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Progestin regulation of cellular proliferation.
Abstract
THE control of cellular proliferation is known to involve a delicate balance between the effects of different regulatory molecules including hormones and growth factors which provide, in the immediate environment of the cell, signals to stimulate or inhibit cellular replication (1). The past decade has seen significant progress in the identification and characterization of novel regulatory molecules, generally referred to as growth factors, and definition of their molecular mechanisms of action (2, 3). With the recent emphasis on peptide growth factors it is perhaps less well appreciated that some of the largest physiological changes (both positive and negative) in rates of growth and cell proliferation are mediated by steroid hormones. Recent studies on breast cancer cells (4) and immature rat uterus (5, 6), illustrating estrogenic control of autocrine and paracrine growth factor production, support the view that some of these steroid-induced responses are intimately linked to growth factor-mediated pathways although debate continues as to whether the growth factor response is the cause, or the consequence, of the estrogenic effect on cellular proliferation (7, 8). Generally speaking, the molecular mechanisms by which steroid hormones control proliferation are not well defined, with the most developed knowledge being in the area of estrogen action where a number of recent reviews are available (4, 9–11).
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“recent data suggest that progestins exert a negative impact on breast cancer (2-5), with recent reports indicating an increased risk of the disease in women (6,7).”
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“In rodents and humans, the UESCs undergo proliferation and differentiation into decidual cells in response to ovarian steroids and blastocyst implantation at the early stage of pregnancy (13, 15, 68).”
BackgroundSteroid hormone regulation of Clca3 expression in the murine uterus
Jeong, J.-W., Lee, K. Y., Lydon, J. P., et al. (2006) · Journal of Endocrinology · doi:10.1677/joe.1.06747 · Cited by 19
“The ovarian steroid hormone progesterone (P4) is an essential regulator of reproductive events associated with all aspects of the establishment and maintenance of pregnancy (Clarke & Sutherland 1990, Lydon et al. 1995).”
BackgroundExpression and Possible Role of 20.ALPHA.-Hydroxysteroid Dehydrogenase in the Placenta of the Goat
Jayasekara, W. S. N., Yonezawa, T., Ishida, M., Yamanouchi, K., & Nishihara, M. (2005) · Journal of Reproduction and Development · doi:10.1262/jrd.16074 · Cited by 19
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Expression of 67 kDa laminin receptor in human breast cancer cells: regulation by progestins
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BackgroundRational design of orally-active, pyrrolidine-based progesterone receptor partial agonists
Thompson, S. K., Washburn, D. G., Frazee, J. S., et al. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2009.06.055 · Cited by 17
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Adomaitienė, L., Nadišauskienė, R. J., Nickkho‐Amiry, M., Čižauskas, A., Palubinskienė, J., Holland, C. M., & Seif, M. W. (2019) · Medicina · doi:10.3390/medicina55090543 · Cited by 19
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Lin, V. C. L., Woon, C. T., Aw, S. E., et al. (2003) · Endocrinology · doi:10.1210/en.2003-0484 · Cited by 16
Involvement of 20.ALPHA.-Hydroxysteroid Dehydrogenase in the Maintenance of Pregnancy in Mice
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“For example, progesterone has inhibitory effects on the proliferation of several cell types [15].”
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Mouse models of uterine corpus tumors clinical significance and utility
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Hormone therapy and lung cancer mortality in women: Systematic review and meta-analysis
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“In general, progestogen can promote cell differentiation and regulate proliferation [32], which may assist in cancer survival.”
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Hormone replacement therapy and breast cancer
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Maldonado, V., Castilla, J. A., Martínez, L., et al. (2003) · Journal of Assisted Reproduction and Genetics · doi:10.1023/b:jarg.0000006710.64788.99 · Cited by 14
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BackgroundPrognostic role of sex steroid receptors in pancreatic adenocarcinoma
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“Estrogen promotes the proliferation of cells in the human endometrium while progesterone counteracts the growth-stimulatory effects of estrogen and induces glandular and stromal differentiation suitable for blastocyst implantation (Levy et al., 1980; Clarke and Sutherland, 1990; Ace and Okulicz, 1995).”
BackgroundMolecular Oncology of Breast Cancer
Ioan, A.-M., Klobocista, M. M., Shirazi, S., & Press, M. F. (2009) · Elsevier eBooks · doi:10.1016/b978-1-4160-5221-0.00028-0 · Cited by 13
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Progesterone regulates the proliferation of breast cancer cells – in vitro evidence
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“15–17 Progesterone, the dominant hormone of the luteal phase, impacts the growth inhibition of breast cancer, which should generate research attention.”
