Multiple actions of synthetic ‘progestins’ on the growth of ZR-75-1 human breast cancer cells: Anin vitro model for the simultaneous assay of androgen, progestin, estrogen, and glucocorticoid agonistic and antagonistic activities of steroids

Poulin, Richard; Baker, Denis; Poirier, Donald; Labrie, Fernand

doi:10.1007/bf01806369

Cited by 73Estrogen and related hormone effectsProstate Cancer Treatment and ResearchBreast Cancer Treatment Studies

Multiple actions of synthetic ‘progestins’ on the growth of ZR-75-1 human breast cancer cells: Anin vitro model for the simultaneous assay of androgen, progestin, estrogen, and glucocorticoid agonistic and antagonistic activities of steroids

Poulin, Richard, Baker, Denis, Poirier, Donald, Labrie, Fernand·1991·Breast Cancer Research and Treatment

DOI 10.1007/bf01806369

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Abstract

This study was designed to assess the multiple steroid receptor mediated activities of a series of synthetic 'progestins' on breast cancer cell growth, using the human ZR-75-1 cell line which possesses functional estrogen (ER), androgen (AR), and glucocorticoid (GR) receptors as well as progesterone (PgR) receptors. Four 17-hydroxyprogesterone derivatives (chlormadinone acetate, CMA; cyproterone acetate, CPA; medroxyprogesterone acetate, MPA; and megestrol acetate, MGA) and two 19-nortestosterone derivatives (norethindrone, NRE, and norgestrel, NRG) were thus investigated. Based on the requirement of estrogens for PgR-mediated antiproliferative effects and the reversal of PgR-mediated action by insulin, it was found that although all 'progestins' could inhibit ZR-75-1 cell growth through the PgR at low concentrations, the relative contribution of this receptor in cell growth control is highly variable between compounds. The quantitative importance of PgR-mediated inhibition of cell proliferation was inversely related to the amplitude of the androgenic effects induced by the compounds, the AR-mediated effects increasing in the order CPA less than MGA less than CMA less than NRE less than NRG less than MPA. The specificity of these androgenic effects is further supported by their reversal upon addition of the antiandrogen hydroxyflutamide. In addition, the 17-hydroxyprogesterone derivatives, but not the 19-nortestosterone derivatives, had glucocorticoid activities at high (micromolar) concentrations, as shown by reversal of growth inhibition by the antagonist RU486 in the presence of saturating concentrations of 5 alpha-dihydro-testosterone. All 'progestins' tested, except MPA and NRE, also had some antiglucocorticoid activity, NRG being the most potent in this respect. Finally, NRE and NRG exerted a marked mitogenic effect in estrogen-free medium which was clearly mediated through the ER as shown by the competitive reversal of their action by the steroidal antiestrogen EM-139. The present results show that growth measurements of the human breast cancer cells ZR-75-1 permit, with the appropriate steroid additions, the assay of progestin, androgen, estrogen, and glucocorticoid agonistic as well as antagonistic activities of test compounds. The present study shows, somewhat surprisingly, that while the AR is almost completely responsible for the action of MPA at low concentrations, the majority of the action of NRE, NRG, and MGA is also exerted through AR, while the androgenic action of CPA plays a lower role in the growth inhibition induced by this compound.(ABSTRACT TRUNCATED AT 400 WORDS)

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MPA is a compound having progestational, glucocorticoid, and androgenic activities.
“As previously described, MPA is a compound having a complex series of activities, namely progestational, glucocorticoid, and androgenic (231).”
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 [231]
MPA exerts androgenic inhibitory effects on growth of human breast cancer cells in vitro.
“MPA has in fact been clearly shown to exert androgenic inhibitory effects on the growth of human breast cancer cells in vitro (209, 231, 245), thus suggesting the role of AR in the beneficial effects of MPA in breast cancer in women (246, 247).”
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 [231]

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Authors: Poulin, R., Baker, D., Poirier, D., & Labrie, F.
Affiliations: Université Laval (CA)
ORCID: Poirier, Donald
Venue: Breast Cancer Research and Treatment
Publisher: Springer Science and Business Media LLC
Published: 1991-01
Volume: 17
Issue: 3
Pages: 197-210
ISSN: 0167-6806 (ISSN-L)
1573-7217
DOI: 10.1007/bf01806369
OpenAlex: W1972218344
Cited by: 73
References: 59
Citations by year: 2022: 1 · 2019: 3 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 1
FWCI: 1.89
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Breast Cancer Research and Treatment (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Keywords: synthetic progestins, progesterone receptor, androgen receptor, estrogen receptor, glucocorticoid receptor, 19-nortestosterone derivatives, chlormadinone acetate, cyproterone acetate, medroxyprogesterone acetate, megestrol acetate, norethisterone, norgestrel, antiproliferative activity, mitogen response, hydroxyflutamide, RU486
MeSH terms: Binding, Competitive, Breast Neoplasms, Cell Division, Humans, Models, Biological, Receptors, Androgen, Receptors, Cell Surface, Receptors, Estrogen, Receptors, Glucocorticoid, Receptors, Progesterone, Tumor Cells, Cultured, Molecular Structure, Progesterone Congeners

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Multiple actions of synthetic ‘progestins’ on the growth of ZR-75-1 human breast cancer cells: Anin vitro model for the simultaneous assay of androgen, progestin, estrogen, and glucocorticoid agonistic and antagonistic activities of steroids

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