Laboratorio de Biología Celular y Molecular Aplicada, Facultad de Ciencias Veterinarias, Universidad Nacional del Litoral, Argentina; Instituto de Ciencias Veterinarias del Litoral (ICiVet-Litoral), Consejo Nacional de Investigaciones Científicas y Tecnológicas, (CONICET), Argentina.
Domest Anim Endocrinol. 2013 Oct;45(3):126-40. doi: 10.1016/j.domaniend.2013.07.001. Epub 2013 Aug 13.
Cystic ovarian disease (COD) is an important cause of infertility in cattle, and ACTH has been involved in regulatory mechanisms related to ovarian function associated with ovulation, steroidogenesis, and luteal function. Here, we examined the localization of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and 11βHSD2 proteins in the ovary of healthy cows and animals with spontaneous and ACTH-induced COD and the in vitro response of the follicular wall exposed to ACTH. After stimulation by ACTH, we documented changes in 11βHSD expression and cortisol secretion by the follicular wall of large antral and follicular cysts. Follicular cysts showed a higher constitutive expression of both enzymes, whereas ACTH induced an increase in 11βHSD1 in tertiary follicles and follicular cysts and a decrease in 11βHSD2 in follicular cysts. Moderate expression of 11βHSD1 was observed by immunohistochemistry in granulosa of control animals, with an increase (P < 0.05) from primary to secondary, tertiary, and atretic follicles. The level of immunostaining in theca interna was lower than that in granulosa. The expression of 11βHSD2 was lower in the granulosa of primary follicles than in that of secondary, tertiary, and atretic follicles and was lower in the theca interna than in the granulosa. In ACTH-induced and spontaneously occurring follicular cysts, differences from controls were observed only in the expression of 11βHSD1 in the granulosa, being higher (P < 0.05) than in tertiary follicles. These findings indicate that follicular cysts may be exposed to high local concentrations of active glucocorticoids and indicate a local role for cortisol in COD pathogenesis and in regulatory mechanisms of ovarian function.
多囊卵巢疾病(COD)是奶牛不孕的重要原因,而 ACTH 参与了与排卵、类固醇生成和黄体功能相关的卵巢功能调节机制。在这里,我们研究了健康奶牛和患有自发性和 ACTH 诱导的 COD 的动物的卵巢中 11β-羟类固醇脱氢酶 1(11βHSD1)和 11βHSD2 蛋白的定位,以及暴露于 ACTH 的卵泡壁的体外反应。在 ACTH 刺激后,我们记录了大腔卵泡和卵泡囊肿的卵泡壁中 11βHSD 表达和皮质醇分泌的变化。卵泡囊肿表现出两种酶的更高组成型表达,而 ACTH 诱导三级卵泡和卵泡囊肿中的 11βHSD1 增加,而卵泡囊肿中的 11βHSD2 减少。在对照动物的颗粒细胞中,通过免疫组织化学观察到 11βHSD1 的中度表达,从初级到次级、三级和闭锁卵泡均有增加(P < 0.05)。颗粒细胞内的免疫染色水平低于颗粒细胞。初级卵泡的颗粒细胞中 11βHSD2 的表达低于次级、三级和闭锁卵泡,颗粒细胞中的表达低于膜细胞。在 ACTH 诱导和自发发生的卵泡囊肿中,与对照组相比,仅在颗粒细胞中观察到 11βHSD1 的表达存在差异,比三级卵泡更高(P < 0.05)。这些发现表明,卵泡囊肿可能暴露于高局部浓度的活性糖皮质激素,并表明皮质醇在 COD 发病机制和卵巢功能调节机制中具有局部作用。