Ontogeny of 11β-Hydroxysteroid Dehydrogenase: Activity in the Placenta, Kidney, Colon of Fetal Rats and Rabbits

Mechanisms to regulate closely fetal GC exposure are of considerable importance, as certain organs (kidney, brain) are adversely affected by excess GCs. 11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) reduces transplacental passage of maternal GCs to the fetus. We hypothesized that 11β-HSD2, if active in fetal kidney and colon, might allow local tissue modulation of GC access during the critical last trimester. We determined the presence, ontogeny and functionality of 11β-HSD in the placenta and fetal, neonatal and adult kidney and colon in rats and rabbits and the cortisol:cortisone ratio in human amniotic fluid, which represents fetal urine. There was clear a 11β-HSD2 expression in last trimester fetal colon, kidney and placenta in both rats and rabbits. This appeared of functional importance, since the potency of cortisol on fetal rabbit colonic sodium flux in the Ussing chamber was increased by 11β-HSD inhibition. In human amniotic fluid, we found a decreasing ratio of cortisol:cortisone across the last trimester, suggesting an analogous onset of renal 11β-HSD2 activity in the human fetal kidney. Local fetal tissue 11β-HSD2 may modulate exposure to the deleterious effects of GCs upon target tissue maturation during sensitive periods of late gestation when fetal GC levels rise to prepare other organs (lung) for adaptations at birth.

Key words:

11 Beta Hydroxysteroid Dehydrogenase - Fetal Development - Kidney Enzymology - Colon Enzymology - Animal

References:

