Type 2 11 beta-hydroxysteroid dehydrogenase in human fetal tissues

Area of Science:

• Endocrinology
• Developmental Biology
• Biochemistry

Background:

• 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) regulates cortisol activity, crucial for mineralocorticoid and glucocorticoid receptor access.
• Two isoforms, type 1 (NADP(H)-dependent) and type 2 (NAD-dependent), have been identified.
• Fetal 11 beta-HSD activity may protect developing tissues from cortisol excess or modulate glucocorticoid actions.

Purpose of the Study:

• To investigate 11 beta-HSD activity and mRNA expression in human mid-gestational fetal tissues.
• To determine the specific isoforms present and their distribution.
• To understand the role of 11 beta-HSD in fetal development.

Main Methods:

• Incubation of fetal tissue homogenates with cortisol or cortisone using NAD or NADP cofactors.
• Assay of 11 beta-HSD activity via conversion rates.
• Northern blot analysis and RT-PCR to detect 11 beta-HSD mRNA transcripts.

Main Results:

• 11 beta-HSD type 1 activity and mRNA were undetectable in fetal tissues but present in maternal decidua.
• 11 beta-HSD type 2 activity was ubiquitous in fetal tissues, with highest levels in kidney, lung, gonad, liver, and colon.
• Activity studies confirmed type 2 as the predominant isoform mediating cortisol to cortisone conversion in fetal tissues.

Conclusions:

• Fetal 11 beta-HSD activity is primarily mediated by the high-affinity type 2 isoform.
• The widespread distribution of type 2 11 beta-HSD suggests a significant role in human fetal development.
• Type 1 11 beta-HSD expression likely occurs later in gestation or postnatally.