Download PDF
Horm Metab Res 2001; 33(2): 78-83
DOI: 10.1055/s-2001-12429
Original Basic

© Georg Thieme Verlag Stuttgart · New York

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

S. Hundertmark1 , H. Bühler1 , M. Fromm2 , V. Ragosch1 , K. Kuhlmann1 , J. R. Seckl3
  • 1 Department of Obstetrics and Gynecology, Freie Universität Berlin, Germany
  • 2 Department of Clinical Physiology, Freie Universität Berlin, Germany
  • 3 Molecular Medicine Centre, The University of Edinburgh Western General Hospital, Edinburgh, UK
Further Information

Publication History

Publication Date:
31 December 2001 (online)

Also available at
    Permissions and Reprints

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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 3 Seckl J R. Glucocorticoids and small babies.  Q J Med. 1984;  87 259-262
    PubMedGoogle Scholar
  • 4 Jobe A H. Single and repetitive maternal glucocorticoid exposures reduce fetal growth in sheep.  Am J Obstet Gynecol. 1998;  178 880-885
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    Google Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 9 Lacobelli S, Ranelletti F, Sica G, Barile G. Glucocorticoid receptors in human fetal lung.  J Endocrinol Invest. 1978;  1 209-213
    PubMedGoogle Scholar
  • 10 Fuller P J, Verity K. Mineralocorticoid receptor gene expression in the gastrointestinal tract: distribution and ontogeny.  J Steroid Biochem. 1990;  36 263-267
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 13 Dalle M. Perinatal changes in plasma and adrenalcorticosterone and aldosterone concentrations in the mouse.  J Endocrinol. 1978;  76 303-309
    PubMedGoogle Scholar
  • 14 Dupouy J P. Maternal and foetal corticosterone levels during late pregnancy in rats.  J Endocrinol. 1975;  65 347-352
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 21 Funder J W. 11 beta-hydroxysteroid dehydrogenase and the meaning of life.  Mol Cell Endocrinol. 1990;  68 C3-5
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 34 Marandici A, Monder C. Inhibition by glycyrrhetinic acid of rat tissue 11 beta-hydroxysteroid dehydrogenase in vivo. .  Steroids. 1993;  58 153-156
    CrossrefPubMedGoogle Scholar
  • 35 Yang K. Placental 11 beta-hydroxysteroid dehydrogenase: barrier to maternal glucocorticoids.  Rev Reprod. 1997;  2 129-132
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar

Dr. S. Hundertmark

Frauenklinik und Poliklinik
Klinikum Benjamin Franklin der Freien Universität Berlin

Hindenburgdamm 30
12200 Berlin
Germany


Phone: Phone:+ 49 (30) 8445-2593

Fax: Fax:+ 49 (30) 8445-4477

Email: E-mail:hundertmark@ukbf.fu-berlin.de