Endogenous Androgen Deficiency Enhances Diet-Induced Hypercholesterolemia and Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice

Nicholas W. Hatch, Sarah J. Srodulski, Huei Wei Chan, Xuan Zhang, Lisa R. Tannock, Victoria L. King

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Background: Despite numerous clinical and animal studies, the role of sex steroid hormones on lipoprotein metabolism and atherosclerosis remain controversial. Objective: We sought to determine the effects of endogenous estrogen and testosterone on lipoprotein levels and atherosclerosis using mice fed a low-fat diet with no added cholesterol. Methods: Male and female low-density lipoprotein receptor-deficient mice were fed an open stock low-fat diet (10% of kcals from fat) for 2, 4, or 17 weeks. Ovariectomy, orchidectomy, or sham surgeries were performed to evaluate the effects of the presence or absence of endogenous hormones on lipid levels, lipoprotein distribution, and atherosclerosis development. Results: Female mice fed the study diet for 17 weeks had a marked increase in levels of total cholesterol, triglycerides, apolipoprotein-B containing lipoproteins, and atherosclerosis compared with male mice. Surprisingly, ovariectomy in female mice had no effect on any of these parameters. In contrast, castration of male mice markedly increased total cholesterol concentrations, triglycerides, apolipoprotein B-containing lipoproteins, and atherosclerotic lesion formation compared with male and female mice. Conclusions: These data suggest that endogenous androgens protect against diet-induced increases in cholesterol concentrations, formation of proatherogenic lipoproteins, and atherosclerotic lesions formation. Conversely orchidectomy, which decreases androgen concentrations, promotes increases in cholesterol concentrations, proatherogenic lipoprotein formation, and atherosclerotic lesion formation in low-density lipoprotein receptor-deficient mice in response to a low-fat diet.

Original languageEnglish
Pages (from-to)319-328
Number of pages10
JournalGender Medicine
Issue number5
StatePublished - Oct 2012

Bibliographical note

Funding Information:
The authors thank Eboni Lewis and Deborah Howatt for sharing their technical expertise. This work was funded by grants from the National Institutes of Health ( P20RR021954 and HL082835 to Dr. King and HL82772 to Dr. Tannock). Drs. King and Tannock designed experiments, interpreted data, and wrote the manuscript. Dr. Zhang performed ovariectomies and orchidectomies. Dr. Hatch and Ms. Srodulski performed experiments and interpreted data. Drs. Chan and Zhang performed biological assays. Drs. Hatch, Chan, Zhang, and Ms. Srodulski all commented on the manuscript. Dr. Hatch and Ms. Srodulski contributed equally to this work.


  • androgen
  • atherosclerosis
  • cholesterol
  • estrogen

ASJC Scopus subject areas

  • Gender Studies


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