The Vitamin D Analogs Doxercalciferol Induces Weight Loss and Improves Fertility in a Mouse Model of Polycystic Ovary Syndrome.

PURPOSE: Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-age women. Several published studies demonstrated the therapeutic potential of vitamin D on PCOS condition, but vitamin D supplementation leads to only modest improvements. Doxercalciferol (Dox) is a highly potent vitamin D receptor (VDR) agonist that binds to VDR with at least 150 times greater affinity than other vitamin D compounds. In this study, we hypothesized that the therapeutic potential of Dox may reverse PCOS-related phenotypes more efficiently. METHOD: We first analyzed the regulatory potential of Dox in fat metabolism by comparing adipocyte proliferation and differentiation in our in vitro model. We also injected Dox into our mouse model of PCOS to analyze the therapeutic effect of Dox treatment on various PCOS-related parameters and fertility. RESULT: Dox treatment inhibited the proliferation of both adipose lineage cells and androgen-producing H295R cells in a dose-dependent manner. PCOS-related outcomes such as body weight and fertility rate were significantly reversed in Dox-treated PCOS mice model. CONCLUSION: Our study revealed that vitamin D analogs are a promising family of compounds for reducing body weight and reversing infertility in an animal model of PCOS.