Therapeutic effects of progesterone and its metabolites in traumatic brain injury may involve non-classical signaling mechanisms

Frontiers in Neuroscience

Volumn , Issue 7 JUN, 2013, Pages

  Cooke, Paul S ^a   Nanjappa, Manjunatha K ^a   Yang, Zhihui ^b   Wang, Kevin K W ^a,b  

^a University of Florida College of Veterinary Medicine   (United States)

^b UNIVERSITY OF FLORIDA   (United States)

Author keywords

Allopregnanolone; Controlled cortical impact; Membrane receptors; Progesterone receptor; Progesterone receptor membrane component 1

Indexed keywords

3ALPHA HYDROXY 5ALPHA PREGNAN 20 ONE; 4 AMINOBUTYRIC ACID A RECEPTOR; 5ALPHA PREGNANE 3,20 DIONE; DRUG METABOLITE; MITOCHONDRIAL PERMEABILITY TRANSITION PORE; PREGNANE X RECEPTOR; PROGESTERONE; PROGESTERONE RECEPTOR;

CLINICAL TRIAL (TOPIC); DRUG EFFECT; DRUG MECHANISM; HORMONE SYNTHESIS; HUMAN; NEUROPROTECTION; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); SHORT SURVEY; SIGNAL TRANSDUCTION; THERAPY EFFECT; TRAUMATIC BRAIN INJURY;

EID: 84884403851     PISSN: 16624548     EISSN: 1662453X     Source Type: Journal    
DOI: 10.3389/fnins.2013.00108     Document Type: Short Survey

References (90)

