A pelvic trinity: prostate, hormones and nerves

Main Article Content

Victor Hugo Cruz-Rivas Jorge Manzo-Denes Fausto Rojas-Durán Emiliano Gonzalo Aranda-Abreu Deissy Herrera-Covarrubias Jorge Suárez-Medellin Isauro Luis García-Hernández María Elena Hernández-Aguilar

Abstract

The prostate is an accessory sex gland responsible for producing and excreting prostate fluid. In the male rat, hormones such as testosterone (T) and prolactin (PRL) and the pelvic and hypogastric nerves regulate the gland, providing afferent information and adrenergic and cholinergic innervation to the prostate. Damages in the innervation or alterations in the hormonal levels of T and PRL changes the prostate’s cytoarchitecture and function that can promote the presence of cancer. However, sexual activity delays effects induced by hormonal alterations or dysfunction of the autonomic nervous system, but it does not mean that they do not appear since the cases of death from prostate cancer is still increasing. That is why this review has the fundamental purpose of showing the relationship between the hormones, autonomic nervous system, and sexual behavior in the pathophysiology of the prostate, with the ultimate aim of trying to understand the role that each one plays in diseases of the prostate. To date, results show that morphological changes in the prostate correlate with an increase in prolactin serum levels, a decrease in androgen and long prolactin receptors, and an increase in short prolactin receptors. Also, damage in the innervation induces an increase in androgen and muscarinic receptors in the major pelvic ganglia that supply the nerves that control the prostate in animal with sexual experience.

Article Details

How to Cite
CRUZ-RIVAS, Victor Hugo et al. A pelvic trinity: prostate, hormones and nerves. Medical Research Archives, [S.l.], v. 10, n. 2, feb. 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2669>. Date accessed: 06 dec. 2022. doi: https://doi.org/10.18103/mra.v10i2.2669.
Section
Research Articles

References

1. Manzo J, García LI, Coria GA. Control autonómico de la conducta sexual masculina. In: Manzo J, ed. La Década Del Cerebro y La Conducta Sexula. Neuroetología. Primera ed. Universidad Veracruzana; 2002:73-87.
2. Hernandez ME, Soto-Cid A, Aranda-Abreu GE, et al. A study of the prostate, androgens and sexual activity of male rats. Reprod Biol Endocrinol. 2007;5(11):1-9. doi:10.1186/1477-7827-5-11
3. Kepper M, Keast J. Immunohistochemical properties and spinal connections of pelvic autonomic neurons that innervate the rat prostate gland. Cell Tissue Res. 1995;281(3):533-542. doi:10.1007/BF00417871
4. Tlachi-López JL, López A, Hoffman K, Velázquez-Moctezuma J, García-Lorenzana M, Lucio RA. Rat dorsal prostate is necessary for vaginal adhesion of the seminal plug and sperm motility in the uterine horns. Biol Res. 2011;44(3):259-267. doi:10.4067/S0716-97602011000300007
5. Dail WG, Evan AP, Eason HR. The major ganglion in the pelvic plexus of the male rat - A histochemical and ultrastructural study. Cell Tissue Res. 1975;159(1):49-62. doi:10.1007/BF00231994
6. Lucio RA, Manzo J, Martínez-Gómez M, Sachs BD, Pacheco P. Participation of pelvic nerve branches in male rat copulatory behavior. Physiol Behav. 1994;55(2):241-246. doi:10.1016/0031-9384(94)90129-5
7. Keast JR, Booth AM, de Groat WC. Distribution of neurons in the major pelvic ganglion of the rat which supply the bladder, colon or penis. Cell Tissue Res. 1989;256(1):105-112. doi:10.1007/BF00224723
8. Wang JM, McKenna KE, McVary KT, Lee C. Requirement of innervation for maintenance of structural and functional integrity in the rat prostate. Biol Reprod. 1991;44(6):1171-1176. doi:10.1095/biolreprod44.6.1171
9. Diaz R, Garcia LI, Locia J, et al. Histological modifications of the rat prostate following transection of somatic and autonomic nerves. An Acad Bras Cienc. 2010;82(2):397-404. doi:10.1590/S0001-37652010000200015
10. Sánchez V. Efecto de la conducta sexual y la denervación preganglionar sobre las características histológicas de la próstata y del gánglio pélvido mayor en la rata. Published online 2021.
