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Tissue-Specific Messenger Ribonucleic Acid Expression of 11ß-Hydroxysteroid Dehydrogenase Types 1 and 2 and the Glucocorticoid Receptor within Rat Placenta Suggests Exquisite Local Control of Glucocorticoid Action¹

Department of Medicine (B.J.W., R.B., R.W.B., J.R.S.), The University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU Scotland, United Kingdom; and Department of Anatomy and Human Biology (B.J.W.), The University of Western Australia, Nedlands, Perth, Western Australia 6907, Australia

Address all correspondence and requests for reprints to: Dr. Brendan J. Waddell, Department of Anatomy and Human Biology, The University of Western Australia, Nedlands, Perth, Western Australia 6907, Australia. E-mail: bwaddell{at}anhb.uwa.edu.au

Placental 11ß-hydroxysteroid dehydrogenase (11ß-HSD) regulates transplacental passage of maternal glucocorticoids to the fetus and is thus a key determinant of fetal glucocorticoid levels. It has also been proposed that placental 11ß-HSD expression may influence local glucocorticoid actions by regulating access of corticosterone to the glucocorticoid receptor (GR) or mineralocorticoid receptor (MR). Therefore, the present study used a rat model to assess whether the GR or MR are coexpressed with the two forms of 11ß-HSD (types 1 and 2) in the placental labyrinth zone, the major site of maternal-fetal transfer, and in the basal zone, the primary site of placental hormone synthesis. In situ hybridization analysis was used to assess messenger RNA (mRNA) expression for the GR, MR, 11ß-HSD-1, and 11ß-HSD-2 in the two placental zones on days 16, 19 and 22 of pregnancy (term = day 23). Whereas expression of the GR appeared relatively unchanged in both zones at these three stages of pregnancy, that of 11ß-HSD-1 clearly increased in the labyrinth zone but fell in basal zone, whereas the opposite pattern of expression was observed for 11ß-HSD-2. MR expression was not detected at any stage. The pattern of placental 11ß-HSD-2 mRNA expression over days 16, 19, and 22 of pregnancy was paralleled by changes in 11ß-HSD-2-specific bioactivity, but despite clear expression of 11ß-HSD-1 mRNA, no bioactivity attributable to this enzyme was measurable in either placental zone. To assess the role of fetal adrenal maturation on these changes in 11ß-HSD, two experimental models, maternal adrenalectomy and fetectomy, were employed. Maternal adrenalectomy on day 13 advanced maturation of the fetal adrenal cortex but had no effect on 11ß-HSD-2 bioactivity in either of the placental zones at day 19. Placental 11ß-HSD-2 bioactivity on day 22 was also unaffected by fetectomy 3 or 6 days earlier. In conclusion, the consistent expression of the GR in the two placental zones late in pregnancy suggests that concomitant and marked changes in 11ß-HSD-1 and 11ß-HSD-2 expression could have a major influence on glucocorticoid action in the placenta at this time. Moreover, the changes in 11ß-HSD expression appear to be unrelated to development of the fetal adrenal cortex and are likely to reduce the placental glucocorticoid barrier near the end of pregnancy.

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