1. Agís-Balboa, R. C., Pinna, G., Zhubi, A., Maloku, E., Veldic, M., Costa, E., et al. (2006). Characterization of brain neurons that express enzymes mediating neurosteroid biosynthesis. Proc. Natl. Acad. Sci. U.S.A. 103, 14602-14607. doi: 10.1073/pnas.0606544103
2. Anderson, G. D., Farin, F. M., Bammler, T. K., Beyer, R. P., Swan, A. A., Wilkerson, H. W., et al. (2011). The effect of progesterone dose on gene expression after traumatic brain injury. J. Neurotrauma 28, 1827-1843. doi: 10.1089/neu.2011.1911
3. Ardeshiri, A., Kelley, M. H., Korner, I. P., Hurn, P. D., and Herson, P. S. (2006). Mechanism of progesterone neuroprotection of rat cerebellar Purkinje cells following oxygen-glucose deprivation. Eur. J. Neurosci. 24, 2567-2574. doi: 10.1111/j.1460-9568.2006.05142.x
4. Baulieu, E. E. (1981). "Steroid hormones in the brain: several mechanisms," in Steroid Hormone Regulation of the Brain, eds K. Fuxe, J. A. Gustafson, and L. Wettenberg (Elmsford, NY: Pergamon), 3-14.
5. Baulieu, E. E., Robel, P., and Schumacher, M. (2001). Neurosteroids: beginning of the story. Int. Rev. Neurobiol. 46, 1-32. doi: 10.1016/S0074-7742(01)46057-0
6. Baykara, B., Aksu, I., Buyuk, E., Kiray, M., Sisman, A., Baykara, B., et al. (2013). Progesterone treatment decreases traumatic brain injury induced anxiety and is correlated with increased serum IGF-1 levels; prefrontal cortex, amygdala, hippocampus neuron density; and reduced serum corticosterone levels in immature rats. Biotech. Histochem. doi: 10.3109/10520295.2013.769630. [Epub ahead of print].
7. Brinton, R. D., Thompson, R. F., Foy, M. R., Baudry, M., Wang, J., Finch, C. E., et al. (2008). Progesterone receptors: form and function in brain. Front. Neuroendocrinol. 29, 313-339. doi: 10.1016/j.yfrne.2008.02.001
8. Cahill, M. A. (2007). Progesterone receptor membrane component 1: an integrative review. J. Steroid Biochem. Mol. Biol. 105, 16-36. doi: 10.1016/j.jsbmb.2007.02.002
9. Champion, H. R., Holcomb, J. B., and Young, L. A. (2009). Injuries from explosions. J. Trauma 66, 1468-1476. doi: 10.1097/TA.0b013e3181a27e7f
10. Chan, G. N., Hoque, M. T., Cummins, C. L., and Bendayan, R. (2011). Regulation of P-glycoprotein by orphan nuclear receptors in human brain microvessel endothelial cells. J. Neurochem. 118, 163-175. doi: 10.1111/j.1471-4159.2011.07288.x
11. Chen, G., Shi, J. X., Qi, M., Wang, H. X., and Hang, C. H. (2008). Effects of progesterone on intestinal inflammatory response, mucosa structure alterations, and apoptosis following traumatic brain injury in male rats. J. Surg. Res. 147, 92-98. doi: 10.1016/j.jss.2007.05.029
12. Ciriza, I., Carrero, P., Frye, C. A., and Garcia-Segura, L. M. (2006). Reduced metabolites mediate neuroprotective effects of progesterone in the adult rat hippocampus. The synthetic progestin medroxyprogesterone acetate (Provera) is not neuroprotective. J. Neurobiol. 66, 916-928. doi: 10.1002/neu.20293
13. Conneely, O. M., Mulac-Jericevic, B., Lydon, J. P., and De Mayo, F. J. (2001). Reproductive functions of the progesterone receptor isoforms: lessons from knock-out mice. Mol. Cell. Endocrinol. 179, 97-103. doi: 10.1016/S0303-7207(01)00465-8
14. Crompton, M. (1999). The mitochondrial permeability transition pore and its role in cell death. Biochem. J. 341, 233-249. doi: 10.1042/0264-6021:3410233
15. Cutler, S. M., Cekic, M., Miller, D. M., Wali, B., VanLandingham, J. W., and Stein, D. G. (2007). Progesterone improves acute recovery after traumatic brain injury in the aged rat. J. Neurotrauma 24, 1475-1486. doi: 10.1089/neu.2007.0294
16. Cutler, S. M., VanLandingham, J. W., Murphy, A. Z., and Stein, D. G. (2006). Slow-release and injected progesterone treatments enhance acute recovery after traumatic brain injury. Pharmacol. Biochem. Behav. 84, 420-428. doi: 10.1016/j.pbb.2006.05.029