11. Marx FJ, Karenberg A. History of the term prostate. Prostate. 2009;69(2):208-213. doi:10.1002/pros.20871
12. Hernández ME, Muñoz DA, Cocotle ML, Serrano MK. La próstata: tu compañera de vida. In: Vázquez E, Toledo MR, Hernández ME, Manzo J, eds. 10 Años Celebrando Al Cerebro. Primera. Universidad Veracruzana; 2017:96-99.
13. Price D. Comparative aspects of development and structure in the prostate. Natl Cancer Inst Monogr. 1963;12:1-27. Accessed November 15, 2021. https://pubmed.ncbi.nlm.nih.gov/14072991/
14. Wendell-Smith C. Terminology of the prostate and related structures. Clin Anat. 2000;13(3):207-213. doi:10.1002/(SICI)1098-2353(2000)13:3<207::AID-CA9>3.0.CO;2-9
15. Dauge MC, Delmas V, Potier M. The anatomic lobulation of the prostate, a controversial description. Morphologie. 1999;83(260):5-14. Accessed December 2, 2021. https://pubmed.ncbi.nlm.nih.gov/10417987/
16. Timms BG. Prostate development: A historical perspective. Differentiation. 2008;76(6):565-577. doi:10.1111/j.1432-0436.2008.00278.x
17. Hayward SW, Cunha GR. The prostate: Development and physiology. Radiol Clin North Am. 2000;38(1):1-14. doi:10.1016/S0033-8389(05)70146-9
18. Timms BG, Hofkamp LE. Prostate development and growth in benign prostatic hyperplasia. Differentiation. 2011;82(4-5):173-183. doi:10.1016/j.diff.2011.08.002
19. Villers A, Steg A, Boccon-Gibod L. Anatomy of the prostate: Review of the different models. Eur Urol. 1991;20(4):261-268. doi:10.1159/000471714
20. Jesik CJ, Holland JM, Lee C. An anatomic and histologic study of the rat prostate. Prostate. 1982;3:81-97. http://www.ncbi.nlm.nih.gov/pubmed/10588249
21. Oliveira DSM, Dzinic S, Bonfil AI, Saliganan AD, Sheng S, Bonfil RD. The mouse prostate: A basic anatomical and histological guideline. Bosn J Basic Med Sci. 2016;16(1):8-13. doi:10.17305/bjbms.2016.917
22. Wang G, Zhao D, Spring DJ, Depinho RA. Genetics and biology of prostate cancer. Genes Dev. 2018;32(17-18):1105-1140. doi:10.1101/gad.315739.118
23. Ittmann M. Anatomy and histology of the human and murine prostate. Cold Spring Harb Perspect Med. 2017;8(5):1-6. doi:10.1101/cshperspect.a030346
24. Lee CH, Akin-Olugbade O, Kirschenbaum A. Overview of prostate anatomy, histology, and pathology. Endocrinol Metab Clin North Am. 2011;40(3):565-575. doi:10.1016/j.ecl.2011.05.012
25. Pascual-Mathey LI, Rojas-Duran F, Aranda-Abreu GE, et al. Effect of hyperprolactinemia on PRL-receptor expression and activation of Stat and Mapk cell signaling in the prostate of long-term sexually-active rats. Physiol Behav. 2016;157(73):170-177. doi:10.1016/j.physbeh.2016.02.011
26. Verze P, Cai T, Lorenzetti S. The role of the prostate in male fertility, health and disease. Nat Rev Urol. 2016;13(7):379-386. doi:10.1038/nrurol.2016.89
27. Charalabopoulos K, Karachalios G, Baltogiannis D, Charalabopoulos A, Giannakopoulos X, Sofikitis N. Penetration of antimicrobial agents into the prostate. Chemotherapy. 2003;49(6):269-279. doi:10.1159/000074526
28. Jha SK, Rauniyar K, Chronowska E, Mattonet K, Alitalo K, Jeltsch M. KLK3/PSA and cathepsin D activate VEGF-C and VEGF-D. Elife. 2019;1:1-30. https://doi.org/10.7554/eLife.44478.001
29. Díaz R. Efecto de la denervación hipogástrica sobre la densidad de catepsina D en ratas sometidas a conducta sexual y estimulación a distancia. Published online 2015.
