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Updated: Apr 18, 2026

Evaluation of Hepatic Glucose Production in a Polycystic Ovary Syndrome Mouse Model
Published on: March 5, 2022
Functional genomics of PCOS: from GWAS to molecular mechanisms
Jan M McAllister1, Richard S Legro2, Bhavi P Modi3
1Department of Pathology, Penn State Hershey College of Medicine, Hershey, PA, USA; Department of Obstetrics and Gynecology, Penn State Hershey College of Medicine, Hershey, PA, USA.
Abstract:
Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterized by increased ovarian androgen biosynthesis, anovulation, and infertility. PCOS has a strong heritable component based on familial clustering and twin studies. Genome-wide association studies (GWAS) identified several PCOS candidate loci including LHCGR, FSHR, ZNF217, YAP1, INSR, RAB5B, and C9orf3. We review the functional roles of strong PCOS candidate loci focusing on FSHR, LHCGR, INSR, and DENND1A. We propose that these candidates comprise a hierarchical signaling network by which DENND1A, LHCGR, INSR, RAB5B, adapter proteins, and associated downstream signaling cascades converge to regulate theca cell androgen biosynthesis. Future elucidation of the functional gene networks predicted by the PCOS GWAS will result in new diagnostic and therapeutic approaches for women with PCOS.
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