) to GCs caused an increase in VDR and in steroidogenic acute regulator (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA expression. Additionally, Vit D3 increased the cyclic adenosine monophosphate (cAMP), estradiol (E2), and progesterone (P4) levels, while it decreased anti-müllerian hormone receptor (AMHR) and follicle-stimulating hormone receptor (FSHR) mRNA expression (P < 0.05). Addition of FSH remarkably increased E2, P4, and cAMP levels (P < 0.05), and Vit D3 further enhanced the E2 and cAMP levels in the presence of FSH (P < 0.05). Vit D3 significantly induced the mRNA expression of CDK4 and CyclinD1, and downregulated P21 gene expression (P < 0.05). In addition, Vit D3 significantly decreased reactive oxygen species (ROS) production and increased the mRNA and protein expression of superoxide dismutase 2 (SOD2) and catalase (CAT) (P < 0.05). In conclusion, VDR is expressed in GCs of the goat ovaries and Vit D3 might play an important role in GCs proliferation by regulating cellular oxidative stress and cell cycle-related genes. Meanwhile, Vit D3 enhances the E2 and P4 output of GCs by regulating the expression of 3β-HSD and StAR and the level of cAMP, which regulate steroidogenesis, supporting a potential role for Vit D3 in follicular development.

Yao X ，Zhang G ，Guo Y ，Ei-Samahy M ，Wang S ，Wan Y ，Han L ，Liu Z ，Wang F ，Zhang Y ... -  《-》

Modulation of steroidogenesis by vitamin D3 in granulosa cells of the mouse model of polycystic ovarian syndrome.

Bakhshalizadeh S ，Amidi F ，Alleyassin A ，Soleimani M ，Shirazi R ，Shabani Nashtaei M ... -  《-》

Immunohistochemical study of steroidogenesis and cell proliferation in polycystic ovarian syndrome.

Takayama K ，Fukaya T ，Sasano H ，Funayama Y ，Suzuki T ，Takaya R ，Wada Y ，Yajima A ... -  《HUMAN REPRODUCTION》