30. Gilany K, Minai-Tehrani A, Savadi-Shiraz E, Rezadoost H, Lakpour N. Exploring the human seminal plasma proteome: An unexplored gold mine of biomarker for male Infertility and male reproduction disorder. J Reprod Infertil. 2015;16(2):61-71.
31. Herrera-Covarrubias D, Coria-Ávila GA, Chavarría-Xicoténcatl P, et al. Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats. Exp Oncol. 2015;37(1):13-18.
32. Navarro X. Physiology of the autonomic nervous system. Rev Neurol. 2002;35(6):553-562. doi:10.33588/rn.3506.2002013
33. White CW, Xie JH, Ventura S. Age-related changes in the innervation of the prostate gland: Implications for prostate cancer initiation and progression. Organogenesis. 2013;9(3):206-215. doi:10.4161/org.24843
34. Rojas-Durán F. Influencia de la prolactina y las hormonas sexuales esteroideas sobre la morfología e histología prostática en la rata. Published online 2005.
35. Wilson JD, Griffin JE, Russell DW. Steroid 5α-Reductase 2 Deficiency. Endocr Rev. 1993;14(5):577-593. doi:10.1016/B978-0-12-416006-4.00014-4
36. Cunha GR, Donjacour AA, Cooke PS, et al. The endocrinology and developmental biology of the prostate. Endocr Rev. 1987;8(3):338-362. doi:10.1210/edrv-8-3-338
37. Shapiro E, Steiner MS. The embryology and development of the prostate. In: Lepor H, ed. Prostatic Diseases. W.B. Saunders Company; 2000:1-16.
38. Costello LC, Franklin RB. Testosterone and prolactin regulation of metabolic genes and citrate metabolism of prostate epithelial cells. Horm Metab Res. 2002;34(8):417-424. doi:10.1055/s-2002-33598
39. Bonkhoff H, Remberger K. Differentiation pathways and histogenetic aspects of normal and abnormal prostatic growth: A stem cell model. Prostate. 1996;28(2):98-106. doi:10.1002/(SICI)1097-0045(199602)28:2<98::AID-PROS4>3.0.CO;2-J
40. Henttu P, Vihko P. Steroids inversely affect the biosynthesis and secretion of human prostatic acid phosphatase and prostate-specific antigen in the LNCaP cell line. J Steroid Biochem Molec Biol. 1992;41(3):349-360.
41. Fang J, Chung YW, Clemens LG. Relation of Fos-IR expression in the pelvic ganglion to sexual behavior in laboratory rats. Behav Neurosci. 2000;114(3):543-552. doi:10.1037/0735-7044.114.3.543
42. Rodríguez JF, Bernal B, Gutiérrez AG. Estrés, miedo, ansiedad y depresión. In: Coria GA, ed. Neurofisiología de La Conducta. Cerebro y Comportamiento. Primera ed. Universidad Veracruzana; 2015:247-316.
43. Kamel F, Mock EJ, Wright WW, Frankel AI. Alterations in plasma concentrations of testosterone, LH, and prolactin associated with mating in the male rat. Horm Behav. 1975;6(3):277-288. doi:10.1016/0018-506X(75)90014-8
44. Hernandez M, Soto-Cid A, Rojas F, et al. Prostate response to prolactin in sexually active male rats. Reprod Biol Endocrinol. 2006;4(28):1-12. doi:10.1186/1477-7827-4-28
45. Lawrence MG, Lai J, Clements JA. Kallikreins on steroids: Structure, function, and hormonal regulation of prostate-specific antigen and the extended kallikrein locus. Endocr Rev. 2010;31(4):407-446. doi:10.1210/er.2009-0034
46. Lozano JR. Male Accessory Glands and Sperm Function. Spermatozoa - Facts Perspect. Published online 2018:101-116. doi:10.5772/intechopen.74321
47. Costello LC, Franklin RB. Novel role of zinc in the regulation of prostate citrate metabolism and its implications in prostate cancer. Prostate. 1998;35(4):285-296. doi:10.1002/(SICI)1097-0045(19980601)35:4<285::AID-PROS8>3.0.CO;2-F
48. Costello LC, Franklin RB. Effect of prolactin on the prostate. Prostate. 1994;24:162-166.
49. Camargo ACL, Constantino FB, Santos SAA, et al. Influence of postnatal prolactin modulation on the development and maturation of ventral prostate in young rats. Reprod Fertil Dev. 2018;30(7):969-979. doi:10.1071/RD17343
50. Van Coppenolle F, Skryma R, Ouadid-Ahidouch H, et al. Prolactin stimulates cell proliferation through a long form of prolactin receptor and K+ channel activation. Biochem J. 2004;377:569-578.
