Abstract
Background
Under stress conditions, luteinizing hormone (LH)-mediated ovulation is inhibited, resulting in insufficient oocyte production and excretion during follicular development. When the body is stressed, a large amount of corticosterone (CORT) is generated, which will lead to disorder of the body's endocrine system and damage to the body. Our previous work showed that corticosterone can block follicular development in mice. Since LH acts through binding with the LH receptor (LHR), the present study aimed to investigate whether and how CORT influence luteinizing hormone receptor expression in mouse ovarian granulosa cells (GCs).
Methods
For this purpose, 3-week-old ICR female mice were injected intraperitoneally with pregnant horse serum gonadotropin (PMSG). Meanwhile, the treatment group were injected with corticosterone corticosterone (1 mg/mouse) at intervals of 8 h; while the control group was injected with same volume of methyl sulfoxide (DMSO). Granulosa cells were collected at 24 h, 48 h, and 55 h after PMSG injection. For in vitro experiments, mice granulosa cells obtained from healthy follicles were treated with corticosterone alone, or together with inhibitors against glucocorticoid receptor (GR).
Results
The results showed that corticosterone caused down-regulation of luteinizing hormone receptor expression in granulosa cells, which was accompanied by impaired cell viability. Moreover, the effects of corticosterone was mediated by binding to its receptor in granulosa cells. Further investigations revealed that glucocorticoid receptor might regulated the transcription of luteinizing hormone receptor through inhibiting the expression of luteinizing hormone receptor transcription factors, including AP1 and CREB.
Conclusions
Our findings suggested a possible mechanism of corticosterone-induced anovulation involving the inhibition of luteinizing hormone receptor expression in granulosa cells by corticosterone-glucocorticoid receptor-AP1 / CREB axis.
Melatonin Does Not Affect Progesterone Basal Secretion but Suppresses the Luteinizing Hormone Receptor Expression in Granulosa Cells of the Japanese Quail