17. Djebaili, M., Guo, Q., Pettus, E. H., Hoffman, S. W., and Stein, D. G. (2005). The neurosteroids progesterone and allopregnanolone reduce cell death, gliosis, and functional deficits after traumatic brain injury in rats. J. Neurotrauma 22, 106-118. doi: 10.1089/neu.2005.22.106
18. Djebaili, M., Hoffman, S. W., and Stein, D. G. (2004). Allopregnanolone and progesterone decrease cell death and cognitive deficits after a contusion of the rat pre-frontal cortex. Neuroscience 123, 349-359. doi: 10.1016/j.neuroscience.2003.09.023
19. Dressing, G. E., Alyea, R., Pang, Y., and Thomas, P. (2012). Membrane progesterone receptors (mPRs) mediate progestin induced antimorbidity in breast cancer cells and are expressed in human breast tumors. Horm. Cancer 3, 101-112. doi: 10.1007/s12672-012-0106-x
20. Dressing, G. E., Pang, Y., Dong, J., and Thomas, P. (2010). Progestin signaling through mPRa in Atlantic croaker granulosa/theca cell cocultures and its involvement in progestin inhibition of apoptosis. Endocrinology 151, 5916-5926. doi: 10.1210/en.2010-0165
21. Espinoza, T. R., and Wright, D. W. (2011). The role of progesterone in traumatic brain injury. J. Head Trauma Rehabil. 26, 497-499. doi: 10.1097/HTR.0b013e31823088fa
22. Falkenstein, E., Heck, M., Gerdes, D., Grube, D., Christ, M., Weigel, M., et al. (1999). Specific progesterone binding to a membrane protein and related nongenomic effects on Ca2+-fluxes in sperm. Endocrinology 140, 5999-6002. doi: 10.1210/en.140.12.5999
23. Falkenstein, E., Meyer, C., Eisen, C., Scriba, P. C., and Wehling, M. (1996). Full-length cDNA sequence of a progesterone membrane-binding protein from porcine vascular smooth muscle cells. Biochem. Biophys. Res. Commun. 229, 86-89. doi: 10.1006/bbrc.1996.1761
24. Faul, M., Xu, L., Wald, M. M., and Coronado, V. G. (2010). Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations, and Deaths. Atlanta, GA: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. Available online at: http://www.cdc.gov/traumaticbraininjury/pdf/blue_book.pdf
25. Gonzalez, S. L., Labombarda, F., Deniselle, M. C., Mougel, A., Guennoun, R., Schumacher, M., et al. (2005). Progesterone neuroprotection in spinal cord trauma involves up-regulation of brain-derived neurotrophic factor in motoneurons. J. Steroid Biochem. Mol. Biol. 94, 143-149. doi: 10.1016/j.jsbmb.2005.01.016
26. Goss, C. W., Hoffman, S. W., and Stein, D. G. (2003). Behavioral effects and anatomic correlates after brain injury: a progesterone dose-response study. Pharmacol. Biochem. Behav. 76, 231-242. doi: 10.1016/j.pbb.2003.07.003
27. Guennoun, R., Meffre, D., Labombarda, F., Gonzalez, S. L., Deniselle, M. C., Stein, D. G., et al. (2008). The membrane-associated progesterone-binding protein 25-Dx: expression, cellular localization and up-regulation after brain and spinal cord injuries. Brain Res. Rev. 57, 493-505. doi: 10.1016/j.brainresrev.2007.05.009
28. He, J., Evans, C. O., Hoffman, S. W., Oyesiku, N. M., and Stein, D. G. (2004a). Progesterone and allopregnanolone reduce inflammatory cytokines after traumatic brain injury. Exp. Neurol. 189, 404-412. doi: 10.1016/j.expneurol.2004.06.008
29. He, J., Hoffman, S. W., and Stein, D. G. (2004b). Allopregnanolone, a progesterone metabolite, enhances behavioral recovery and decreases neuronal loss after traumatic brain injury. Restor. Neurol. Neurosci. 22, 19-31.
30. Intlekofer, K. A., and Petersen, S. L. (2011). Distribution of mRNAs encoding classical progestin receptor, progesterone membrane components 1 and 2, serpine mRNA binding protein 1, and progestin and ADIPOQ receptor family members 7 and 8 in rat forebrain. Neuroscience 172, 55-65. doi: 10.1016/j.neuroscience.2010.10.051
