{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T17:56:42Z","timestamp":1788631002545,"version":"build-2803163510"},"reference-count":88,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T00:00:00Z","timestamp":1619308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM121334"],"award-info":[{"award-number":["P20GM121334"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM104357"],"award-info":[{"award-number":["P20GM104357"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R21DK113500"],"award-info":[{"award-number":["R21DK113500"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["P01HL51971"],"award-info":[{"award-number":["P01HL51971"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>SARS-CoV-2, the causative agent of COVID-19, infects host cells using the angiotensin I converting enzyme 2 (ACE2) as its receptor after priming by host proteases, including TMPRSS2. COVID-19 affects multiple organ systems, and male patients suffer increased severity and mortality. Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in reproductive-age women and is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. PCOS is associated with obesity and cardiometabolic comorbidities, both being risk factors associated with severe COVID-19 pathology. We hypothesize that elevated androgens in PCOS regulate SARS-CoV-2 entry proteins in multiple tissues increasing the risk for this population. Female mice were treated with dihydrotestosterone (DHT) for 90 days. Body composition was measured by EchoMRI. Fasting glucose was determined by an enzymatic method. mRNA and protein levels of ACE2, Tmprss2, Cathepsin L, Furin, Tmprss4, and Adam17 were quantified by RT-qPCR, Western-blot, or ELISA in tissues, serum, and urine. DHT treatment increased body weight, fat and lean mass, and fasting glucose. Ace2 mRNA was upregulated in the lung, cecum, heart, and kidney, while downregulated in the brain by DHT. ACE2 protein was upregulated by DHT in the small intestine, heart, and kidney. The SARS-CoV-2 priming proteases Tmprss2, Cathepsin L, and Furin mRNA were upregulated by DHT in the kidney. ACE2 sheddase Adam17 mRNA was upregulated by DHT in the kidney, which corresponded with increased urinary ACE2 in DHT treated mice. Our results highlight the potential for increased cardiac, renal, and gastrointestinal dysfunction in PCOS women with COVID-19.<\/jats:p>","DOI":"10.3390\/ijms22094472","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T22:31:39Z","timestamp":1619389899000},"page":"4472","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["SARS-CoV-2 Viral Entry Proteins in Hyperandrogenemic Female Mice: Implications for Women with PCOS and COVID-19"],"prefix":"10.3390","volume":"22","author":[{"given":"Alexandra M.","family":"Huffman","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Women\u2019s Health Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Cardio Renal Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4421-0686","authenticated-orcid":false,"given":"Samar","family":"Rezq","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Women\u2019s Health Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Cardio Renal Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelina","family":"Basnet","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Women\u2019s Health Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Cardio Renal Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7295-1871","authenticated-orcid":false,"given":"Licy L.","family":"Yanes Cardozo","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Women\u2019s Health Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Cardio Renal Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7268-9690","authenticated-orcid":false,"given":"Damian G.","family":"Romero","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Women\u2019s Health Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Cardio Renal Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hoffmann, M., Hofmann-Winkler, H., and P\u00f6hlmann, S. 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