title: Importance of ALDH1A enzymes in determining human testicular retinoic acid concentrations.
abstract: Retinoic acid (RA), the active metabolite of vitamin A, is required for spermatogenesis and many other biological processes. RA formation requires irreversible oxidation of retinal to RA by aldehyde dehydrogenase enzymes of the 1A family (ALDH1A). While ALDH1A1, ALDH1A2, and ALDH1A3 all form RA, the expression pattern and relative contribution of these enzymes to RA formation in the testis is unknown. In this study, novel methods to measure ALDH1A protein levels and intrinsic RA formation were used to accurately predict RA formation velocities in individual human testis samples and an association between RA formation and intratesticular RA concentrations was observed. The distinct localization of ALDH1A in the testis suggests a specific role for each enzyme in controlling RA formation. ALDH1A1 was found in Sertoli cells, while only ALDH1A2 was found in spermatogonia, spermatids, and spermatocytes. In the absence of cellular retinol binding protein (CRBP)1, ALDH1A1 was predicted to be the main contributor to intratesticular RA formation, but when CRBP1 was present, ALDH1A2 was predicted to be equally important in RA formation as ALDH1A1. This study provides a comprehensive novel methodology to evaluate RA homeostasis in human tissues and provides insight to how the individual ALDH1A enzymes mediate RA concentrations in specific cell types.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, School of Medicine, University of Washington, Seattle, WA 98195.
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Arnold
authors.affiliation: School of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman, WA 99164.
authors.forename: Travis
authors.initials: T
authors.lastname: Kent
authors.affiliation: School of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman, WA 99164.
authors.forename: Cathryn A
authors.initials: CA
authors.lastname: Hogarth
authors.affiliation: Center for Reproductive Medicine and Andrology, Munster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schlatt
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, School of Medicine, University of Washington, Seattle, WA 98195.
authors.forename: Bhagwat
authors.initials: B
authors.lastname: Prasad
authors.affiliation: Departments of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA 98195.
authors.forename: Michael
authors.initials: M
authors.lastname: Haenisch
authors.affiliation: Urology, School of Medicine, University of Washington, Seattle, WA 98195.
authors.forename: Thomas
authors.initials: T
authors.lastname: Walsh
authors.affiliation: Urology, School of Medicine, University of Washington, Seattle, WA 98195.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Muller
authors.affiliation: School of Molecular Biosciences and the Center for Reproductive Biology, Washington State University, Pullman, WA 99164.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Griswold
authors.affiliation: Medicine, School of Medicine, University of Washington, Seattle, WA 98195.
authors.forename: John K
authors.initials: JK
authors.lastname: Amory
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, School of Medicine, University of Washington, Seattle, WA 98195.
authors.forename: Nina
authors.initials: N
authors.lastname: Isoherranen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism; D002853:Chromatography, Liquid; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D013737:Testis / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism
chemical_list: D014212:Tretinoin; D000445:Aldehyde Oxidoreductases; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; C545372:ALDH1A2 protein, human; D050697:Retinal Dehydrogenase; C018699:aldehyde dehydrogenase (NAD(P)+)
keywords: aldehyde dehydrogenase 1A; mass spectrometry; testes