Ontogeny of glucocorticoid receptor and 11 beta-hydroxysteroid dehydrogenase type-1 gene expression identifies potential critical periods of glucocorticoid susceptibility during development

H J L Speirs, J R Seckl, R W Brown

Research output: Contribution to journalArticlepeer-review

Abstract

Glucocorticoids play important roles in organ development and 'fetal programming'. Fetal exposure to excess glucocorticoids reduces birth weight and causes later hypertension. To investigate these processes further we have determined the detailed ontogeny in the mouse of the glucocorticoid receptor (GR) and 11p-hydroxysteroid dehydrogenase type-1 (11beta-HSD1), which amplifies glucocorticoid levels locally; the ontogeny was determined using in situ hybridisation from embryonic day 9.5 (E9.5, term=E19) until after birth.

At E9.5 fetal GR mRNA levels are very low, except in fetal placenta. GR gene expression rises during gestation with striking tissue-specific differences in timing and extent. Before E13-5, an increase is clear in gastrointestinal (GI) and upper respiratory tracts, discrete central nervous system (CNS) regions, precartilage and especially in the liver (E10.5-E12). Later, further increases occur in lung, GI and upper respiratory tracts, muscle, pituitary and thymus. In a few tissues such increases are temporary, e.g. ureteric ducts (E13.5-E16.5) and pancreas (E14.5-E16.5, expression later filling sharply).

Fetal 11beta-HSD1 mRNA expression is first clearly observed at E14-5-E15, initially in the fetal placenta then in the umbilical cord. Later, 11betaHSD 1. expression is seen as follows: (i) from E15 in lung and liver, rising strongly; (ii) thymus, from E15 (lower level); (iii) at low levels in a few brain regions, including the hippocamptus (E16.5+); and (iv) in muscle group fascial planes and tendon insertions.

This is the first detailed study of the ontogeny of these two genes and, in combination with previous work on the ontogeny of 11 beta-HSD2 and the minineralocorticoid receptor, suggests potential critical periods of glucocorticoid sensitivity during development for several organ systems.

Original languageEnglish
Pages (from-to)105-116
Number of pages12
JournalJournal of Endocrinology
Volume181
Issue number1
Publication statusPublished - Apr 2004

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