Modulation of growth, differentiation and carcinogenesis by dehydroepiandrosterone.

Gordon, Gary B.; Shantz, Lisa M.; Talalay, Paul

doi:10.1016/0065-2571(87)90023-9

Cited by 159Estrogen and related hormone effectsMetabolism, Diabetes, and CancerAdrenal Hormones and Disorders

Modulation of growth, differentiation and carcinogenesis by dehydroepiandrosterone.

Gordon, Gary B., Shantz, Lisa M., Talalay, Paul·1987·Advances in Enzyme Regulation

DOI 10.1016/0065-2571(87)90023-9

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Abstract

Dehydroepiandrosterone (3 beta-hydroxy-5-androsten-17-one; DHEA) and its conjugates are abundant circulating steroids that originate largely from the adrenal cortex. Their levels decline profoundly with age in human beings of both sexes, as the incidence of most cancers rises. Low levels of these steroids have been associated with the presence and risk of development of cancer. Administration of DHEA to rodents produces protection against spontaneous tumors and chemical carcinogenesis, suppresses weight gain without significantly affecting food intake, ameliorates the severity of diabetes in genetically diabetic mice, and restrains autoimmune processes. DHEA and related steroids also depress the mitogenic effects of carcinogens, tumor promoters and plant lectins, and block viral and carcinogen-induced cell transformations. DHEA and certain congeners are also potent and quite specific inhibitors of mammalian glucose-6-phosphate dehydrogenases. We have observed that the conversion of 3T3-L1 and 3T3-F442A preadipocyte clones to the adipocyte phenotype, in response to appropriate differentiation stimuli (fetal calf serum, insulin, dexamethasone, and 1-methyl-3-isobutylxanthine), is blocked by DHEA and other steroidal inhibitors of glucose-6-phosphate dehydrogenase. The structural requirements for blocking adipocyte differentiation and for inhibiting glucose-6-phosphate dehydrogenase are closely correlated. Evidence is reviewed suggesting that the inhibition of glucose-6-phosphate dehydrogenase is central to the anticarcinogenic and differentiation-blocking actions of DHEA and related steroids. The 3T3 preadipocyte clones provide a valuable system for the analysis of the mechanisms of the effects of DHEA on growth, differentiation and carcinogenesis.

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A series of studies in experimental animals have shown anticarcinogenic activity of DHEA.
“A series of studies performed in experimental animals have shown the anticarcinogenic activity of DHEA (258, 286, 287).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [286]

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Authors: Gordon, G. B., Shantz, L. M., & Talalay, P.
Affiliations: Johns Hopkins University (US)
ORCID: Shantz, Lisa M.
Venue: Advances in Enzyme Regulation
Publisher: Elsevier BV
Published: 1987-01
Volume: 26
Pages: 355-382
ISSN: 0065-2571 (ISSN-L)
DOI: 10.1016/0065-2571(87)90023-9
OpenAlex: W2011411875
Cited by: 159
References: 89
Citations by year: 2025: 1 · 2023: 2 · 2019: 1 · 2018: 2 · 2016: 1 · 2015: 2 · 2013: 1 · 2012: 1
FWCI: 4.61
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Advances in Enzyme Regulation (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (AM-07422)
National Cancer Institute (5T32 CA 90243)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords: dehydroepiandrosterone, adipogenesis, 3T3-L1 preadipocytes, 3T3-F442A preadipocytes, anticarcinogenic activity, chemical carcinogenesis, cell transformation, mitogen response, aging and cancer risk
MeSH terms: Adipose Tissue, Animals, Body Weight, Cell Differentiation, Cell Division, Dehydroepiandrosterone, Diabetes Mellitus, Experimental, Female, Humans, Male, Neoplasms, Neoplasms, Experimental, Steroids, Mice, Rats

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Modulation of growth, differentiation and carcinogenesis by dehydroepiandrosterone.

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