Placental 11β‐hydroxysteroid dehydrogenase: a key regulator of fetal glucocorticoid exposure

TLDR

Placental 11β‑hydroxysteroid dehydrogenase (11β‑HSD) converts active cortisol to inactive cortisone and is thought to protect the fetus from growth‑retarding maternal glucocorticoids, although other placental enzymes may also contribute. The study aimed to clarify the role of 11β‑HSD by examining glucocorticoid metabolism in dual‑perfused freshly isolated intact human placentas. Freshly isolated term placentas were perfused with physiological cortisol, fetal effluent was collected, and steroid metabolites were separated by silica column chromatography and quantified by HPLC. The perfusion results showed that almost all maternal cortisol was metabolized to cortisone with no reverse conversion, and that inhibition of 11β‑HSD allowed cortisol to reach the fetus, confirming 11β‑.

Abstract

OBJECTIVE Placental 11β‐hydroxysteroid dehydrogenase (11β‐HSD), which converts active cortisol to inactive cortisone, has been proposed to be the mechanism guarding the fetus from the growth retarding effects of maternal glucocorticoids; however, other placental enzymes have also been implicated. Placental 11β‐HSD is unstable in vitro , and enzyme activity thus detected may not be relevant to the proposed barrier role. We have therefore examined placental glucocorticoid metabolism in dually perfused freshly isolated intact human placentas. DESIGN Placentas were obtained from randomly selected normal term deliveries. The maternal circuit was perfused with physiological concentration of cortisol, the fetal effluent collected and steroid metabolites separated and quantified using silica columns (Sep‐pak Plus) and HPLC. RESULTS Most of the maternally administered cortisol was metabolized to cortisone, and no conversion of cortisone to cortisol was detected. Cortisone was the only product of cortisol metabolism. Inhibition of 11β‐HSD with glycyrrhetinic acid allowed cortisol to gain direct access to the fetal circulation. CONCLUSION We conclude that human placental 11β‐HSD plays a crucial role in controlling glucocorticoid access to the fetus. Other enzymes are not significant contributors at physiologically relevant cortisol concentrations.