Abstract
BackgroundPolycystic ovary syndrome (PCOS) is a complex genetic disease with multifarious phenotypes. Many researches use dehydroepiandrosterone (DHEA) to induce PCOS in pubertal mouse models. The aim of this study was to investigate the role of GPR1 in dehydroepiandrosterone (DHEA)-induced hyperandrogenized mice.MethodsPrepubertal C57BL/6 mice (25 days of age) and Gpr1-deficient mice were each divided into two groups and injected daily with sesame oil with or without DHEA (6 mg/100 g) for 21 consecutive days. Hematoxylin and eosin (H&E) staining was performed to determine the characteristics of the DHEA-treated ovaries. Real-time PCR was used to examine steroid synthesis enzymes gene expression. Granulosa cell was cultured to explore the mechanism of DHEA-induced, GPR1–mediated estradiol secretion.ResultsDHEA treatment induced some aspects of PCOS in wild-type mice, such as increased body weight, elevated serum testosterone, increased number of small, cystic, atretic follicles, and absence of corpus luteum in ovaries. However, Gpr1 deficiency significantly attenuated the DHEA-induced weight gain and ovarian phenotype, improving steroidogenesis in ovaries and estradiol synthesis in cultured granulosa cells, partially through mTOR signaling.ConclusionsIn conclusion, Gpr1 deficiency leads to the improvement of steroid synthesis in mice hyperandrogenized with DHEA, indicating that GPR1 may be a therapeutic target for DHEA-induced hyperandrogenism.
Highlights
Polycystic ovary syndrome (PCOS) is a complex genetic disease with multifarious phenotypes
The serum lipid levels of wild type mice were not affected by DHEA, while in Gpr1-deficient mice, LDL levels were significantly elevated after DHEA treatment
Testosterone levels were significantly greater in both wild type and Gpr1 knockout mice after DHEA treatment than they were in the control mice, confirming proper establishment of the in vivo hyperandrogenism model
Summary
Polycystic ovary syndrome (PCOS) is a complex genetic disease with multifarious phenotypes. Many researches use dehydroepiandrosterone (DHEA) to induce PCOS in pubertal mouse models. Synthesized mainly in the adrenal zona reticularis [1], it is an important precursor in follicular steroidogenesis and plays roles in protecting the central nervous system, preventing neurodegenerative diseases [2], improving depression [3], regulating and stabilizing inflammation and cellular immune functions [4], improving blood lipid metabolism [5], preventing osteoporosis [6], and protecting the cardiovascular system [7]. DHEA is generally increased in women with polycystic ovary syndrome (PCOS) [10]. Women with PCOS are at high risk of developing diabetes, insulin resistance, metabolic dysfunction, glucose intolerance, and cardiovascular disease [12]
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