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Cited by 34Hormonal Regulation and HypertensionBirth, Development, and HealthAdrenal Hormones and Disorders

11β-Hydroxysteroid Dehydrogenase Type 2 and Mineralocorticoid Receptor in Human Fetal Development

Hirasawa, Gen, Sasano, Hironobu, Suzuki, Takashi, Takeyama, Junji, Muramatu, Yasunari, Fukushima, Kouhei, Hiwatashi, Nobuo, Toyota, Takayoshi +2 more·1999·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jcem.84.4.5615
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Abstract

11β-Hydroxysteroid dehydrogenase type II (11βHSD2) confers specificity on the mineralocorticoid receptor (MR) by converting biologically active glucocorticoids to inactive 11-keto metabolites. The biological significance of 11βHSD2 activity during fetal development is currently being explored, but the temporal and spatial distributions of the enzyme and receptor have not been examined. We therefore examined their distributions during various stages of human fetal development using immunohistochemistry. Both 11βHSD2 and MR immunoreactivity were detected in the distal convoluted and collecting tubules of the kidney from early in gestation. Fetal skin, intermediate layer of the epidermis, peridermal cells, and hair follicles were positive for both 11βHSD2 and MR. Weak 11βHSD2 and MR immunoreactivity was detected in the superficial ciliated epithelium of the esophagus, the deep layer of gastric epithelial cells, and the superficial epithelium of the small intestine. Columnar epithelium in the terminal bronchiolar budding component of fetal lung and tracheal and bronchial ciliated epithelium were also positive for MR and 11βHSD2 from early gestation. Colonic epithelium and pancreatic exocrine duct cells, which demonstrated marked immunoreactivity of both MR and 11βHSD2 in the adult, did not express MR and 11βHSD2 until very late in gestation. These results imply that mineralocorticoid action in the upper fetal gastrointestinal tract, kidney, skin, and lung is facilitated by 11βHSD2 and is involved in water and electrolyte transport between fetus and amniotic fluid as well as fetal urine production.

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  • 11βHSD2 prevents cortisol from overwhelming renal mineralocorticoid receptors, and in the placenta and other fetal tissues 11βHSD2 also inactivates cortisol.

    “Thus, 11␤HSD2 prevents cortisol from overwhelming renal mineralocorticoid receptors (569), and in the placenta and other fetal tissues 11␤HSD2 (583, 584) also inactivates cortisol.”

    From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [584]

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Authors
Hirasawa, G., Sasano, H., Suzuki, T., Takeyama, J., Muramatu, Y., Fukushima, K., Hiwatashi, N., Toyota, T., Nagura, H., & Krozowski, Z. S.
Affiliations
  • Departments of Pathology (G.H., H.S., T.S., J.T., Y.M., H.N.), Sendai, Japan
  • Tohoku University (JP)
  • Internal Medicine (G.H., N.H., T.T.), Sendai, Japan
  • Laboratory of Molecular Hypertension, Baker Medical Research Institute (Z.S.K.), Melbourne, Australia
Corresponding author
Hirasawa, Gen
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
1999-04-01
Volume
84
Issue
4
Pages
1453-1458
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jcem.84.4.5615
OpenAlex
W2073040994
Cited by
34
References
35
Citations by year
2021: 3 · 2019: 3 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 1 · 2012: 3
FWCI
0.68
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
11β-hydroxysteroid dehydrogenase type 2, mineralocorticoid receptor, human fetal development, fetal kidney, fetal skin, fetal lung, fetal gastrointestinal tract, fetal urine production, water and electrolyte transport, amniotic fluid, glucocorticoid metabolism, gestational development
MeSH terms
Female, Embryonic and Fetal Development, Fetus, Humans, Hydroxysteroid Dehydrogenases, Immunohistochemistry, Kidney, Liver, Lung, Pregnancy, Skin, Receptors, Mineralocorticoid, 11-beta-Hydroxysteroid Dehydrogenases

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