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Profiling the Steroidogenic Pathway in Human Fetal and Adult Adrenals

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Abstract

Objective

Gene expression clearly underlies the marked structural and functional differences between the human fetal adrenal (HFA) and adult adrenal. We thus measured expression of steroidenic enzymes and associated cofactors in these tissues.

Methods

Real-time reverse transcriptase polymerase chain reaction was used to quantify transcripts encoding steroidogenic enzymes and the cofactors steroidogenic acute regulatory protein (StAR), cytochrome b5 (CYb5), and P450 oxidoreductase (POR).

Results

Cholesterol side-chain cleavage mRNA levels were 1.9-fold higher in the HFA than in the adult adrenal. Compared with a nonsignificant difference in 17α-hydroxylase/17,20 lyase mRNA abundance, CYb5 and POR were expressed 2.3-fold and 2.0-fold higher, respectively, in the HFA. Dehydroepiandrosterone (DHEA) sulfotransferase transcript (SULT2A1) was present at 13-fold higher levels in the HFA than the adult. 3β-Hydroxysteroid dehydrogenase type II (HSD3B2) mRNA was 127-fold higher in the adult adrenal. StAR, 21-hydroxylase, 11β hydroxylase, and aldosterone synthase mRNA abundance did not differ significantly.

Conclusion

In the HFA, increased mRNA for cholesterol side-chain cleavage reflects high cholesterol utilization for steroidogenesis. Both CYb5 and POR cofactors may up-regulate 17α-hydroxylase/17,20 lyase activity and thus DHEA sulfate production in the HFA. High levels of SULT2A1 mRNA reflect high DHEA sulfonation in the HFA and restricted expression in the adult. Lack of HSD3B2 in the HFA facilitates DHEA synthesis. The novel finding of high levels of 21-hydroxylase and 11β hydroxylase transcripts in the midgestational HFA merits further investigation. Thus different patterns of steroidogenic enzyme and cofactor gene expression might account for some of the phenotypic differences between the fetal and adult adrenal.

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Authors and Affiliations

  1. Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas, 75390-9032, USA

    Khurram S. Rehman MD, Bruce R. Carr MD & William E. Rainey PhD

Authors
  1. Khurram S. Rehman MD
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  2. Bruce R. Carr MD
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  3. William E. Rainey PhD
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Corresponding author

Correspondence to William E. Rainey PhD.

Additional information

Dedicated to Yasmin and Layla Rehman. The authors thank Louella Hupp for editorial assistance and Bobbie Mayhew for technical support.

Supported by NIH grant numbers T32 HD07190 and R01 DK043140.

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Rehman, K.S., Carr, B.R. & Rainey, W.E. Profiling the Steroidogenic Pathway in Human Fetal and Adult Adrenals. Reprod. Sci. 10, 372–380 (2003). https://doi.org/10.1016/S1071-5576(03)00118-7

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