Regulation of 11 beta-hydroxysteroid dehydrogenase type 2 activity in ovine placenta by fetal cortisol

Abstract

The effect of fetal cortisol on the activity of the type 2 isoform of the enzyme, 11 -hydroxysteroid dehydrogenase (11 -HSD2), was examined in ovine placenta and fetal kidney by measuring tissue 11 -HSD2 activity during late gestation when endogenous fetal cortisol levels rise and after exogenous cortisol administration to immature fetuses before the prepartum cortisol surge. Placental 11 -HSD2 activity decreased between 128-132 days and term (]145 days of gestation) in association with the normal prepartum increase in fetal plasma cortisol. Raising fetal cortisol levels to prepartum values in the immature fetus at 128-132 days of gestation reduced placental 11 -HSD2 activity to term values. In contrast, 11 -HSD2 activity in the fetal renal cortex was unaffected by gestational age or cortisol infusion. When all the data were combined, there was an inverse correlation between the log fetal plasma cortisol level at delivery and placental 11 -HSD2 activity, expressed both on a weight-specific basis and per mg placental protein.Fetal cortisol therefore appears to be a physiological regulator of placental, but not renal, 11 -HSD2 activity in fetal sheep during late gestation. These findings have important implications, not only for glucocorticoid exposure in utero, but also for the local actions of cortisol within the placental tissues that are involved in initiating parturition in the sheep.

Mechanism of the delayed puberty onset in offspring of rats that consumed aqueous extract of hibiscus sabdariffa during pregnancy

“…This enzyme, therefore, is a key factor in limiting foetal exposure to maternal glucocorticoids. Its placental activity is regulated by nutritional and endocrine factors (Clarke et al, 2002;Seckl, 2001). Thus, it follows that increased foetal glucocorticoid exposure, therefore, occurs due to increased maternal glucocorticoid levels, decreased placental 11βOHSD-2 activity or increased glucocorticoid output by the foetal adrenal.…”

Chronic maternal stress inhibits the capacity to up-regulate placental 11β-hydroxysteroid dehydrogenase type 2 activity

“…Moreover, glucocorticoids can both up-and downregulate placental timing and mode of administration (Kerzner et al 2002, Ma et al 2003, van Beek et al 2004. Another study reported a reduction in ovine placental 11 -HSD2 activity in response to chronically elevated glucocorticoid levels (Clarke et al 2002). Importantly, none of the above studies investigated immediate regulation of placental 11 -HSD2 activity in response to glucocorticoids, although this presumably would be the most efficient way to inactivate stress-induced corticosteroids from maternal blood.…”

Glucocorticoid exposure and tissue gene expression of 11β HSD-1, 11β HSD-2, and glucocorticoid receptor in a porcine model of differential fetal growth

“…11b HSD-2 deactivates cortisol through conversion to the less active cortisone (Stewart et al 1995, Klemcke & Christenson 1996, Clarke et al 2002. Placental 11b HSD-2 is particularly important because maternal GC levels are up to tenfold higher than in the fetus, therefore, 11b HSD-2 acts to prevent placental diffusion of GC (Seckl 2001, Clarke et al 2002.…”

“…11b HSD-2 deactivates cortisol through conversion to the less active cortisone (Stewart et al 1995, Klemcke & Christenson 1996, Clarke et al 2002. Placental 11b HSD-2 is particularly important because maternal GC levels are up to tenfold higher than in the fetus, therefore, 11b HSD-2 acts to prevent placental diffusion of GC (Seckl 2001, Clarke et al 2002. Placental 11b HSD-2 is downregulated in response to maternal undernutrition, protein deficiency, reduced oxygen conditions, to chemicals such as glycyrrhizic acid and through mutation of the 11b HSD-2 gene (Dave-Sharma et al 1998, Bertram et al 2001, Alfaidy et al 2002.…”