The metabolism of androstenedione and testosterone to C19 metabolites in normal breast, breast carcinoma and benign prostatic hypertrophy tissue
Abstract
In previous studies from our laboratory of the metabolism of androstenedione (A) and testosterone (T) in breast adipose and breast carcinoma tissue, the aromatization of these compounds, and their interconversion were demonstrated. The present study describes the conversion of androstenedione and testosterone to C19 metabolites in homogenates of normal breast tissue and breast carcinoma tissue and examines the C19 metabolites in homogenates of benign prostatic hypertrophy (BPH) tissue under similar conditions. Tissue homogenates were incubated for 90 min in Krebs-Ringer bicarbonate buffer (pH 7.4) with ATP (3 mM) and NADPH (2.4 mM) as co-factors. Following extraction with ethyl acetate, the metabolites were separated into neutral and phenolic fractions. Identification of specific products was made by thin layer and paper chromatography and recrystallization procedures. The formation of C19 metabolites was 10-fold greater in prostate than in breast tissue. Androsterone was the major product of androstenedione in both breast and prostate. The other 5 alpha-metabolites of androstenedione identified were dihydrotestosterone (DHT) and epiandrosterone (EPI). The 5 beta-metabolite, etiocholanolone (ET10), was identified in both breast and prostate following incubation with androstenedione. Using testosterone as substrate, dihydrotestosterone was the major product in normal breast and BPH. Etiocholanolone was detected in breast, but not in prostate following incubation with testosterone. Aromatization was demonstrated in all incubations with breast tissue, but not in prostate. The results indicate that androstenedione is actively metabolized by both breast and prostate to 5 alpha reduced metabolites. They also identify the formation of etiocholanolone in both tissues. Aromatization was demonstrated only in breast tissue.
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The ability of 4-dione to induce an antiproliferative effect (IC50, ~15 nM) most likely results from its metabolic transformation into testosterone and DHT than from its direct interaction with the AR (KD, ~200 nM).
“The ability of 4-dione to induce an antiproliferative effect (IC 50 , ϳ15 nm) most likely results from its metabolic transformation into testosterone and DHT (223-225) than from its direct interaction with the AR (K D , ϳ200 nm).”
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 [225]
Cites
Ovarian and adrenal contribution to peripheral androgens during the menstrual cycle
ABRAHAM, G. E. (1974) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-39-2-340 · Cited by 436 · see citing works
Aromatization of Androgens by Muscle and Adipose Tissue in Vivo*
LONGCOPE, C., PRATT, J. H., STEPHEN, H. S., & FINEBERG, S. E. (1978) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-46-1-146 · Cited by 392 · see citing works
CONVERSION OF ANDROSTENEDIONE TO ESTRONE BY HUMAN FAT TISSUE
Schindler, A. E., Ebert, A., & Friedrich, E. (1972) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-35-4-627 · Cited by 319 · see citing works
Drugs and the heart. V. Digitalis and sympathomimetic stimulants.
Opie, L. H. (1980) · PubMed · Cited by 172 · see citing works
Hammond, G. L. (1978) · Journal of Endocrinology · doi:10.1677/joe.0.0780007 · Cited by 145 · see citing works
The interconversion and aromatization of androgens by human adipose tissue
Perel, E., & KILLINGER, D. W. (1979) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(79)90514-4 · Cited by 144 · see citing works
Self-citationAromatization of Androstenedione by Isolated Human Hairs
SCHWEIKERT, H. U., MILEWICH, L., & WILSON, J. D. (1975) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-40-3-413 · Cited by 135 · see citing works
The conversion of androstenedione to estrone, estradiol, and testosterone in breast tissue
Perel, E., Wilkins, D., & KILLINGER, D. W. (1980) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(80)90117-x · Cited by 124 · see citing works
Self-citationKrieg, M., BARTSCH, W., Janssen, W., & Voigt, K. (1979) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(79)90090-6 · Cited by 117 · see citing works
Levere, R. D., Kappas, A., & Granick, S. (1967) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.58.3.985 · Cited by 108 · see citing works
Catabolism of [4-14C]testosterone by subcellular fractions of human prostate
Chamberlain, J., Jagarinec, N., & Ofner, P. (1966) · Biochemical Journal · doi:10.1042/bj0990610 · Cited by 89 · see citing works
Metabolism of Testosterone by the Human Prostate
Farnsworth, W. E. (1963) · JAMA · doi:10.1001/jama.1963.63700060003011a · Cited by 80 · see citing works
Steroid metabolism by human breast and rat mammary carcihomata
Miller, W. R. (1974) · Steroids · doi:10.1016/0039-128x(74)90089-0 · Cited by 71 · see citing works
Short Communications. Steroid metabolism by human breast tumours
