ACTH is a Potent Regulator of Gene Expression in Human Adrenal Cells

Xing, Yewei; Parker, C Richard; Edwards, Michael; Rainey, William E

doi:10.1677/jme-10-0006

Cited by 83Adrenal Hormones and DisordersEstrogen and related hormone effectsHormonal Regulation and Hypertension

ACTH is a Potent Regulator of Gene Expression in Human Adrenal Cells

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Xing, Yewei, Parker, C Richard, Edwards, Michael, Rainey, William E·2010·Journal of Molecular Endocrinology

DOI 10.1677/jme-10-0006PMC PMC3725639

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Abstract

The adrenal glands are the primary source of minerocorticoids, glucocorticoids, and the so-called adrenal androgens. Under physiological conditions, cortisol and adrenal androgen synthesis are controlled primarily by ACTH. Although it has been established that ACTH can stimulate steroidogenesis, the effects of ACTH on overall gene expression in human adrenal cells have not been established. In this study, we defined the effects of chronic ACTH treatment on global gene expression in primary cultures of both adult adrenal (AA) and fetal adrenal (FA) cells. Microarray analysis indicated that 48 h of ACTH treatment caused 30 AA genes and 84 FA genes to increase by greater than fourfold, with 20 genes common in both cell cultures. Among these genes were six encoding enzymes involved in steroid biosynthesis, the ACTH receptor and its accessory protein, melanocortin 2 receptor accessory protein (ACTH receptor accessory protein). Real-time quantitative PCR confirmed the eight most upregulated and one downregulated common genes between two cell types. These data provide a group of ACTH-regulated genes including many that have not been previously studied with regard to adrenal function. These genes represent candidates for regulation of adrenal differentiation and steroid hormone biosynthesis.

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Like cortisol, 11-oxyandrogens are synthesized via the adrenal cortical enzyme 11β-hydroxylase (CYP11B1), which is regulated by ACTH.
“Like cortisol, 11-oxyandrogens are synthesized via the adrenal cortical enzyme 11β-hydroxylase (CYP11B1), which is regulated by ACTH (23).”
From 24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency (2021) · cites this paper as [23]
The Discussion (page unavailable) identifies CYP11B1 as a steroidogenic gene activated by ACTH and says the study confirmed its upregulation in human adrenal cells. It also links ACTH-upregulated enzymes to cortisol synthesis, but the paper does not address whether 11-oxyandrogens are synthesized via CYP11B1. (LLM, conf=0.86)
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The effects of ACTH on steroid metabolomic profiles in human adrenal cells
Xing, Y., Edwards, M. A., Ahlem, C., Kennedy, M., Cohen, A., Gomez-Sanchez, C. E., & Rainey, W. E. (2011) · Journal of Endocrinology · doi:10.1530/joe-10-0493 · Cited by 101 · see citing works
60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH
Gallo-Payet, N. (2016) · Journal of Molecular Endocrinology · doi:10.1530/jme-15-0257 · Cited by 98 · see citing works
ACTH-Dependent Ultradian Rhythm of Corticosterone Secretion
Spiga, F., Waite, E. J., Liu, Y., Kershaw, Y. M., Aguilera, G., & Lightman, S. L. (2011) · Endocrinology · doi:10.1210/en.2010-1209 · Cited by 97 · see citing works
Adrenocorticotropin Acutely Regulates Pregnenolone Sulfate Production by the Human Adrenal In Vivo and In Vitro
Rege, J., Nanba, A. T., Auchus, R. J., Ren, J., Peng, H.-M., Rainey, W. E., & Turcu, A. F. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01525 · Cited by 30 · see citing works
Self-citation
24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency
Turcu, A. F., Mallappa, A., Nella, A. A., Chen, X., Zhao, L., Nanba, A. T., Byrd, J. B., Auchus, R. J., & Merke, D. P. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.751191 · Cited by 20 · see citing works
“Like cortisol, 11oxyandrogens are synthesized via the adrenal cortical enzyme 11b-hydroxylase (CYP11B1), which is regulated by ACTH (23).”
Background
Establishment of a novel human fetal adrenal culture model that supports de novo and manipulated steroidogenesis
Melau, C., Nielsen, J. E., Perlman, S., Lundvall, L., Langhoff Thuesen, L., Juul Hare, K., Schou Hammerum, M., Frederiksen, H., Mitchell, R. T., Juul, A., et al. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa852 · Cited by 16 · see citing works

Interactions of adrenocorticotropic hormone with its adrenal receptors. Degradation of ACTH-1-24 and ACTH-11-24.
Saez, J. M., Dazord, A., Morera, A. M., et al. (1975) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)41747-x · Cited by 32 · see citing works
The Melanocortin-2 Receptor in Normal Adrenocortical Function and Familial Adrenocorticotropic Hormone Resistance
Clark, A. (2000) · Humana Press eBooks · doi:10.1007/978-1-59259-031-5_12 · Cited by 3 · see citing works
The adrenocorticotropic hormone receptor
Penhoat, A., Naville, D., & Bégeot, M. (2001) · Current Opinion in Endocrinology & Diabetes · doi:10.1097/00060793-200106000-00002 · Cited by 12 · see citing works
Adrenocorticotropic Hormone (ACTH) and ACTH Stimulation Test
Wård, L. (2022) · Laboratory Screening and Diagnostic Evaluation · doi:10.1891/9780826188434.0013
A monoclonal anti-peptide antibody recognizes the adrenocorticotropic receptor
Clarke, B. L., & Bost, K. L. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)91131-b · Cited by 7 · see citing works

Authors: Xing, Y., Parker, C. R., Edwards, M., & Rainey, W. E.
Affiliations: Augusta University (US)
University of Alabama at Birmingham (US)
Corresponding author: Rainey, William E
ORCID: Parker, C Richard
Edwards, Michael
Rainey, William E
Venue: Journal of Molecular Endocrinology
Publisher: Bioscientifica
Published: 2010-05-11
Volume: 45
Issue: 1
Pages: 59-68
ISSN: 0952-5041 (ISSN-L)
1479-6813
DOI: 10.1677/jme-10-0006
PMC: PMC3725639
OpenAlex: W2136707725
Cited by: 83
References: 77
Citations by year: 2026: 2 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 2 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 4 · 2017: 8 · 2016: 8 · 2015: 9 · 2014: 6 · 2013: 2 · 2012: 4
FWCI: 3.38
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Molecular Endocrinology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (DK069950, DK 43140, R01DK069950, R01DK043140)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD011149, HD-11149)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
Keywords: ACTH, gene expression regulation, adrenal cells, steroidogenesis, ACTH receptor, cortisol, adrenal androgens
MeSH terms: Adrenal Glands, Adrenocorticotropic Hormone, Adult, Animals, Cells, Cultured, Fetus, Humans, Molecular Sequence Data, Gene Expression, Gene Expression Profiling, Microarray Analysis

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ACTH is a Potent Regulator of Gene Expression in Human Adrenal Cells

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