Subscribe to RSS
DOI: 10.1055/s-2007-973432
Non-Genomic Actions of Progesterone in the Normal and Neoplastic Mammalian Ovary
Publication History
Publication Date:
20 April 2007 (online)
ABSTRACT
This review summarizes recent findings on the non-genomic or membrane-initiated actions of progesterone that regulate the function of the normal and neoplastic mammalian ovary. This review focuses on three receptors: the classic progesterone receptor, the membrane progesterone receptors (MPRα, β, and γ) that were initially cloned from seatrout ovaries, and a progesterone binding protein referred to as progesterone receptor membrane component-1 (PGRMC1). Specifically, the structure of each of these receptors is compared and related to their capacity to activate various signal transduction pathways. Then the biological effects of P4 on the function of granulosa cells, luteal cells, ovarian surface epithelial cells, and ovarian cancers that are derived from the ovarian surface epithelial cells are discussed in relationship to the expression of each of these receptors. Whenever possible, studies involving human cells and tissues are presented, although data from other mammalian species are used to supplement the human studies to provide a more complete picture of this complex and rapidly developing area of membrane-initiated actions of progesterone.
KEYWORDS
Progesterone - granulosa cells - luteal cells - ovarian surface epithelial cells - ovarian cancer
REFERENCES
- 1 Bramley T. Non-genomic progesterone receptors in the mammalian ovary: some unresolved issues. Reproduction. 2003; 125 3-15
- 2 Stouffer R L. Progesterone as a mediator of gonadotrophin action in the corpus luteum: beyond steroidogenesis. Hum Reprod Update. 2003; 9 99-117
- 3 Ho S M. Estrogen, progesterone and epithelial ovarian cancer. Reprod Biol Endocrinol. 2003; 1 73-80
- 4 Syed V, Ho S M. Progesterone-induced apoptosis in immortalized normal and malignant human ovarian surface epithelial cells involves enhanced expression of FasL. Oncogene. 2003; 22 6883-6890
- 5 Peluso J J. Progesterone as a regulator of granulosa cell viability. J Steroid Biochem Mol Biol. 2003; 85 167-173
- 6 Natraj U, Richards J S. Hormonal regulation, localization, and functional activity of the progesterone receptor in granulosa cells of rat preovulatory follicles. Endocrinology. 1993; 133 761-769
- 7 Park O K, Mayo K E. Transient expression of progesterone receptor messenger RNA in ovarian granulosa cells after the preovulatory luteinizing hormone surge. Mol Endocrinol. 1991; 5 967-978
- 8 Li X, Lonard D M, O'Malley B W. A contemporary understanding of progesterone receptor function. Mech Ageing Dev. 2004; 125 669-678
- 9 Younglai E V, Wu Y J, Kwan T K, Kwan C Y. Non-genomic action of estradiol and progesterone on cytosolic calcium concentrations in primary cultures of human granulosa-lutein cells. Hum Reprod. 2005; 20 2383-2390
- 10 Peluso J J, Fernandez G, Pappalardo A, White B A. Membrane-initiated events account for progesterone's ability to regulate intracellular free calcium levels and inhibit rat granulosa cell mitosis. Biol Reprod. 2002; 67 379-385
- 11 Peluso J J, Fernandez G, Pappalardo A, White B A. Characterization of a putative membrane receptor for progesterone in rat granulosa cells. Biol Reprod. 2001; 65 94-101
- 12 Belelli D, Lambert J J. Neurosteroids: endogenous regulators of the GABA(A) receptor. Nat Rev Neurosci. 2005; 6 565-575
- 13 Akinci M K, Schofield P R. Widespread expression of GABA(A) receptor subunits in peripheral tissues. Neurosci Res. 1999; 35 145-153