• 1 Ballard P L, Ballard R A. Scientific basis and therapeutic regimens for use of antenatal glucocorticoids.  Am J Obstet Gynecol. 1995;  173 254-262
• 2 Crowley P, Chalmers I, Keirse M J. The effects of corticosteroid administration before preterm delivery: an overview of the evidence from controlled trials.  Brit J Obstet Gynaecol. 1991;  97 11-25
• 3 Seckl J R. Glucocorticoids and small babies.  Q J Med. 1984;  87 259-262
• 4 Jobe A H. Single and repetitive maternal glucocorticoid exposures reduce fetal growth in sheep.  Am J Obstet Gynecol. 1998;  178 880-885
• 5 Edwards C R, Benediktsson R, Lindsay R S, Seckl J R. Dysfunction of placental glucocorticoid barrier: link between fetal environment and adult hypertension?.  Lancet. 1993;  341 355-357
• 6 Seckl J R. Glucocorticoids, feto-placental 11 beta-hydroxysteroid dehydrogenase type 2, and the early life origins of adult disease.  Steroids. 1997;  62 89-94
• 7 Nyirenda M J, Lindsay R S, Kenyon C J, Burchell A, Seckl J R. Glucocorticoid exposure in late gestation permanently programs rat hepatic phosphoenolpyruvate carboxykinase and glucocorticoid receptor expression and causes glucose intolerance in adult offspring.  J Clin Invest. 1998;  101 2174-2181
• 8 Ballard P L, Ballard R A, Gonzales L K, Huemmelink R, Wilson C M, Gross I. Corticosteroid binding by fetal rat and rabbit lung in organ culture.  J Steroid Biochem. 1984;  21 117-126
• 9 Lacobelli S, Ranelletti F, Sica G, Barile G. Glucocorticoid receptors in human fetal lung.  J Endocrinol Invest. 1978;  1 209-213
• 10 Fuller P J, Verity K. Mineralocorticoid receptor gene expression in the gastrointestinal tract: distribution and ontogeny.  J Steroid Biochem. 1990;  36 263-267
• 11 Diaz R, Brown R W, Seckl J R. Distinct ontogeny of glucocorticoid and mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase types I and II mRNAs in the fetal rat brain suggest a complex control of glucocorticoid actions.  J Neurosci. 1998;  18 2570-2580
• 12 Murphy B E. Human fetal serum cortisol levels related to gestational age: evidence of a midgestational fall and a steep late gestational rise, independent of sex or mode of delivery.  Am J Obstet Gynecol. 1982;  144 276-282
• 13 Dalle M. Perinatal changes in plasma and adrenalcorticosterone and aldosterone concentrations in the mouse.  J Endocrinol. 1978;  76 303-309
• 14 Dupouy J P. Maternal and foetal corticosterone levels during late pregnancy in rats.  J Endocrinol. 1975;  65 347-352
• 15 Cohen A. Adrenal and plasma corticosterone levels in the pregnant, foetal and neonatal rat, in the perinatal period.  Horm Metab Res. 1976;  8 474-478
• 16 Bernal A L, Flint A P, Anderson A B, Turnbull A C. 11 beta-Hydroxysteroid dehydrogenase activity (E.C. 1.1.1.146) in human placenta and decidua.  J Steroid Biochem. 1980;  13 1081-1087
• 17 Walker B R, Campbell J C, Williams B C, Edwards C R. Tissue-specific distribution of the NAD⁺-dependent isoform of 11 beta-hydroxysteroid dehydrogenase.  Endocrinology. 1992;  131 970-972
• 18 Lakshmi V, Monder C. Purification and characterization of the corticosteroid 11 beta-dehydrogenase component of the rat liver 11 beta-hydroxysteroid dehydrogenase complex.  Endocrinology. 1988;  123 2390-2398
• 19 Hierholzer K, Siebe H, Fromm M. Inhibition of 11 beta-hydroxysteroid dehydrogenase and its effect on epithelial sodium transport.  Kidney Int. 1990;  38 673-678
• 20 Albiston A L, Obeyesekere V R, Smith R E, Krozowski Z S. Clonint and tissue distribution of the human 11 beta-hydroxysteroid dehydrogenase type 2 enzyme.  Mol Cell Endocrinol. 1994;  105 R11-17
• 21 Funder J W. 11 beta-hydroxysteroid dehydrogenase and the meaning of life.  Mol Cell Endocrinol. 1990;  68 C3-5
• 22 Brown R W, Diaz R, Robson A C, Kotelevtsev Y V, Mullins J J, Kaufman M H, Seckl J R. The ontogeny of 11 beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor gene expression reveal intricate control of glucocorticoid action in development.  Endocrinology. 1996;  137 794-797
• 23 Stewart P M, Murry B A, Mason J I. Type 2 11 beta-hydroxysteroid dehydrogenase in human fetal tissues.  J Clin Endocrinol Metab. 1994;  78 1529-1532
• 24 Hundertmark S, Buhler H, Ragosch V, Dinkelborg L, Arabin B, Weitzel H K. Correlation of surfactant phosphatidylcholine synthesis and 11 beta-hydroxysteroid dehydrogenase in the fetal lung.  Endocrinology. 1995;  136 2573-2578
• 25 Hundertmark S, Ragosch V, Schein B, Buhler H, Fromm M, Lorenz U, Weitzel H K. 11-beta-hydroxysteroid dehydrogenase of rat lung:enzyme kinetic, oxidase-reductase ratio, electrolyte and trace element dependence.  Enzyme Protein. 1993;  47 83-91
• 26 Schoneshofer M. Urinary excretion rates of 15 free steroids: potential utility in differential diagnosis of Cushing’s syndrome.  Clin Chem. 1986;  32 93-96
• 27 Schoneshofer M. Automated liquid chromatographic determination of the 20-dihydro isomers of cortisol and corticosterone in human urine.  J Chromatogr. 1986;  380 267-274
• 28 Smith P K, Krohn R I, Hermanson G T, Mallia A K, Gartner F H, Provenzano M D, Fujimoto E K, Goeke N M, Olson B J, Klenk D C. Measurement of protein using bicinchoninic acid.  Analytical Biochemistry. 1985;  150 76-85
• 29 Brown R W, Chapman K E, Kotelevtsev Y, Yau J L, Lindsay R S, Brett L, Leckie C, Murad P, Lyons V, Mullins J J, Edwards C R, Seckl J R. Cloning and production of antisera to human placental 11 beta-hydroxysteroid dehydrogenase type 2.  Biochem J. 1996;  313 1007-1017
• 30 Naray-Fejes-Toth A, Fejes-Toth G. Expression cloning of the aldosterone target cell-specific 11 beta-hydroxysteroid dehydrogenase from rabbit collecting duct cells.  Endocrinology. 1995;  136 2579-2586
• 31 Alfaidy N, Blot Chabaud M, Robic D, Kenouch S, Bourbouze R, Bonvalet J P, Farman N. Characteristics and regulation of 11 beta-hydroxysteroid dehydrogenase of proximal and distal nephron.  Biochim Biophys Acta. 1995;  1243 461-468
• 32 Chailler P, Ferrari J, Briere N. Fetal mouse kidney maturation in vitro: coordinated influences of epidermal growth factor, transferrin and hydrocortisone.  Anat Embryol. 1991;  184 319-329
• 33 Avner E D, Piesco N P, Sweeney W E Jr, Studnicki F M, Fetterman G H, Ellis D. Hydrocortisone-induced cystic metanephric maldevelopment in serum-free organ culture.  Lab Invest. 1984;  50 208-218
• 34 Marandici A, Monder C. Inhibition by glycyrrhetinic acid of rat tissue 11 beta-hydroxysteroid dehydrogenase in vivo. .  Steroids. 1993;  58 153-156
• 35 Yang K. Placental 11 beta-hydroxysteroid dehydrogenase: barrier to maternal glucocorticoids.  Rev Reprod. 1997;  2 129-132
• 36 Benediktsson R, Calder A A, Edwards C R, Seckl J R. Placental 11 beta-hydroxysteroid dehydrogenase: a key regulator of fetal glucocorticoid exposure.  Clin Endocrinol. 1997;  46 161-166
• 37 Gewolb I H, Warshaw J B. Fetal and maternal corticosterone and corticosteroid binding globulin in the diabetic rat gestation.  Pediatr Res. 1986;  20 155-160
• 38 Bronshtein M, Amit A, Achiron R, Noy I, Blumenfeld Z. The early prenatal sonographic diagnosis of renal agenesis: techniques and possible pitfalls.  Prenat Diagn. 1994;  14 291-297
• 39 Best R, Walker B R. Additional value of measurement of urinary cortisone and unconjugated cortisol metabolites in assessing the activity of 11 beta-hydroxysteroid dehydrogenase in vivo. .  Clin Endocrinol. 1997;  47 231-236
• 40 Palermo M, Shackleton C H, Mantero F, Stewart P M. Urinary free cortisone and the assessment of 11 beta-hydroxysteroid dehydrogenase activity in man.  Clin Endocrinol. 1996;  45 605-611
• 41 Chelmicki Z. Level of cortisol in blood serum of maternal and umbilical cord during various methods of delivery.  Ginekol Pol. 1996;  67 283-286