31. Ishrat, T., Sayeed, I., Atif, F., Hua, F., and Stein, D. G. (2010). Progesterone and allopregnanolone attenuate blood-brain barrier dysfunction following permanent focal ischemia by regulating the expression of matrix metalloproteinases. Exp. Neurol. 226, 183-190. doi: 10.1016/j.expneurol.2010.08.023
32. Jeong, J. W., Lee, K. Y., Kwak, I., White, L. D., Hilsenbeck, S. G., Lydon, J. P., et al. (2005). Identification of murine uterine genes regulated in a ligand-dependent manner by the progesterone receptor. Endocrinology 146, 3490-3505. doi: 10.1210/en.2005-0016
33. Jones, N. C., Constantin, D., Prior, M. J., Morris, P. G., Marsden, C. A., and Murphy, S. (2005). The neuroprotective effect of progesterone after traumatic brain injury in male mice is independent of both the inflammatory response and growth factor expression. Eur. J. Neurosci. 21, 1547-1554. doi: 10.1111/j.1460-9568.2005.03995.x
34. Kaasik, A., Safiulina, D., Kalda, A., and Zharkovsky, A. (2003). Dehydroepiandrosterone with other neurosteroids preserve neuronal mitochondria from calcium overload. J. Steroid Biochem. Mol. Biol. 87, 97-103. doi: 10.1016/S0960-0760(03)00389-3
35. Kasturi, B. S., and Stein, D. G. (2009). Progesterone decreases cortical and sub-cortical edema in young and aged ovariectomized rats with brain injury. Restor. Neurol. Neurosci. 27, 265-275. doi: 10.3233/RNN-2009-0475
36. Keller, E. A., Zamparini, A., Borodinsky, L. N., Gravielle, M. C., and Fiszman, M. L. (2004). Role of allopregnanolone on cerebellar granule cells neurogenesis. Brain Res. Dev. Brain Res. 153, 13-17. doi: 10.1016/j.devbrainres.2004.07.009
37. Kelley, M. H., Kuroiwa, M., Taguchi, N., and Herson, P. S. (2011). Sex difference in sensitivity to allopregnanolone neuroprotection in mice correlates with effect on spontaneous inhibitory post synaptic currents. Neuropharmacology 61, 724-729. doi: 10.1016/j.neuropharm.2011.05.017
38. Kelley, M. H., Taguchi, N., Ardeshiri, A., Kuroiwa, M., Hurn, P. D., Traystman, R. J., et al. (2008). Ischemic insult to cerebellar Purkinje cells causes diminished GABAA receptor function and allopregnanolone neuroprotection is associated with GABAA receptor stabilization. J. Neurochem. 107, 668-678. doi: 10.1111/j.1471-4159.2008.05617.x
39. Labombarda, F., Ghoumari, A. M., Liere, P., De Nicola, A. F., Schumacher, M., and Guennoun, R. (2013). Neuroprotection by steroids after neurotrauma in organotypic spinal cord cultures: a key role for progesterone receptors and steroidal modulators of GABAA receptors. Neuropharmacology 71, 46-55. doi: 10.1016/j.neuropharm.2013.03.010
40. Labombarda, F., Gonzalez, S. L., Deniselle, M. C., Vinson, G. P., Schumacher, M., De Nicola, A. F., et al. (2003). Effects of injury and progesterone treatment on progesterone receptor and progesterone binding protein 25-Dx expression in the rat spinal cord. J. Neurochem. 87, 902-913. doi: 10.1046/j.1471-4159.2003.02055.x
41. Lamba, V., Yasuda, K., Lamba, J. K., Assem, M., Davila, J., Strom, S., et al. (2004). PXR NR1I2: splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators. Toxicol. Appl. Pharmacol. 199, 251-265. doi: 10.1016/j.taap.2003.12.027
42. Lambert, J. J., Belelli, D., Harney, S. C., Peters, J. A., and Frenguelli, B. G. (2001). Modulation of native and recombinant GABAA receptors by endogenous and synthetic neuroactive steroids. Brain Res. Brain Res. Rev. 37, 68-80. doi: 10.1016/S0165-0173(01)00124-2
43. Langmade, S. J., Gale, S. E., Frolov, A., Mohri, I., Suzuki, K., Mellon, S. H., et al. (2006). Pregnane X receptor (PXR) activation: a mechanism for neuroprotection in a mouse model of Niemann-Pick C disease. Proc. Natl. Acad. Sci. U.S.A. 103, 13807-13812. doi: 10.1073/pnas.0606218103
