PMID- 10090587 OWN - NLM STAT- MEDLINE DCOM- 19990504 LR - 20190905 IS - 0721-832X (Print) IS - 0721-832X (Linking) VI - 237 IP - 3 DP - 1999 Mar TI - Human trabecular meshwork cells as a thyroid hormone target tissue: presence of functional thyroid hormone receptors. PG - 231-40 AB - PURPOSE: To determine whether human trabecular meshwork cells (HTM) are a potential target tissue for thyroid hormone (3,3',5-triiodothyronine, T3). METHODS: Cultured HTM were assayed for the presence of thyroid hormone receptors (TRs) and retinoid X receptors (RXRs) by reverse-transcriptase polymerase chain reaction (RT-PCR) to detected TR and RXR mRNA, and by immunohistochemistry to detect nuclear TR and RXR proteins. Functionality of the TR was determined by analysis of 125I-T3 binding affinity and capacity in HTM nuclear extracts. Effects of T3 on modulation of hyaluronic acid (HA) levels in HTM were measured as a function of dose and duration of T3 administration. RESULTS: Analysis of RT-PCR and immunohistochemistry demonstrated that cultured HTM expressed TRalpha1, TRalpha2, and TRbeta1 but not TRbeta2; and RXRalpha but not RXRbeta and RXRgamma isoforms. Saturation binding and analysis of 125I-T3 to HTM nuclear extracts revealed Kd of 57 pM. The number of T3 binding sites extrapolated from a Scatchard plot was 7.3 x 10(10)/microg of HTM nuclear protein extract. T3 supplementation reduced the concentration of HA in the cell medium by 32-43% compared to cells grown in the absence of T3. CONCLUSIONS: Cultured HTM express three TR isoforms and one RXR isoform, bind T3 with an affinity similar to that of TR in responsive cells, and modulate their HA production in response to T3. These findings indicate that the human trabecular meshwork tissue has the capacity to respond to thyroid hormones. FAU - Duncan, K G AU - Duncan KG AD - Department of Ophthalmology, University of California, San Francisco 94143, USA. FAU - Jumper, M D AU - Jumper MD FAU - Ribeiro, R C AU - Ribeiro RC FAU - Bailey, K R AU - Bailey KR FAU - Yen, P M AU - Yen PM FAU - Sugawara, A AU - Sugawara A FAU - Patel, A AU - Patel A FAU - Stern, R AU - Stern R FAU - Chin, W W AU - Chin WW FAU - Baxter, J D AU - Baxter JD FAU - Schwartz, D M AU - Schwartz DM LA - eng GR - EY02162/EY/NEI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - Germany TA - Graefes Arch Clin Exp Ophthalmol JT - Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie JID - 8205248 RN - 0 (DNA Primers) RN - 0 (Nuclear Proteins) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Retinoic Acid) RN - 0 (Receptors, Thyroid Hormone) RN - 0 (Retinoid X Receptors) RN - 0 (Transcription Factors) RN - 06LU7C9H1V (Triiodothyronine) SB - IM MH - Adult MH - Cell Count/drug effects MH - Cells, Cultured/drug effects MH - DNA Primers/chemistry MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Nuclear Proteins/drug effects/genetics/metabolism MH - RNA, Messenger/analysis MH - Receptors, Retinoic Acid/drug effects/genetics/metabolism MH - Receptors, Thyroid Hormone/drug effects/genetics/*metabolism MH - Retinoid X Receptors MH - Reverse Transcriptase Polymerase Chain Reaction MH - Trabecular Meshwork/cytology/drug effects/*metabolism MH - Transcription Factors/drug effects/genetics/metabolism MH - Triiodothyronine/pharmacology EDAT- 1999/03/25 00:00 MHDA- 1999/03/25 00:01 CRDT- 1999/03/25 00:00 PHST- 1999/03/25 00:00 [pubmed] PHST- 1999/03/25 00:01 [medline] PHST- 1999/03/25 00:00 [entrez] AID - 10.1007/s004170050224 [doi] PST - ppublish SO - Graefes Arch Clin Exp Ophthalmol. 1999 Mar;237(3):231-40. doi: 10.1007/s004170050224.