51. Thomas JA, Keenan EJ. Prolactin influences upon androgen action in male accessory sex organs. Adv Sex Horm Res. 1976;2:425-470. Accessed November 16, 2021. https://pubmed.ncbi.nlm.nih.gov/189591/
52. Heinlein CA, Chang C. Androgen receptor in prostate cancer. Endocr Rev. 2004;25(2):276-308. doi:10.1210/er.2002-0032
53. Costello LC, Liu Y, Zou J, Franklin RB. Evidence for a zinc uptake transporter in human prostate cancer cells which is regulated by prolactin and testosterone. J Biol chmeistry. 1999;274(25):17499-17504. doi:10.1074/jbc.274.25.17499
54. Itaya PW, Thompson SA, Heidger PM. Hormonal effects on zinc concentration and morphology of rat lateral prostate gland. Prostate. 1984;5(5):513-530. doi:10.1002/pros.2990050507
55. Liu Y, Franklin RB, Costello LC. Prolactin and testosterone regulation of mitochondrial zinc in prostate epithelial cells. Prostate. 1997;30(1):26-32. doi:10.1002/(SICI)1097-0045(19970101)30:1<26::AID-PROS4>3.0.CO;2-J
56. Costello LC, Franklin RB. A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer. Arch Biochem Biophys. 2016;611:100-112. doi:10.1016/j.abb.2016.04.014.A
57. Tališman S, Cvitković P, Jurasović J, Pizent A, Gavella M, Ročić B. Semen quality and reproductive endocrine function in relation to biomarkers of lead, cadmium, zinc, and copper in men. Environ Health Perspect. 2000;108(1):45-53. doi:10.1289/ehp.0010845
58. Farag AGA, Basha MA, Amin SA, et al. Tramadol (opioid) abuse is associated with a dose- and time-dependent poor sperm quality and hyperprolactinaemia in young men. Andrologia. 2018;50(6):1-10. doi:10.1111/and.13026
59. Egwurugwu JN, Ifedi CU, Uchefuna RC, Ezeokafor EN, Alagwu EA. Effects of zinc on male sex hormones and semen quality in rats. Niger J Physiol Sci. 2013;28(1):17-22. Accessed November 17, 2021. https://pubmed.ncbi.nlm.nih.gov/23955401/
60. Wen S, Chang HC, Tian J, Shang Z, Niu Y, Chang C. Stromal androgen receptor roles in the development of normal prostate, benign prostate hyperplasia, and prostate cancer. Am J Pathol. 2015;185(2):293-301. doi:10.1016/j.ajpath.2014.10.012
61. Sarkar S, Das S. A Review of Imaging Methods for Prostate Cancer Detection. Biomed Eng Comput Biol. 2016;7(S1):1-15. doi:10.4137/becb.s34255
62. Banerjee PP, Banerjee S, Brown TR, Zirkin BR. Androgen action in prostate function and disease. Am J Clin Exp Urol. 2018;6(2):62-77. http://www.ncbi.nlm.nih.gov/pubmed/29666834%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5902724
63. Deb S, Chin MY, Pham S, et al. Steroidogenesis in peripheral and transition zones of human prostate cancer tissue. Int J Mol Sci. 2021;22(2):1-16. doi:10.3390/ijms22020487
64. Corona G, Baldi E, Maggi M. Androgen regulation of prostate cancer : Where are we now ? J Endocrinol Invest. 2011;34:232-243. doi:10.3275/7501
65. Ruffion A, Al-Sakkaf KA, Brown BL, Eaton CL, Hamdy FC, Dobson PRM. The survival effect of prolactin on PC3 prostate cancer cells. Eur Urol. 2003;43(3):301-308. doi:10.1016/S0302-2838(03)00038-1
