Expression of molecular equivalent of hypothalamic-pituitary-adrenal axis in adult retinal pigment epithelium.
We have investigated expression of molecular elements of the hypothalamic-pituitary-adrenal (HPA) axis in the human retinal pigment epithelium (RPE) cells. The presence of corticotropin-releasing factor (CRF); urocortins I, II and III; CRF receptor type 1 (CRFR1); POMC and prohormone convertases 1 and 2 (PC1 and PC2) mRNAs were shown by RT-PCR; the protein products were detected by ELISA, western blot or immunocytochemical methods in an ARPE-19 cell line derived from an adult human donor. CRFR2 was below the level of detectability. The CRFR1 was functional as evidenced by CRF stimulation of cAMP and inositol triphosphate production as well as by ligand induction of transcriptional activity of inducible cis-elements cAMP responsive element (CRE), activator protein 1 responsive element (AP-1) and POMC promoter) in ARPE-19 using luciferase reporter assay. Immunoreactivities representative of CRF, pre-urocortin, CRFR1 receptor and ACTH were also detected in mouse retina by in situ immunocytochemistry. Finally, using RT-PCR, we detected expression of genes encoding four key enzymes participating in steroids synthesis (CYP11A1, CYP11B1, CYP17 and CYP21A2) and showed transformation of progesterone into cortisol-immunoreactivity in cultured ARPE-19 cells. Therefore, we suggest that ocular tissue expresses CRF-driven signalling system that follows organisational structure of the HPA axis.
Zmijewski
Michal A
MA
Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, 930 Madison Avenue, RM525, Memphis, Tennessee 38163, USA.
Sharma
Rajesh K
RK
Slominski
Andrzej T
AT
D000305:Adrenal Cortex Hormones / Q000032:analysis* / Q000235:genetics; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D000818:Animals; D002460:Cell Line; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000032:analysis / Q000235:genetics / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015870:Gene Expression; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D007028:Hypothalamic Hormones / Q000032:analysis* / Q000235:genetics; D007150:Immunohistochemistry; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D051379:Mice; D010857:Pigment Epithelium of Eye / Q000737:chemistry / Q000378:metabolism*; D010907:Pituitary Hormones / Q000032:analysis* / Q000235:genetics; D011333:Pro-Opiomelanocortin / Q000032:analysis / Q000235:genetics; D011374:Progesterone / Q000378:metabolism; D045664:Proprotein Convertase 1 / Q000235:genetics; D045706:Proprotein Convertase 2 / Q000235:genetics; D018019:Receptors, Corticotropin-Releasing Hormone / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D054832:Urocortins; D000099052:CRF Receptor, Type 1
D000305:Adrenal Cortex Hormones; D017931:DNA Primers; D007028:Hypothalamic Hormones; D010907:Pituitary Hormones; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D011374:Progesterone; D000099052:CRF Receptor, Type 1; D011333:Pro-Opiomelanocortin; D015544:Inositol 1,4,5-Trisphosphate; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D013254:Steroid 17-alpha-Hydroxylase; D013252:Steroid 11-beta-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D045664:Proprotein Convertase 1; D045706:Proprotein Convertase 2; D006854:Hydrocortisone