- 14 Falkenstein E, Eisen C, Schmieding K et al.. Chemical modification and structural analysis of the progesterone membrane binding protein from porcine liver membranes. Mol Cell Biochem. 2001; 218 71-79
- 15 Martinez S, Grandy R, Pasten P et al.. Plasma membrane destination of the classical Xenopus laevis progesterone receptor accelerates progesterone-induced oocyte maturation. J Cell Biochem. 2006; 99 853-859
- 16 Morrill G A, Erlichman J, Gutierrez-Juarez R, Kostellow A B. The steroid-binding subunit of the Na/K-ATPase as a progesterone receptor on the amphibian oocyte plasma membrane. Steroids. 2005; 70 933-945
- 17 Saner K J, Welter B H, Zhang F et al.. Cloning and expression of a novel, truncated, progesterone receptor. Mol Cell Endocrinol. 2003; 200 155-163
- 18 Welter B H, Hansen E L, Saner K J, Wei Y, Price T M. Membrane-bound progesterone receptor expression in human aortic endothelial cells. J Histochem Cytochem. 2003; 51 1049-1055
- 19 Zhu Y, Bond J, Thomas P. Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor. Proc Natl Acad Sci USA. 2003; 100 2237-2242
- 20 Zhu Y, Rice C D, Pang Y, Pace M, Thomas P. Cloning, expression, and characterization of a membrane progestin receptor and evidence it is an intermediary in meiotic maturation of fish oocytes. Proc Natl Acad Sci USA. 2003; 100 2231-2236
- 21 Brenner R M, Slayden O D. Progesterone receptor antagonists and the endometrial antiproliferative effect. Semin Reprod Med. 2005; 23 74-81
- 22 Chabbert-Buffet N, Meduri G, Bouchard P, Spitz I M. Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications. Hum Reprod Update. 2005; 11 293-307
- 23 Cui X, Schiff R, Arpino G, Osborne C K, Lee A V. Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol. 2005; 23 7721-7735
- 24 Katiyar P, Ma Y, Fan S, Pestell R G, Furth P A, Rosen E M. Regulation of progesterone receptor signaling by BRCA1 in mammary cancer. Nucl Recept Signal. 2006; 4 e006-e009
- 25 Osborne C K, Schiff R, Arpino G, Lee A S, Hilsenbeck V G. Endocrine responsiveness: understanding how progesterone receptor can be used to select endocrine therapy. Breast. 2005; 14 458-465
- 26 Spitz I M. Progesterone receptor antagonists and selective progesterone receptor modulators (SPRMs). Semin Reprod Med. 2005; 23 3-7
- 27 Leonhardt S A, Boonyaratanakornkit V, Edwards D P. Progesterone receptor transcription and non-transcription signaling mechanisms. Steroids. 2003; 68 761-770
- 28 Losel R, Breiter S, Seyfert M, Wehling M, Falkenstein E. Classic and non-classic progesterone receptors are both expressed in human spermatozoa. Horm Metab Res. 2005; 37 10-14
- 29 Mifsud W, Bateman A. Membrane-bound progesterone receptors contain a cytochrome b5-like ligand-binding domain. Genome Biol. 2002; 3 RESEARCH0068-e072
- 30 Crudden G, Chitti R E, Craven R J. Hpr6 (heme-1 domain protein) regulates the susceptibility of cancer cells to chemotherapeutic drugs. J Pharmacol Exp Ther. 2006; 316 448-455
- 31 Peluso J J, Pappalardo A, Losel R, Wehling M. Progesterone membrane receptor component 1 expression in the immature rat ovary and its role in mediating progesterone's antiapoptotic action. Endocrinology. 2006; 147 3133-3140
- 32 Peluso J J, Pappalardo A, Losel R, Wehling M. Expression and function of PAIRBP1 within gonadotropin-primed immature rat ovaries: PAIRBP1 regulation of granulosa and luteal cell viability. Biol Reprod. 2005; 73 261-270
- 33 Peluso J J. Multiplicity of progesterone's actions and receptors in the mammalian ovary. Biol Reprod. 2006; 75 2-8
- 34 Peluso J J, Pappalardo A, Fernandez G, Wu C A. Involvement of an unnamed protein, RDA288, in the mechanism through which progesterone mediates its antiapoptotic action in spontaneously immortalized granulosa cells. Endocrinology. 2004; 145 3014-3022
