Cited by 660Estrogen and related hormone effectsProstate Cancer Treatment and ResearchGrowth Hormone and Insulin-like Growth Factors

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Progestin regulation of cellular proliferation.

CLARKE, CHRISTINE L., SUTHERLAND, ROBERT L.·1990·Endocrine Reviews

DOI 10.1210/edrv-11-2-266

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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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Background
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Johnson, M. L., Redmer, D. A., & Reynolds, L. P. (1997) · Biology of Reproduction · doi:10.1095/biolreprod57.3.588 · Cited by 61
Oocyte selection of mutations affecting cytoplasmic polyadenylation of maternal mRNAs
Verrotti, A. C., & Strickland, S. (1997) · Molecular Reproduction and Development · doi:10.1002/(sici)1098-2795(199704)46:4 · Cited by 10
Progestin Regulation of Estrogen Receptor Messenger RNA in Human Breast Cancer Cells
Alexander, I. E., Shine, J., & Sutherland, R. L. (1990) · Molecular Endocrinology · doi:10.1210/mend-4-6-821 · Cited by 60
Self-citation
Cell Cycle Machinery:
Butt, A. J., Caldon, C. E., McNeil, C. M., Swarbrick, A., Musgrove, E. A., & Sutherland, R. L. (2008) · Advances in Experimental Medicine and Biology · doi:10.1007/978-0-387-78818-0_12 · Cited by 59
Self-citation
Progestins inhibit the growth of MDA-MB-231 cells transfected with progesterone receptor complementary DNA.
Lin, V. C. L., Ng, E. H., Aw, S. E., et al. (1999) · PubMed · Cited by 59
Progesterone receptor isoforms A and B in human epithelial ovarian carcinoma: immunohistochemical and RT-PCR studies
Akahira, J., Inoue, T., Suzuki, T., Ito, K., Konno, R., Sato, S., Moriya, T., Okamura, K., Yajima, A., & Sasano, H. (2000) · British Journal of Cancer · doi:10.1054/bjoc.2000.1463 · Cited by 59
“The biological role of progesterone in epithelial ovarian carcinoma is unknown, but progesterone is, in general, considered to function antagonistically to oestrogen-mediated cell proliferation (Clarke and Sutherland, 1990).”
Background
Progesterone receptor regulation by retinoic acid in the human breast cancer cell line T-47D.
Clarke, C. L., Roman, S. D., Graham, J. D., Koga, M., & Sutherland, R. L. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)38400-5 · Cited by 59
Self-citation
Postmenopausal hormone therapy and breast cancer
Speroff, L. (1996) · Obstetrics and Gynecology · doi:10.1016/0029-7844(95)00428-9 · Cited by 57
Progestins Induce Down-Regulation of Insulin-Like Growth Factor-I (IGF-I) Receptors in Human Breast Cancer Cells: Potential Autocrine Role of IGF-II
Papa, V., Hartmann, K. K. P., Rosenthal, S. M., Maddux, B. A., Siiteri, P. K., & Goldfine, I. D. (1991) · Molecular Endocrinology · doi:10.1210/mend-5-5-709 · Cited by 59
“Progestins have a variety of metabolic and proliferative effects on breast cancer cells (16,17).”
Background
Identification of PRG1, A Novel Progestin-Responsive Gene with Sequence Homology to 6-Phosphofructo-2-Kinase/Fructose- 2,6-Bisphosphatase
Hamilton, J. A., Callaghan, M. J., Sutherland, R. L., et al. (1997) · Molecular Endocrinology · doi:10.1210/mend.11.4.9909 · Cited by 58
Self-citation
Coexistence of Intracellular and Membrane-Bound Progesterone Receptors in Human Testis
Shah, C., Modi, D. N., Sachdeva, G., Gadkar, S., & Puri, C. P. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0793 · Cited by 58
Prevention of bone loss by EM-800 and raloxifene in the ovariectomized rat
Martel, C., Picard, S., Richard, V., Bélanger, A., Labrie, C., & Labrie, F. (2000) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(00)00087-x · Cited by 57
“It should be mentioned that recent data suggest that not only estrogens but also progestins can have a negative impact on breast cancer [8,9,40,41].”
Background
Estrogenic actions of RU486 in hormone-responsive MCF-7 human breast cancer cells.
Jeng, M. H., Langan-Fahey, S. M., & Jordan, V. C. (1993) · Endocrinology · doi:10.1210/endo.132.6.8504763 · Cited by 57
Regulation of the expression and activity by progestins of a member of the SOX gene family of transcriptional modulators
Graham, J., Sm, H., Tran, N. T., et al. (1999) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0220295 · Cited by 56
“The general chemicals used were of molecular biological or analytical reagent grade, as required by specific methodology, and were from the same sources as previously listed (Clarke et al. 1990).”
MethodSelf-citation
Cell-specific immuno-localization of progesterone receptor alpha in the rabbit ovary during pregnancy and after parturition
Abd‐Elkareem, M. (2017) · Animal Reproduction Science · doi:10.1016/j.anireprosci.2017.03.007 · Cited by 56
