title: Differential Effects of Hormones on Cellular Metabolism in Keratoconus In Vitro.
abstract: Keratoconus (KC) is a corneal thinning disease with an onset commonly immediately post-puberty and stabilization by 40 to 50 years of age. The role of hormones in regulating corneal tissue structure in homeostatic and pathological conditions is unknown. Our group recently linked altered hormone levels to KC. Our current study sought to investigate and delineate the effects of exogenous hormones, such as androgen, luteotropin, and estrogen, on corneal stroma bioenergetics. We utilized our established 3D in vitro model to characterize the effects of DHEA, prolactin, 17β-estradiol on insulin-growth factor-1 and -2 (IGF-1, -2) signaling and metabolic function in primary corneal fibroblasts from healthy controls (HCFs) and KC patients (HKCs). Our data showed that exogenous DHEA significantly downregulated IGF-1 and its receptor in both HCFs and HKCs with HKCs showing consistently lower basal pentose phosphate flux. Prolactin caused no significant change in IGF-1 levels and an increase in IGF-2 in HKCs correlating with an increase in ATP and NADH levels. 17β-estradiol led to a significant upregulation in pentose phosphate flux and glycolytic intermediates in HCFs. Our results identified hormone-specific responses regulated in HKCs compared to HCFs revealing a novel role for hormones on bioenergetics in KC.
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
authors.forename: Tina B
authors.initials: TB
authors.lastname: McKay
authors.affiliation: Department of Ophthalmology, Aarhus University Hospital, Aarhus C DK-800, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Hjortdal
authors.affiliation: Department of Ophthalmology, Aarhus University Hospital, Aarhus C DK-800, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Sejersen
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.|Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Karamichos
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D007640:Keratoconus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D011388:Prolactin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D006728:Hormones; C583557:IGF1 protein, human; C035170:IGF2 protein, human; D003687:Dehydroepiandrosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011388:Prolactin