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F. Schirra, T. Suzuki, D.P. Dickinson, D.J. Townsend, I.K. Gipson, D.A. Sullivan; Identification of Steroidogenic Enzyme mRNAs in Human Ocular Surface Tissues and Cells . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1025.
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Purpose: Sex steroids exert a significant impact on the health and well-being of the ocular surface. These hormones influence multiple aspects of the lacrimal and meibomian glands, conjunctiva and cornea, and have been linked to the development of many ocular surface pathologies. We hypothesize that these hormone actions, as in other tissues, occur predominantly after the local formation of androgens and estrogens from adrenal precursors. To begin to test this hypothesis, we examined whether human ocular surface tissues and cells contain the enzyme mRNAs necessary for the intracrine synthesis and metabolism of sex steroids. Methods: Total mRNA was isolated from human lacrimal and meibomian glands, immortalized corneal epithelial cells (gift from Santen Pharmaceutical, Japan) and transformed conjunctival epithelial cells. Samples were reverse transcribed to cDNA and analyzed for the presence of enzyme mRNAs by real-time PCR. Positive and negative controls included human placental cDNA and the absence of template, respectively. Results: Our findings demonstrated that human lacrimal and meibomian glands, and corneal and conjunctival epithelial cells, contain all of the following steroidogenic and metabolic enzyme mRNAs: steroid sulfatase (transforms the adrenal precursor dehydroepiandrosterone [DHEA]-sulfate into DHEA), 3ß-hydroxysteroid dehydrogenase (HSD) type 1 (converts DHEA into androstenedione [Δ4] or 5-androstene-3ß,17ß-diol [5-diol]),17ß-HSD types 1 and 3 (regulate the interconversion of DHEA and 5-diol, Δ4 and testosterone [T], estrone [E1] and estradiol ), aromatase (transforms Δ4 and T into E1 and E2) and glucuronosyltransferase (converts sex steroids into inactive glucuronidated metabolites). In contrast, only lacrimal and meibomian tissues contained detectable mRNA for sulfotransferase (converts sex steroids into sulfated metabolites). Conclusions: If the corresponding mRNAs are translated, our results indicate that human ocular surface tissues contain the enzymatic machinery necessary for the intracrine synthesis and metabolism of sex steroids. (Supported by research grants from NIH [EY05612], Allergan and the German Research Society DFG [Schi 562/1-1 & 1-2])
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