44. Liu, A., Margaill, I., Zhang, S., Labombarda, F., Coqueran, B., Delespierre, B., et al. (2012). Progesterone receptors: a key for neuroprotection in experimental stroke. Endocrinology 153, 3747-3757. doi: 10.1210/en.2012-1138
45. Liu, L., Wang, J., Zhao, L., Nilsen, J., McClure, K., Wong, K., et al. (2009). Progesterone increases rat neural progenitor cell cycle gene expression and proliferation via extracellularly regulated kinase and progesterone receptor membrane components 1 and 2. Endocrinology 150, 3186-3196. doi: 10.1210/en.2008-1447
46. Lydon, J. P., DeMayo, F. J., Funk, C. R., Mani, S. K., Hughes, A. R., Montgomery, C. A. Jr, et al. (1995). Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Genes Dev. 9, 2266-2278. doi: 10.1101/gad.9.18.2266
47. Ma, X., Idle, J. R., and Gonzalez, F. J. (2008). The pregnane X receptor: from bench to bedside. Expert Opin. Drug Metab. Toxicol. 4, 895-908. doi: 10.1517/17425255.4.7.895
48. Maas, A. I., Stocchetti, N., and Bullock, R. (2008). Moderate and severe traumatic brain injury in adults. Lancet Neurol. 7, 728-741. doi: 10.1016/S1474-4422(08)70164-9
49. Magnaghi, V., Ballabio, M., Consoli, A., Lambert, J. J., Roglio, I., and Melcangi, R. C. (2006). GABA receptor-mediated effects in the peripheral nervous system: a cross-interaction with neuroactive steroids. J. Mol. Neurosci. 28, 89-102. doi: 10.1385/JMN:28:1:89
50. Meffre, D., Delespierre, B., Gouézou, M., Leclerc, P., Vinson, G. P., Schumacher, M., et al. (2005). The membrane-associated progesterone-binding protein 25-Dx is expressed in brain regions involved in water homeostasis and is up-regulated after traumatic brain injury. J. Neurochem. 93, 1314-1326. doi: 10.1111/j.1471-4159.2005.03127.x
51. Meffre, D., Labombarda, F., Delespierre, B., Chastre, A., De Nicola, A. F., Stein, D. G., et al. (2013). Distribution of membrane progesterone receptor alpha in the male mouse and rat brain and its regulation after traumatic brain injury. Neuroscience 231, 111-124. doi: 10.1016/j.neuroscience.2012.11.039
52. Mellon, S. H., Gong, W., and Schonemann, M. D. (2008). Endogenous and synthetic neurosteroids in treatment of Niemann-Pick Type C disease. Brain Res. Rev. 57, 410-420. doi: 10.1016/j.brainresrev.2007.05.012
53. Mencarelli, A., Migliorati, M., Barbanti, M., Cipriani, S., Palladino, G., Distrutti, E., et al. (2010). Pregnane-X-receptor mediates the anti-inflammatory activities of rifaximin on detoxification pathways in intestinal epithelial cells. Biochem. Pharmacol. 80, 1700-1707. doi: 10.1016/j.bcp.2010.08.022
54. Nin, M. S., Martinez, L. A., Pibiri, F., Nelson, M., and Pinna, G. (2011). Neurosteroids reduce social isolation-induced behavioral deficits: a proposed link with neurosteroid-mediated upregulation of BDNF expression. Front Endocrinol. Lausanne 2:73. doi: 10.3389/fendo.2011.00073
55. Pajovic, S., Saicic, Z. S., Spasic, M. B., Petrovic, V. M., and Martinovic, J. V. (1996). Effect of progesterone and estradiol benzoate on superoxide dismutase activity in the brain of male rats. Experientia 52, 221-224. doi: 10.1007/BF01920710
56. Pang, Y., Dong, J., and Thomas, P. (2013). Characterization, neurosteroid binding and brain distribution of human membrane progesterone receptors δ and ε (mPRδ and mPR?ε) and mPRd involvement in neurosteroid inhibition of apoptosis. Endocrinology 154, 283-295. doi: 10.1210/en.2012-1772
57. Paul, S. M., and Purdy, R. H. (1992). Neuroactive steroids. FASEB J. 6, 2311-2322.
58. Peluso, J. J. (2006). Multiplicity of progesterone's actions and receptors in the mammalian ovary. Biol. Reprod. 75, 2-8. doi: 10.1095/biolreprod.105.049924