Jones, D. A., Cameron, E. H. D., Griffiths, K., et al. (1970) · Biochemical Journal · doi:10.1042/bj1160919 · Cited by 68 · see citing works
An Antiestrogenic Action of Androgens in Human Breast Cancer Cells*
MacIndoe, J. H., & Etre, L. A. (1981) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-53-4-836 · Cited by 54 · see citing works
Steroid metabolism by human mammary carcinoma
Li, K., Chandra, D. P., Foo, T. M. S., et al. (1976) · Steroids · doi:10.1016/0039-128x(76)90024-6 · Cited by 51 · see citing works
SLUITER, H. J. (1975) · The Lancet · doi:10.1016/s0140-6736(75)90600-5 · Cited by 47 · see citing works
THE INFLUENCE OF OESTRADIOL ON THE METABOLISM OF ANDROGENS BY HUMAN PROSTATIC TISSUE
BARD, D. R., & Lasnitzki, I. (1977) · Journal of Endocrinology · doi:10.1677/joe.0.0740001 · Cited by 33 · see citing works
METABOLISM OF ANDROGENS BY HUMAN BREAST TISSUE
Miller, W. R., Mcdonald, D., Forrest, A. P. M., et al. (1973) · The Lancet · doi:10.1016/s0140-6736(73)91363-9 · Cited by 32 · see citing works
Failure of human benign prostatic hyperplasia to aromatise testosterone
Smith., T., CHISHOLM, G. D., & Habib, F. K. (1982) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(82)90601-x · Cited by 31 · see citing works
METABOLISM OF TESTOSTERONE BY HUMAN BREAST TUMOURS
Jenkins, J. S., & Ash, S. (1972) · The Lancet · doi:10.1016/s0140-6736(72)91907-1 · Cited by 30 · see citing works
Metabolism of 19-nortestosterone by human prostate
Farnsworth, W. E. (1966) · Steroids · doi:10.1016/0039-128x(66)91012-9 · Cited by 28 · see citing works
Mori, M., Tominaga, T., & Bun-Ichi, T. (1978) · Endocrinology · doi:10.1210/endo-102-5-1387 · Cited by 27 · see citing works
Androgen metabolism in male and female breast tissue
Perel, E., Davis, S., & KILLINGER, D. W. (1981) · Steroids · doi:10.1016/s0039-128x(81)90314-7 · Cited by 23 · see citing works
Self-citationLasnitzki, I. (1979) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(79)90091-8 · Cited by 19 · see citing works
Steroid metabolism in human breast cancer cell lines
Raju, U. (1978) · Steroids · doi:10.1016/0039-128x(78)90077-6 · Cited by 18 · see citing works
Hormone Metabolism and Action: II. Androstenedione in Prostate Organ Culture
Roy, A. K., Baulieu, É.-É., Feyel-Cabanes, T., et al. (1972) · Endocrinology · doi:10.1210/endo-91-2-396 · Cited by 17 · see citing works
Studies on steroid metabolism in human prostatic tissue
Collins, W. P., KOULLAPIS, E. N., Bridges, C., et al. (1970) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(70)90015-4 · Cited by 14 · see citing works
Factors affecting testosterone metabolism by human breast tissues.
Wr, M., Shivas, A. A., & Forrest, A. P. (1978) · PubMed · Cited by 13 · see citing works
Cowan, R. A., Sheila, B. C., Cowan, K., et al. (1979) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(79)90089-x · Cited by 12 · see citing works
C19O2-steroid transformations in the human normal, hyperplastic and cancerous prostate
Morfin, R., Charles, J. F., & Floch, H. H. (1979) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(79)90088-8 · Cited by 11 · see citing works
The Metabolism and 24-Hour Plasma Concentrations of Androsterone in Man
HELLMAN, L., Kream, J., & Rosenfeld, R. S. (1977) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-45-1-35 · Cited by 7 · see citing works
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Labrie, F., Luu-The, V., Labrie, C., Bélanger, A., Simard, J., Lin, S.-X., & Pelletier, G. (2003) · Endocrine Reviews · doi:10.1210/er.2001-0031 · Cited by 544 · see citing works
Poulin, R., Baker, D., & Labrie, F. (1988) · Breast Cancer Research and Treatment · doi:10.1007/bf01805942 · Cited by 172 · see citing works
Perel, E., Daniilescu, D., Kharlip, L., Blackstein, M. E., & Killinger, D. W. (1985) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(85)90023-1 · Cited by 17 · see citing works
Self-citation
- Authors
- Perel, E., & Killinger, D. W.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Killinger, D.W.
- Venue
- Journal of Steroid Biochemistry
- Publisher
- Elsevier BV
- Published
- 1983-08
- Volume
- 19
- Issue
- 2
- Pages
- 1135-1139
- ISSN
- 0022-4731 (ISSN-L)
- OpenAlex
- W2077118870
- Cited by
- 33
- References
- 32
- Citations by year
- 2022: 1 · 2017: 1
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Steroid Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- 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
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Keywords
- androstenedione, testosterone, aromatization, androsterone, dihydrotestosterone, epiandrosterone, etiocholanolone, 5α-reduction, breast cancer, benign prostatic hyperplasia, breast tissue, prostate tissue, steroid metabolism
- MeSH terms
- Androstenedione, Androsterone, Breast, Breast Neoplasms, Etiocholanolone, Female, Humans, Male, Prostatic Hyperplasia, Dihydrotestosterone, Testosterone
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