Immunolocalization of estrogen and progesterone receptors in ewe mammary glands
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Investigation of estrogen receptor α and β mRNA expression in the pregnant rat uterus
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Hormone-dependent placental manipulation of breast cancer cell migration
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“…by guest on 29 July 2018 progesterone on the breast cancer cell migration and cell-cycle phases is more controversial (Clarke and Sutherland, 1990; Sumida et al., 2004; Fu et al., 2008a,b; Zheng and Lin, 2008; Dressing and Lange, 2009; Fujita et al., 2010).”
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BackgroundProgesterone and the control of uterine cell proliferation and differentiation
Rider, V. (2002) · Frontiers in bioscience · doi:10.2741/rider · Cited by 12
Steroidal Regulation of Cell Cycle Progression
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Abortifacient potential of methanolic extract of Anthocephalus cadamba stem bark in mice
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“Progesterone plays an important role during ovulation, implantation and pregnancy (Clarke and Sutherland, 1990; Graham and Clarke, 1997).”
BackgroundSynthesis and SAR of amino acid-derived heterocyclic progesterone receptor full and partial agonists
Hammond, M., Patterson, J. R., Manns, S., et al. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2009.03.146 · Cited by 10
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“The majority of women (46 of 61) felt they could not tell that their period was coming (responses of 0–2); however, 15 felt that they could feel that their period would soon start [3,4].”
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The Progesterone Receptor/Estradiol Receptor Association and the Progestin-Triggered S-Phase Entry
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Rationale for Estrogen With Interrupted Progestin as a New Low-Dose Hormonal Replacement Therapy
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Role of Progesterone in the Control of Labor
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Sex Steroids and Their Influence in Lung Diseases Across the Lifespan
Borkar, N. A., & Sathish, V. (2021) · Physiology in health and disease · doi:10.1007/978-3-030-63549-7_3 · Cited by 10
“…is traditionally called the “pregnancy hormone,” but accumulating data have shown its physiological actions to affect several nonreproductive functions in both males and females (Clarke and Sutherland 1996; Lydon et al. 1996; Conneely and Lydon 2000; González-Orozco and Camacho-Arroyo 2019).”
BackgroundDiscovery of orally active, pyrrolidinone-based progesterone receptor partial agonists
Washburn, D. G., Hoang, T. H., Frazee, J. S., Johnson, L., Hammond, M., Manns, S., Madauss, K. P., Williams, S. P., Duraiswami, C., Tran, T. B., et al. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2009.06.081 · Cited by 9
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Effects of Expression of Exogenous Cyclin G1 on Proliferation of Human Endometrial Carcinoma Cells
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“Estrogen stimulates the proliferation of glandular cells, whereas progesterone inhibits their growth and induces secretory changes (4).”
BackgroundFocal adhesion kinase (FAK) involvement in human endometrial remodeling during the menstrual cycle.
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Effects of different progestogens on human breast tumor cell growth
Chen, F.-P., Chien, M., Chen, H.-Y., & Ng, Y. T. (2011) · Climacteric · doi:10.3109/13697137.2010.548565 · Cited by 8
Age at first birth and lung cancer: a two-sample Mendelian randomization study
Peng, H., Wu, X., Wen, Y., Du, X., Li, C., Liang, H., Lin, J., Liu, J., Ge, F., Huo, Z., et al. (2021) · Translational Lung Cancer Research · doi:10.21037/tlcr-20-1216 · Cited by 9
“It is well known that progesterone is capable to facilitate differentiation and inhibit cellular proliferation through the PR (86).”
Metadata
- Authors
- CLARKE, C. L., & SUTHERLAND, R. L.
- Affiliations
- Garvan Institute of Medical Research (AU)
- Corresponding author
- SUTHERLAND, ROBERT L.
- ORCID
- CLARKE, CHRISTINE L.
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 1990-05
- Volume
- 11
- Issue
- 2
- Pages
- 266-301
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- OpenAlex
- W2056357500
- Cited by
- 650
- References
- 0
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 4 · 2022: 9 · 2021: 7 · 2020: 5 · 2019: 7 · 2018: 6 · 2017: 10 · 2016: 12 · 2015: 18 · 2014: 12 · 2013: 15 · 2012: 21
- FWCI
- 10.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- progestins, cell proliferation, steroid hormones, growth factors, estrogen, breast cancer cells, immature uterus, autocrine and paracrine signaling, cell cycle regulation
- MeSH terms
- Animals, Haplorhini, Cell Division, Chickens, Humans, Progestins, Rabbits, Mice
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