A pilot study evaluating dosing tolerability of 17α-estradiol in male common marmosets (Callithrix jacchus).

Autor: Sathiaseelan R; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Chapman S212, Oklahoma City, OK, 73104, USA., Isola JVV; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Chapman S212, Oklahoma City, OK, 73104, USA., Santín-Márquez R; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Chapman S212, Oklahoma City, OK, 73104, USA., Adekunbi D; Barshop Institute for Longevity & Aging Studies, University of Texas Health San Antonio, San Antonio, TX, USA., Fornalik M; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Chapman S212, Oklahoma City, OK, 73104, USA., Salmon AB; Barshop Institute for Longevity & Aging Studies, University of Texas Health San Antonio, San Antonio, TX, USA.; Department of Molecular Medicine, University of Texas Health San Antonio, San Antonio, TX, USA.; South Texas Veterans Affairs Medical Center, San Antonio, TX, USA., Stout MB; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Chapman S212, Oklahoma City, OK, 73104, USA. michael-stout@omrf.org.; Oklahoma City Veterans Affairs Medical Center, Oklahoma City, OK, USA. michael-stout@omrf.org.
Jazyk: angličtina
Zdroj: GeroScience [Geroscience] 2024 Aug 06. Date of Electronic Publication: 2024 Aug 06.
DOI: 10.1007/s11357-024-01311-z
Abstrakt: 17α-estradiol extends healthspan and lifespan in male mice without significant feminization or deleterious effects on reproductive function, making it a candidate for human translation. However, studies in animal models that more accurately replicate human physiology are necessary to establish 17α-estradiol dosing standards for clinical trials. This study evaluated the tolerability of 17α-estradiol treatment in the common marmoset over a short treatment duration. We found that male marmosets tolerated two dosing regimens (0.37-0.47 or 0.62-0.72 mg/kg/day) as evidenced by the absence of gastrointestinal distress, changes in vital signs, or overall health conditions. 17α-estradiol treatment mildly decreased body mass, adiposity, and glycosylated hemoglobin, although these changes were not statistically significant in most instances. However, neither dose of 17α-estradiol elicited feminization in our study, thereby suggesting that optimized dosing regimens may provide health benefits without feminization in primates. Additional studies are needed to determine if longer duration treatments would also be nonfeminizing and elicit significant health benefits, which would aid in developing dosing regimens targeting healthy aging in humans.
(© 2024. The Author(s), under exclusive licence to American Aging Association.)
Databáze: MEDLINE
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