Profiling transcript levels for steroidogenic enzymes in fetal tissues
Abstract
Cytochrome P450 (CYP) and hydroxysteroid dehydrogenase enzymes are involved in the conversion of cholesterol to steroid hormones. These enzymes are primarily expressed in the placenta, adrenal and gonads. Interestingly, some of these enzyme activities have been demonstrated in non-endocrine tissues, where they may be involved in important paracrine and autocrine actions. This is particularly the case in the human fetus where steroid precursors circulate at high levels and could be metabolized within tissues to produce active steroid hormones. Herein, we tested the hypothesis that transcripts for steroidogenic enzymes are expressed in fetal tissues other than the classical steroidogenic organs. To test this hypothesis, real-time reverse transcription polymerase chain reaction (RT-RTPCR) assays were developed that quantify mRNA levels for steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage (CYP11A), 3beta-hydroxysteroid dehydrogenase types 1 and 2 (HSD3B1 and HSD3B2), 17alpha-hydroxylase (CYP17), 21-hydroxylase (CYP21), 11beta-hydroxylase (CYP11B1), aldosterone synthase (CYP11B2) and aromatase (CYP19). The use of RT-RTPCR allows the specific detection of these transcripts at levels that would not be detectable using northern analysis. In addition, this method can detect levels of transcript that would not lead to sufficient protein for detection of enzymatic activity of protein by western analysis. Thus, this methodology can detect low levels of expression that could play a role in regulating intra-tissue concentrations of steroid hormone. Total RNAs used for RT-RTPCR analysis were isolated from several human fetal tissues, including adrenal, testis, ovary, placenta, aorta, brain, liver, kidney, heart, lung, pancreas, prostate, stomach, and thymus. Our findings suggest that RT-RTPCR is a powerful tool for the examination of steroidogenic enzyme mRNA expressions. Using this approach, we have identified and quantified transcript levels of StAR and steroidogenic enzymes in several endocrine and non-endocrine fetal tissues. Even though some of the mRNA levels measured in these peripheral tissues are extremely lower in respect to the steroidogenic tissues, they could be sufficient to produce local (i.e. autocrine and paracrine) effects because produced steroids are not diluted into the entire circulation. These findings open new perspectives on the role of steroid hormones synthesized locally as probable regulatory factors of the development of several organ systems.
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CYP17A1 is expressed in many fetal tissues, but with the exception of the adrenal and testis, transcript levels are low, suggesting enzyme activity is also probably low.
“CYP17A1 is expressed in many fetal tissues [30] but, with the exception of the adrenal and testis, transcript levels are low ([30] and this study), suggesting enzyme activity is also probably low.”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [30]
HSD3B2 activity is likely to be relatively low compared with CYP17A1 in both adrenal and testis, based on transcript levels.
“In addition, HSD3B2 activity is likely to be relatively low compared with CYP17A1 in both tissues, based on transcript levels (this study and [28–30]).”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [30]
Several other human fetal tissues express CYP11A1 and may be capable of pregnenolone synthesis, but based on transcript levels, they are likely to make a minor overall contribution to plasma levels.
“Several other human fetal tissues express CYP11A1 and may be capable of pregnenolone synthesis [30] but, based on transcript levels, they are likely to make a minor overall contribution to plasma levels.”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [30]
Two isoforms of CYP11B are expressed in zona glomerulosa, both with ability to catalyze 11β-hydroxylation of DOC yielding corticosterone.
“Two isoforms of CYP11B are expressed in the zona glomerulosa, both with the ability to catalyze the 11β-hydroxylation of DOC yielding corticosterone.”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [26]
In adrenal zona glomerulosa, CYP11A1 converts cholesterol to pregnenolone, followed by HSD3B2-catalyzed conversion of pregnenolone to progesterone.
“CYP11A1 converts cholesterol to pregnenolone, followed by the HSD3B2-catalyzed conversion of pregnenolone to the Δ4 steroid, progesterone.”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [26]
Progesterone is converted to 11-deoxycorticosterone (DOC) by CYP21A2, which is abundantly expressed in ER of zona glomerulosa.
“Progesterone is subsequently converted to 11-deoxycorticosterone (DOC) by CYP21A2, which is abundantly expressed in the ER of the zona glomerulosa [26,27].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [26]
HSD3B2 is present in both mitochondria and ER of zona glomerulosa cells.
“HSD3B2 is present in both the mitochondria and ER of zona glomerulosa cells [25,26].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [26]
CYP11B2 (aldosterone synthase) exhibits 18-hydroxylase and 18-methyl oxidase activity required to convert corticosterone to aldosterone via 18-hydroxycorticosterone intermediate.
“CYP11B2, which is also known as aldosterone synthase, additionally exhibits 18-hydroxylase and 18-methyl oxidase activity, which are required to convert corticosterone to aldosterone via the 18-hydroxycorticosterone intermediate [26,28,29].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [26]
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- Authors
- Pezzi, V., Mathis, J. M., Rainey, W. E., & Carr, B. R.
- Affiliations
- University of Calabria (IT)
- Louisiana State University Health Sciences Center Shreveport (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Carr, Bruce R
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 87
- Issue
- 2-3
- Pages
- 181-189
- ISSN
- 0960-0760 (ISSN-L)
- OpenAlex
- W2040941219
- Cited by
- 156
- References
- 44
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 8 · 2020: 5 · 2019: 8 · 2018: 8 · 2017: 4 · 2016: 10 · 2015: 4 · 2014: 4 · 2013: 3 · 2012: 10
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Archive of Doctoral Theses and Digital Collections (University of Calabria) (submittedVersion)
- Funders
- Centre National de la Recherche Scientifique
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-37867, DK 43140)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Keywords
- steroidogenic enzymes, fetal tissue, steroidogenesis, steroidogenic acute regulatory protein, CYP11A, HSD3B1, HSD3B2, CYP17, CYP21, CYP11B1, CYP11B2, aromatase, mRNA expression profiling
- MeSH terms
- Steroidogenic Acute Regulatory Protein, Cytochrome P-450 Enzyme System, Fetus, Humans, Phosphoproteins, RNA, Messenger, 3-Hydroxysteroid Dehydrogenases, Oligonucleotide Probes, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Developmental, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling
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