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 progestins exert a negative impact on breast cancer, with recent reports indicating an increased risk of the disease in women.
“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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“Accumulated evidence has indicated that progestins are also involved in controlling mammary tumorigenesis (Kiss et al., 1986; Braunsberg et al., 1987; Manni et al., 1987; Clarke and Sutherland, 1990; Groshong et al., 1997; Lange et al., 1998).”
BackgroundEstrogen and Progestin Regulation of Cell Cycle Progression
Sutherland, R. L., Prall, O. W. J., Watts, C. K. W., & Musgrove, E. A. (1998) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1023/a:1018774302092 · Cited by 116 · see citing works
“Although progestins both stimulate and inhibit breast in inducing increased growth rates in cells that are already proliferating at near maximal rates in serumepithelial cell proliferation in vitro the predominant effect is growth inhibition (5,11).”
BackgroundInfluentialSelf-citationWiebe, J. P., Muzia, D., Hu, J. J., Szwajcer, D., Hill, S. A., & Seachrist, J. L. (2000) · PubMed · Cited by 114 · see citing works
Progesterone Enhances Interleukin-15 Production in Human Endometrial Stromal Cells in Vitro1
Okada, H., Nakajima, T., Sanezumi, M., Ikuta, A., Yasuda, K., & Kanzaki, H. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.12.7023 · Cited by 114 · see citing works
“If fertilization occurs, high circulating P levels are important not only for facilitating implantation, but also for maintaining pregnancy by stimulating uterine growth ( 1 , 2). Decidualization is a dramatic morphological and functional differentiation of the human endometrium during the Pdominant secretory phase of…”
BackgroundReview of the literature on combined oral contraceptives and cancer
Kamani, M. O., Akgör, U., & Gültekin, M. (2022) · ecancermedicalscience · doi:10.3332/ecancer.2022.1416 · Cited by 114 · see citing works
Zhang, X., Zhang, D., Michel, F. J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212098200 · Cited by 109 · see citing works
Kurita, T., Lee, K.-J., Saunders, P. T. K., Cooke, P. S., Taylor, J. A., Lubahn, D. B., Zhao, C., Mäkelä, S., Gustafsson, J., Dahiya, R., et al. (2001) · Biology of Reproduction · doi:10.1095/biolreprod64.1.272 · Cited by 106 · see citing works
Chen, B., Pan, H., Zhu, L., Deng, Y., & Pollard, J. W. (2005) · Molecular Endocrinology · doi:10.1210/me.2004-0274 · Cited by 104 · see citing works
“P4, in contrast, down-regulates CDK4 as well as CDK2 activity through an inhibition of cyclin D1 expression and induction of the cell cycle inhibitors p27, p21 and Ink4c (p18) activity that act in concert to inhibit these CDKs (43, 44, 48).”
InfluentialProgesterone metabolites in breast cancer
Wiebe, J. P. (2006) · Endocrine Related Cancer · doi:10.1677/erc.1.01010 · Cited by 103 · see citing works
Said, T. K., Conneely, O. M., Medina, D., O’Malley, B. W., & Lydon, J. P. (1997) · Endocrinology · doi:10.1210/endo.138.9.5436 · Cited by 106 · see citing works
Endometrial Cancer: Hormonal Factors, the Perimenopausal "Window of Risk," and Isoflavones
Hale, G. E., Hughes, C. L., & Cline, J. M. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.1.8132 · Cited by 114 · see citing works
“In addition, insulin has been observed to decrease PR-progesterone binding (138) and attenuate the antiproliferative actions of antiestrogens (79) (Table 1).”
BackgroundModulation of AP-1 activity by the human progesterone receptor in endometrial adenocarcinoma cells.
Bamberger, A., Bamberger, C. M., Gellersen, B., & Schulte, H. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.12.6169 · Cited by 97 · see citing works
Simmen, R. C. M., Eason, R. R., McQuown, J. R., Linz, A. L., Kang, T. J., Chatman, L., Till, S. R., Fujii‐Kuriyama, Y., Simmen, F. A., & Oh, S. P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403139200 · Cited by 97 · see citing works
Molecular Cloning and Functional Characterization of a Zebrafish Nuclear Progesterone Receptor1
Chen, S. X., Bogerd, J., García-López, Á., de Jonge, H., de Waal, P. P., Hong, W., & Schulz, R. W. (2009) · Biology of Reproduction · doi:10.1095/biolreprod.109.077644 · Cited by 97 · see citing works
“In mammals, progesterone signaling regulates multiple reproductive processes in females, including follicle growth, oocyte maturation, ovulation, implantation, and the maintenance of pregnancy [1].”
Background
- 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 › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › 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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