- 35 Winneker R C, Fensome A, Wrobel J E, Zhang Z, Zhang P. Nonsteroidal progesterone receptor modulators: structure activity relationships. Semin Reprod Med. 2005; 23 46-57
- 36 Boonyaratanakornkit V, Edwards D P. Receptor mechanisms of rapid extranuclear signalling initiated by steroid hormones. Essays Biochem. 2004; 40 105-120
- 37 Lange C A. Making sense of cross-talk between steroid hormone receptors and intracellular signaling pathways: who will have the last word?. Mol Endocrinol. 2004; 18 269-278
- 38 Karteris E, Zervou S, Pang Y et al.. Progesterone signaling in human myometrium through two novel membrane G protein-coupled receptors: potential role in functional progesterone withdrawal at term. Mol Endocrinol. 2006; 20 1519-1534
- 39 Peluso J J, Pappalardo A. Progesterone regulates granulosa cell viability through a protein kinase G-dependent mechanism that may involve 14-3-3sigma. Biol Reprod. 2004; 71 1870-1878
- 40 Peluso J J, Bremner T, Fernandez G, Pappalardo A, White B A. Expression pattern and role of a 60-kilodalton progesterone binding protein in regulating granulosa cell apoptosis: involvement of the mitogen-activated protein kinase cascade. Biol Reprod. 2003; 68 122-128
- 41 Nilsson E E, Stanfield J, Skinner M K. Interactions between progesterone and tumor necrosis factor-alpha in the regulation of primordial follicle assembly. Reproduction. 2006; 132 877-886
- 42 Braw-Tal R. The initiation of follicle growth: the oocyte or the somatic cells?. Mol Cell Endocrinol. 2002; 187 11-18
- 43 Taymor M L. The regulation of follicle growth: some clinical implications in reproductive endocrinology. Fertil Steril. 1996; 65 235-247
- 44 Vitt U A, Hsueh A J. Stage-dependent role of growth differentiation factor-9 in ovarian follicle development. Mol Cell Endocrinol. 2001; 183 171-177
- 45 Chaffkin L M, Luciano A A, Peluso J J. The role of progesterone in regulating human granulosa cell proliferation and differentiation in vitro. J Clin Endocrinol Metab. 1993; 76 696-700
- 46 Lederer K J, Luciano A M, Pappalardo A, Peluso J J. Proliferative and steroidogenic capabilities of rat granulosa cells of different sizes. J Reprod Fertil. 1995; 103 47-54
- 47 Luciano A M, Peluso J J. Effect of in vivo gonadotropin treatment on the ability of progesterone, estrogen, and cyclic adenosine 5′-monophosphate to inhibit insulin-dependent granulosa cell mitosis in vitro. Biol Reprod. 1995; 53 664-669
- 48 Luciano A M, Pappalardo A, Ray C, Peluso J J. Epidermal growth factor inhibits large granulosa cell apoptosis by stimulating progesterone synthesis and regulating the distribution of intracellular free calcium. Biol Reprod. 1994; 51 646-654
- 49 Shao R, Markstrom E, Friberg P A, Johansson M, Billig H. Expression of progesterone receptor (PR) A and B isoforms in mouse granulosa cells: stage-dependent PR-mediated regulation of apoptosis and cell proliferation. Biol Reprod. 2003; 68 914-921
- 50 Agarwal P, Peluso J J, White B A. Steroidogenic factor-1 expression is transiently repressed and c-myc expression and deoxyribonucleic acid synthesis are induced in rat granulosa cells during the periovulatory period. Biol Reprod. 1996; 55 1271-1275
- 51 Piontkewitz Y, Sundfeldt K, Hedin L. The expression of c-myc during follicular growth and luteal formation in the rat ovary in vivo. J Endocrinol. 1997; 152 395-406
- 52 Shao R, Rung E, Weijdegard B, Billig H. Induction of apoptosis increases SUMO-1 protein expression and conjugation in mouse periovulatory granulosa cells in vitro. Mol Reprod Dev. 2006; 73 50-60
