Endogenous C19-steroids and oestradiol levels in human primary breast tumour tissues and their correlation with androgen and oestrogen receptors
Abstract
Endogenous levels of testosterone, 5 alpha-dihydrotestosterone (5 alpha-DHT), androstenedione and oestradiol as well as levels of androgen (AR) and oestrogen (ER) receptors were measured in human primary breast tumour samples. The purification procedure developed allowed simultaneous quantitation of the four steroids, by radioimmunoassay, in small samples with adequate precision, sensitivity and accuracy. The majority of the tumours analysed contained detectable levels of the four steroids in the homogenate or cytosol fractions. There was no significant correlation between steroid content of the tissue and the age of the patient for any of the four steroids. A positive correlation (r = 0.71) was found between the levels of 5 alpha-DHT and testosterone in tumours. In general, tissue steroid concentrations decreased with an increase in dedifferentiation. Fifty-two per cent of the tumours analysed for receptor content were found to be ER positive, and a similar proportion were AR positive. No relationship was observed between AR status and age although receptor concentration was significantly (P = 0.004) higher in post-menopausal women when only receptor positive tumours were evaluated. The mean values for AR and ER were higher in tumours containing both receptors than in tumours showing either receptor alone; there was, however, no significant relationship between concentrations of the two receptors. No correlation was observed between tumour AR or ER status and any of the four steroids measured in either fraction. In addition, the ratio between the combined levels of 5 alpha-DHT and testosterone compared to oestradiol in the same tumour, only showed a maximum value of 40. Thus, in vivo these two androgens are unlikely to influence oestrogen action in human primary breast tumours by interfering with the association of oestradiol with its receptor.
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4-Dione also led to significant growth inhibition in ZR-75-1 cells, although the active concentrations (IC50, 15 nM) are in the upper range of the plasma concentrations (1-10 nM) found in women.
“4-Dione also led to significant growth inhibition in ZR-75-1 cells, although the active concentrations (IC 50 , 15 nm) are in the upper range of the plasma concentrations (1-10 nm) found in women (215-218).”
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 [218]
In ZR-75-1 cells, concentrations of DHT in the incubation medium similar to the plasma levels found in normal women and breast cancer patients (0.3-0.7 nM) are potent inhibitors of the mitogenic effect of E2 and even inhibit growth in the absence of estrogens.
“In ZR-75-1 cells, concentrations of DHT in the incubation medium similar to the plasma levels found in normal women (215-217) and breast cancer patients (Ref.218; 0.3-0.7 nm) are potent inhibitors of the mitogenic effect of E 2 and even inhibit growth in the absence of estrogens (208).”
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 [218]
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- Authors
- Mistry, P., Griffiths, K., & Maynard, P. V.
- Affiliations
- Brunel University of London (GB)
- Tenovus Cancer Care (GB)
- Queen's Medical Centre (GB)
- Corresponding author
- Mistry, Prakash
- ORCID
- Griffiths, Keith
- Venue
- Journal of Steroid Biochemistry
- Publisher
- Elsevier BV
- Published
- 1986-06
- Volume
- 24
- Issue
- 6
- Pages
- 1117-1125
- ISSN
- 0022-4731 (ISSN-L)
- OpenAlex
- W2085016459
- Cited by
- 34
- References
- 46
- Citations by year
- 2018: 2 · 2014: 1 · 2012: 2
- FWCI
- 0.25
- 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 › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Keywords
- breast cancer, endogenous steroids, testosterone, dihydrotestosterone, androstenedione, estradiol, androgen receptor, oestrogen receptor, tumor dedifferentiation, postmenopausal women, steroid quantitation
- MeSH terms
- Adult, Aged, Androgens, Androstenedione, Breast Neoplasms, Estradiol, Female, Humans, Menopause, Middle Aged, Radioimmunoassay, Receptors, Androgen, Receptors, Estrogen, Dihydrotestosterone, Testosterone
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