PMID- 10224232
OWN - NLM
STAT- MEDLINE
DCOM- 19990525
LR  - 20190516
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 13
IP  - 8
DP  - 1999 May
TI  - Paracrine glucocorticoid activity produced by mouse thymic epithelial cells.
PG  - 893-901
AB  - Previous data have suggested that glucocorticoids (GCs) are involved in the 
      differentiation of thymocytes into mature T cells. In this report we demonstrate 
      that the mouse thymic epithelial cells (TEC) express the cytochrome P450 
      hydroxylases Cyp11A1, Cyp21, and Cyp11B1. These enzymes, in combination with 
      3beta-hydroxysteroid dehydrogenase (3betaHSD), convert cholesterol into 
      corticosterone, the major GC in rodents. In addition, when TEC were cocultured 
      with 'reporter cells' containing the glucocorticoid receptor (GR) and a 
      GR-dependent reporter gene, a specific induction of reporter gene activity was 
      observed. Induction of reporter gene activity was blocked when the TEC and 
      reporter cells were incubated in the presence of the Cyp11B1 inhibitor metyrapone 
      or the 3betaHSD inhibitor trilostane, as well as by the GR antagonist RU486. 
      Coculturing of TEC with thymocytes induced apoptosis in the latter, which was 
      partially blocked by the enzyme inhibitors and RU486. We conclude that TEC 
      secrete a GC hormone activity and suggest a paracrine role for this in thymocyte 
      development.
FAU - Pazirandeh, A
AU  - Pazirandeh A
AD  - Department of Medical Nutrition, Karolinska Institutet, Huddinge University 
      Hospital, Novum F-60, SE-141 86 Huddinge, Sweden.
FAU - Xue, Y
AU  - Xue Y
FAU - Rafter, I
AU  - Rafter I
FAU - Sjovall, J
AU  - Sjovall J
FAU - Jondal, M
AU  - Jondal M
FAU - Okret, S
AU  - Okret S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (DNA Primers)
RN  - 0 (Glucocorticoids)
RN  - 0 (Receptors, Glucocorticoid)
RN  - EC 1.1.- (3-Hydroxysteroid Dehydrogenases)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 1.14.14.16 (Steroid 21-Hydroxylase)
RN  - EC 1.14.15.4 (Steroid 11-beta-Hydroxylase)
RN  - EC 1.14.15.6 (Cholesterol Side-Chain Cleavage Enzyme)
SB  - IM
MH  - 3-Hydroxysteroid Dehydrogenases/metabolism
MH  - Animals
MH  - Apoptosis
MH  - Base Sequence
MH  - COS Cells
MH  - Cell Differentiation
MH  - Cholesterol Side-Chain Cleavage Enzyme/genetics/metabolism
MH  - Coculture Techniques
MH  - DNA Primers/genetics
MH  - Epithelial Cells/cytology/metabolism
MH  - Gene Expression
MH  - Genes, Reporter
MH  - Glucocorticoids/*biosynthesis
MH  - Luciferases/genetics
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Paracrine Communication/*physiology
MH  - Receptors, Glucocorticoid/metabolism
MH  - Steroid 11-beta-Hydroxylase/genetics/metabolism
MH  - Steroid 21-Hydroxylase/genetics/metabolism
MH  - Thymus Gland/cytology/*metabolism
EDAT- 1999/05/04 00:00
MHDA- 1999/05/04 00:01
CRDT- 1999/05/04 00:00
PHST- 1999/05/04 00:00 [pubmed]
PHST- 1999/05/04 00:01 [medline]
PHST- 1999/05/04 00:00 [entrez]
AID - 10.1096/fasebj.13.8.893 [doi]
PST - ppublish
SO  - FASEB J. 1999 May;13(8):893-901. doi: 10.1096/fasebj.13.8.893.