“These include ovulation, growth and differentiation of ovarian structures, uterine and mammary gland development, pregnancy establishment and maintenance and the neuro-behavioral expression associated with sexual responsiveness (Clarke and Sutherland, 1990; Lydon et al., 1995; Pinter et al., 1996; Conneely et al., 200…”
Background
Cyclin D1 Overexpression Induces Progestin Resistance in T-47D Breast Cancer Cells Despite p27Kip1 Association with Cyclin E-Cdk2
Musgrove, E. A., Hunter, L.-J. K., Lee, C. S. L., Swarbrick, A., Hui, R., & Sutherland, R. L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106371200 · Cited by 55
Self-citation
Nuclear Hormone Receptors
Zaveri, N. T., & Murphy, B. J. (2007) · Elsevier eBooks · doi:10.1016/b0-08-045044-x/00063-8 · Cited by 59
Distribution of estrogen and progesterone receptors isoforms in endometrial cancer
Kreizman-Shefer, H., Pricop, J., Goldman, S., et al. (2014) · Diagnostic Pathology · doi:10.1186/1746-1596-9-77 · Cited by 55
“The physiological roles of progesterone in the regulation of endometrial tissue are, in general, considered to antagonize estrogen-mediated cell proliferation and to induce cellular differentiation [14,15].”
Background
Oestrogen and progesterone receptors in feline fibroadenomatous change: an immunohistochemical study
Mulas, J. M. D. L., Millán, Y., Bautista, M. J., et al. (2000) · Research in Veterinary Science · doi:10.1053/rvsc.1999.0327 · Cited by 55
Immunolocalization of liver receptor homologue-1 (LRH-1) in human breast carcinoma: Possible regulator of in situ steroidogenesis
Miki, Y., Clyne, C. D., Suzuki, T., Moriya, T., Shibuya, R., Nakamura, Y., Ishida, T., Yabuki, N., Kitada, K., Hayashi, S., et al. (2006) · Cancer Letters · doi:10.1016/j.canlet.2005.11.038 · Cited by 55
“It is well-known that progesterone inhibits cellular proliferation through PR [41], and administration of progestins is currently performed as an endocrine therapy in breast carcinoma patients [3], although some controversies exist with respect to progesterone actions in breast carcinoma [41,42].”
Background
The Antagonists RU486 and ZK98299 Stimulate Progesterone Receptor Binding to Deoxyribonucleic Acid in Vitro and in Vivo, but Have Distinct Effects on Receptor Conformation*
Gass, E. K., Leonhardt, S. A., Nordeen, S. K., et al. (1998) · Endocrinology · doi:10.1210/endo.139.4.5944 · Cited by 55
“Additionally, progesterone is implicated in the development and progression of breast and uterine malignancies (1, 2).”
Background
Roles of Estrogen and Progesterone in Normal Mammary Gland Development
Shyamala, G. (1997) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(96)00207-x · Cited by 58
Immunocytochemical Localization of Sex Steroid Hormone Receptors in Normal Human Mammary Gland
Li, S., Han, B., Liu, G., Li, S., Ouellet, J., Labrie, F., & Pelletier, G. (2009) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.2009.954644 · Cited by 56
“The twoPR receptors are transcribed from the samegene, throughalternative promoter usage (Clarke and Sutherland 1990).”
Background
Progesterone receptor is not required for progesterone action in the rat corpus luteum of pregnancy☆
Telleria, C. M., Stocco, C. O., Stati, A. O., & Deis, R. P. (1999) · Steroids · doi:10.1016/s0039-128x(99)00061-6 · Cited by 55
New insights into estrogen receptor function in human breast cancer
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A comparison of the action of progestins and estrogen on the growth and differentiation of normal adult human osteoblast-like cells in vitro
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Role of Epigenomics in Ovarian and Endometrial Cancers
Balch, C., Matei, D. E., Huang, T. H. ‐., & Nephew, K. P. (2010) · Epigenomics · doi:10.2217/epi.10.19 · Cited by 52
Induction of Overt Menstruation in Intact Mice
Rudolph, M., Döcke, W., Müller, A., Menning, A., Röse, L., Zollner, T. M., & Gashaw, I. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032922 · Cited by 52
“The growth activity of stroma cells is elevated in both the proliferative phase and the late secretory phase of the menstrual cycle, whereby the latter is induced by progesterone in a second wave of proliferation [21,22].”
Background
A complex role for the progesterone receptor in the response to vascular injury
Karas, R. H., van Eickels, M., Lydon, J. P., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200111374 · Cited by 53

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
DOI: 10.1210/edrv-11-2-266
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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Progestin regulation of cellular proliferation.

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