Antiandrogen Treatment Ameliorates Reproductive and Metabolic Phenotypes in the Letrozole-Induced Mouse Model of PCOS

Endocrinology
Genevieve E RyanPamela L Mellon

Abstract

Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by hyperandrogenism, anovulation, and polycystic ovaries. Although its etiology is unknown, excess androgens are thought to be a critical factor driving the pathology of PCOS. We previously demonstrated that continuous exposure to the aromatase inhibitor letrozole (LET) in mice produces many hallmarks of PCOS, including elevated testosterone (T) and luteinizing hormone, anovulation, and obesity. In the current study, we sought to determine whether androgen receptor (AR) actions are responsible for any of the phenotypes observed in LET mice. C57BL/6 female mice were subcutaneously implanted with LET or placebo control and subsequently treated with the nonsteroidal AR antagonist flutamide or vehicle control. Flutamide treatment in LET females reversed elevated T levels and restored ovarian expression of Cyp17a1 (critical for androgen synthesis) to normal levels. Pituitary expression of Lhb was decreased in LET females that received flutamide treatment, with no changes in expression of Fshb or Gnrhr. Flutamide treatment also restored estrous cycling and reduced the number of ovarian cyst-like follicles in LET females. Fu...Continue Reading

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Citations

Apr 21, 2020·Endocrine Reviews·Elisabet Stener-VictorinDavid H Abbott
May 3, 2018·Endocrinology·Teresa K Woodruff
Aug 31, 2019·Medical Sciences : Open Access Journal·Valentina Rodriguez Paris, Michael J Bertoldo
Jan 4, 2021·Molecular and Cellular Endocrinology·Larissa Rugila S StopaCristiane Mota Leite
Mar 20, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Si-Wei ZhangLing Wang
Mar 26, 2021·Human Reproduction Update·Sebastião Freitas de MedeirosRobert John Norman
Jul 22, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Emmi RotgersHumphrey Hung-Chang Yao
Dec 11, 2021·International Journal of Gynaecology and Obstetrics : the Official Organ of the International Federation of Gynaecology and Obstetrics·Maryam AsgharniaAhmad Hosseini

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