59. Pirker, S., Schwarzer, C., Wieselthaler, A., Sieghart, W., and Sperk, G. (2000). GABAA receptors: immunocytochemical distribution of 13 subunits in the adult rat brain. Neuroscience 101, 815-850. doi: 10.1016/S0306-4522(00)00442-5
60. Price, T. (2013). Progesterone receptor membrane component 1: is metabolism integral to its function and what other steroids are involved? Menopause 20, 486-487. doi: 10.1097/GME.0b013e318287f30e
61. ProTECT III. (2009). Progesterone for the Treatment of Traumatic Brain Injury; ClinicalTrials.gov Identifier: NCT00822900. Available online at: http://clinicaltrial.gov/ct2/show/NCT00822900?term=PROTECT+IIIandrank=1
62. Reddy, D. S., Castaneda, D. C., O'Malley, B. W., and Rogawski, M. A. (2004). Anticonvulsant activity of progesterone and neurosteroids in progesterone receptor knockout mice. J. Pharmacol. Exp. Ther. 310, 230-239. doi: 10.1124/jpet.104.065268
63. Reddy, D. S., O'Malley, B. W., and Rogawski, M. A. (2005). Anxiolytic activity of progesterone in progesterone receptor knockout mice. Neuropharmacology 48, 14-24. doi: 10.1016/j.neuropharm.2004.09.002
64. Reddy, D. S., and Zeng, Y. C. (2007). Differential anesthetic activity of ketamine and the GABAergic neurosteroid allopregnanolone in mice lacking progesterone receptor A and B subtypes. Methods Find. Exp. Clin. Pharmacol. 29, 659-664. doi: 10.1358/mf.2007.29.10.1147766
65. Roof, R. L., Duvdevani, R., Braswell, L., and Stein, D. G. (1994). Progesterone facilitates cognitive recovery and reduces secondary neuronal loss caused by cortical contusion injury in male rats. Exp. Neurol. 129, 64-69. doi: 10.1006/exnr.1994.1147
66. Roof, R. L., Duvdevani, R., and Stein, D. G. (1992). Progesterone treatment attenuates brain edema following contusion injury in male and female rats. Restor. Neurol. Neurosci. 4, 425-427. doi: 10.3233/RNN-1992-4608
67. Roof, R. L., Duvdevani, R., and Stein, D. G. (1993). Gender influences outcome of brain injury: progesterone plays a protective role. Brain Res. 607, 333-336. doi: 10.1016/0006-8993(93)91526-X
68. Roof, R. L., Duvdevani, R., and Stein, D. G. (2005). The neuroprotective effect of progesterone after traumatic brain injury in male mice is independent of both the inflammatory response and growth factor expression. Eur. J. Neurosci. 21, 1547-1554. doi: 10.1111/j.1460-9568.2005.03995.x
69. Runko, E., and Kaprielian, Z. (2004). Caenorhabditis elegans VEM-1, a novel membrane protein, regulates the guidance of ventral nerve cord-associated axons. J. Neurosci. 24, 9015-9026. doi: 10.1523/JNEUROSCI.2385-04.2004
70. Rupprecht, R., Reul, J. M., Trapp, T., van Steensel, B., Wetzel, C., Damm, K., et al. (1993). Progesterone receptor-mediated effects of neuroactive steroids. Neuron 11, 523-530. doi: 10.1016/0896-6273(93)90156-L
71. Sakamoto, H., Ukena, K., Takemori, H., Okamoto, M., Kawata, M., and Tsutsui, K. (2004). Expression and localization of 25-Dx, a membrane-associated putative progesterone-binding protein, in the developing Purkinje cell. Neuroscience 126, 325-334. doi: 10.1016/j.neuroscience.2004.04.003
72. Sayeed, I., Parvez, S., Wali, B., Siemen, D., and Stein, D. G. (2009). Direct inhibition of the mitochondrial permeability transition pore: a possible mechanism for better neuroprotective effects of allopregnanolone over progesterone. Brain Res. 1263, 165-173. doi: 10.1016/j.brainres.2009.01.045
73. Sayeed, I., and Stein, D. G. (2009). Progesterone as a neuroprotective factor in traumatic and ischemic brain injury. Prog. Brain Res. 175, 219-237. doi: 10.1016/S0079-6123(09)17515-5
74. Shughrue, P. J., Stumpf, W. E., and Sar, M. (1988). The distribution of progesterone receptor in the 20-day-old fetal mouse: an autoradiographic study with [125I]progestin. Endocrinology 123, 2382-2389. doi: 10.1210/endo-123-5-2382