- 53 Rung E, Friberg P A, Shao R et al.. Progesterone-receptor antagonists and statins decrease de novo cholesterol synthesis and increase apoptosis in rat and human periovulatory granulosa cells in vitro. Biol Reprod. 2005; 72 538-545
- 54 Svensson E C, Markstrom E, Shao R, Andersson M, Billig H. Progesterone receptor antagonists Org 31710 and RU 486 increase apoptosis in human periovulatory granulosa cells. Fertil Steril. 2001; 76 1225-1231
- 55 Svensson E C, Markstrom E, Andersson M, Billig H. Progesterone receptor-mediated inhibition of apoptosis in granulosa cells isolated from rats treated with human chorionic gonadotropin. Biol Reprod. 2000; 63 1457-1464
- 56 Hubbard C J, Greenwald G S. Cyclic nucleotides, DNA, and steroid levels in ovarian follicles and corpora lutea of the cyclic hamster. Biol Reprod. 1982; 26 230-240
- 57 Amsterdam A, Keren-Tal I, Aharoni D et al.. Steroidogenesis and apoptosis in the mammalian ovary. Steroids. 2003; 68 861-867
- 58 Rothchild I. The corpus luteum revisited: are the paradoxical effects of RU486 a clue to how progesterone stimulates its own secretion?. Biol Reprod. 1996; 55 1-4
- 59 Robker R L, Russell D L, Espey L L, Lydon J P, O'Malley B W, Richards J S. Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases. Proc Natl Acad Sci USA. 2000; 97 4689-4694
- 60 Suchanek M, Radzikowska A, Thiele C. Photo-leucine and photo-methionine allow identification of protein-protein interactions in living cells. Nat Methods. 2005; 2 261-267
- 61 Yang T, Espenshade P J, Wright M E et al.. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell. 2002; 110 489-500
- 62 Christenson L K, Osborne T F, McAllister J M, Strauss III J F. Conditional response of the human steroidogenic acute regulatory protein gene promoter to sterol regulatory element binding protein-1a. Endocrinology. 2001; 142 28-36
- 63 Christenson L K, Strauss III J F. Steroidogenic acute regulatory protein: an update on its regulation and mechanism of action. Arch Med Res. 2001; 32 576-586
- 64 Min L, Takemori H, Nonaka Y et al.. Characterization of the adrenal-specific antigen IZA (inner zone antigen) and its role in the steroidogenesis. Mol Cell Endocrinol. 2004; 215 143-148
- 65 Makino A, Ozaki Y, Matsubara H et al.. Role of apoptosis controlled by cytochrome c released from mitochondria for luteal function in human granulosa cells. Am J Reprod Immunol. 2005; 53 144-152
- 66 Makrigiannakis A, Coukos G, Christofidou-Solomidou M, Montas S, Coutifaris C. Progesterone is an autocrine/paracrine regulator of human granulosa cell survival in vitro. Ann NY Acad Sci. 2000; 900 16-25
- 67 Engmann L, Losel R, Wehling M, Peluso J J. Progesterone regulation of human granulosa/luteal cell viability by an RU486-independent mechanism. J Clin Endocrinol Metab. 2006; 91 4962-4968
- 68 Cai Z, Stocco C. Expression and regulation of progestin membrane receptors in the rat corpus luteum. Endocrinology. 2005; 146 5522-5532
- 69 Modan B, Ron E, Lerner-Geva L et al.. Cancer incidence in a cohort of infertile women. Am J Epidemiol. 1998; 147 1038-1042
-
70 Yen S.
Endocrinology of pregnancy . In: Cresy R, Rensik R Maternal-Fetal Medicine: Principles and Practice. Philadelphia, PA; Saunders 1994: 382-412 - 71 Krebs C J, Jarvis E D, Chan J, Lydon J P, Ogawa S, Pfaff D W. A membrane-associated progesterone-binding protein, 25-Dx, is regulated by progesterone in brain regions involved in female reproductive behaviors. Proc Natl Acad Sci USA. 2000; 97 12816-12821
John J PelusoPh.D.
Department of Cell Biology (MC3505), University of Connecticut School of Medicine
263 Farmington Avenue, Farmington, CT 06030
Email: peluso@nso2.uchc.edu