75. Sleiter, N., Pang, Y., Park, C., Horton, T. H., Dong, J., Thomas, P., et al. (2009). Progesterone receptor A (PRA) and PRB-independent effects of progesterone on gonadotropin-releasing hormone release. Endocrinology 150, 3833-3844. doi: 10.1210/en.2008-0774
76. Stein, D. G. (2012). A clinical/translational perspective: can a developmental hormone play a role in the treatment of traumatic brain injury? Horm. Behav. 63, 291-300. doi: 10.1016/j.yhbeh.2012.05.004
77. Stein, D. G., and Wright, D. W. (2010). Progesterone in the clinical treatment of acute traumatic brain injury. Expert Opin. Investig. Drugs 19, 847-857. doi: 10.1517/13543784.2010.489549
78. Su, C., Cunningham, R. L., Rybalchenko, N., and Singh, M. (2012). Progesterone increases the release of brain-derived neurotrophic factor from glia via progesterone receptor membrane component 1 (Pgrmc1)-dependent ERK5 signaling. Endocrinology 153, 4389-4400. doi: 10.1210/en.2011-2177
79. Thomas, P., and Pang, Y. (2012). Membrane progesterone receptors: evidence for neuroprotective, neurosteroid signaling and neuroendocrine functions in neuronal cells. Neuroendocrinology 96, 162-171. doi: 10.1159/000339822
80. Tubbs, C., and Thomas, P. (2009). Progestin signaling through an olfactory G protein and membrane progestin receptor-alpha in Atlantic croaker sperm: potential role in induction of sperm hypermotility. Endocrinology 150, 473-484. doi: 10.1210/en.2008-0512
81. VanLandingham, J. W., Cutler, S. M., Virmani, S., Hoffman, S. W., Covey, D. F., Krishnan, K., et al. (2006). The enantiomer of progesterone acts as a molecular neuroprotectant after traumatic brain injury. Neuropharmacology 51, 1078-1085. doi: 10.1016/j.neuropharm.2006.07.015
82. Wang, J. M., and Brinton, R. D. (2008). Allopregnanolone-induced rise in intracellular calcium in embryonic hippocampal neurons parallels their proliferative potential. BMC Neurosci. 9:S11. doi: 10.1186/1471-2202-9-S2-S11
83. Wang, J. M., Johnston, P. B., Ball, B. G., and Brinton, R. D. (2005). The neurosteroid allopregnanolone promotes proliferation of rodent and human neural progenitor cells and regulates cell-cycle gene and protein expression. J. Neurosci. 25, 4706-4718. doi: 10.1523/JNEUROSCI.4520-04.2005
84. Wang, M. (2011). Neurosteroids and GABA-A receptor function. Front. Endocrinol. Lausanne 2:44. doi: 10.3389/fendo.2011.00044
85. Wright, D. W., Kellermann, A. L., Hertzberg, V. S., Clark, P. L., Frankel, M., Goldstein, F. C., et al. (2007). ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann. Emerg. Med. 49, 391-402. doi: 10.1016/j.annemergmed.2006.07.932
86. Xiao, G., Wei, J., Yan, W., Wang, W., and Lu, Z. (2008). Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Crit. Care 12:R61. doi: 10.1186/cc6887
87. Zhu, Y., Bond, J., and Thomas, P. (2003a). Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor. Proc. Natl. Acad. Sci. U.S.A. 100, 2237-2242. doi: 10.1073/pnas.0436133100
88. Zhu, Y., Rice, C. D., Pang, Y., Pace, M., and Thomas, P. (2003b). 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. U.S.A. 100, 2231-2236. doi: 10.1073/pnas.0336132100
89. Zucchini, N., de Sousa, G., Bailly-Maitre, B., Gugenheim, J., Bars, R., Lemaire, G., et al. (2005). Regulation of Bcl-2 and Bcl-xL anti-apoptotic protein expression by nuclear receptor PXR in primary cultures of human and rat hepatocytes. Biochim. Biophys. Acta 1745, 48-58. doi: 10.1016/j.bbamcr.2005.02.005
90. Zuloaga, D. G., Yahn, S. L., Pang, Y., Quihuis, A. M., Oyola, M. G., Reyna, A., et al. (2012). Distribution and estrogen regulation of membrane progesterone receptor-ß in the female rat brain. Endocrinology 153, 4432-4443. doi: 10.1210/en.2012-1469