66. Kelly PA, Djiane J, Edery M. The Prolactin/Growth Hormone Receptor Family. Endocr Rev. 1991;12(3):235-251.
67. Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA. Prolactin (PRL) and its receptor: actionm signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev. 1998;19(3):225-268. doi:10.1210/edrv.19.3.0334
68. Hoefer J, Kern J, Ofer P, et al. SOCS2 correlates with malignancy and exerts growth-promoting effects in prostate cancer. Endocr Relat Cancer. 2014;21(2):175-187. doi:10.1530/ERC-13-0446
69. Grayhack JT, Bunce PL, Kearns JW, Scott WW. Influence of the pituitary on prostatic response to androgen in the rat. Bull Johns Hopkins Hosp. 1955;96(4):154-163. Accessed November 18, 2021. https://pubmed.ncbi.nlm.nih.gov/14364007/
70. Hejmej A, Bilinska B. The effects of flutamide on cell-cell junctions in the testis, epididymis, and prostate. Reprod Toxicol. 2018;81(6):1-16. doi:10.1016/j.reprotox.2018.06.014
71. Goffin V. Prolactin receptor targeting in breast and prostate cancers: New insights into an old challenge. Pharmacol Ther. 2017;179:111-126. doi:10.1016/J.PHARMTHERA.2017.05.009
72. Costello LC, Franklin RB. Testosterone, prolactin, and oncogenic regulation of the prostate gland. A new concept: Testosterone-independent malignancy is the development of prolactin-dependent malignancy! Oncol Rev. 2018;12(2):74-82. doi:10.4081/oncol.2018.356
73. Dagvadorj A, Collins S, Jomain JB, et al. Autocrine prolactin promotes prostate cancer cell growth via Janus kinase-2-signal transducer and activator of transcription-5a/b signaling pathway. Endocrinology. 2007;148(7):3089-3101. doi:10.1210/en.2006-1761
74. Holstege G. Central nervous system control of micturition. In: Paxinos G, ed. The Rat Nervous System. Third Edit. Elsevier Academic Press; 2004:321-331.
75. Catala M, Kubis N. Gross anatomy and development of the peripheral nervous system. In: Said G, Krarup C, eds. Handbook of Clinical Neurology. Third Edit. Elsevier B.V.; 2013:29-41.
76. Serrano MK. Efecto de la denervación hipogástrica y/o pélvica sobre la expresión de ARN mensajero de receptores a andrógenos en lóbulo ventral de próstata de rata. Published online January 7, 2013.
77. Dowling P, Ranson RN, Santer RM. Age-associated changes in distribution of the P2X2 receptor in the major pelvic ganglion of the male rat. Neurosci Lett. 2006;404(3):320-323. doi:10.1016/j.neulet.2006.06.001
78. Forrest SL, Payne SC, Keast JR, Osborne PB. Peripheral injury of pelvic visceral afferent nerves alters GFRα (GDNF family receptor alpha) localization in afferent and autonomic pathways of the sacral spinal cord. Front Neuroanat. 2015;9(43):1-13. doi:10.3389/fnana.2015.00043
79. Helen P, Panula P, Yang H-YT, Rapoport SI. Bombesin/gastrin-releasing peptide (GRP)- and Met5-enkephalin-Arg6-G1y7-Leu8-like immunoreactivities in small intensely fluorescent (SIF) cells and nerve fibers of rat sympathetic ganglia. J Histochem Cytochem. 1984;32(11):1131-1138.
80. Aldahmash A, Atteya M. Ganglionectomy in the adult male rat increases neuronal size and synaptic density in remaining contralateral major pelvic ganglion. Currrent Neurobiol. 2011;2(1):5-15.
81. Melvin JE, Hamill RW. Androgen-Specific Critical Periods for the Organization of the Major Pelvic Ganglion. J Neurosci. 1989;9(2):738-742.
82. McVary KT, Razzaq A, Lee C, Venegas MF, Rademaker A, McKenna KE. Growth of the rat prostate gland is facilitated by the autonomic nervous system. Biol Reprod. 1994;51(1):99-107. doi:10.1095/biolreprod51.1.99
83. Serrano MK. Efecto de la denervación hipogástrica y/o pélvica sobre la expresión de receptores a andrógenos, adrenérgicos, colinérgicos y los niveles de testosterona sérica en próstata de rata. Published online 2018.
84. Magnon C, Hall SJ, Lin J, et al. Autonomic nerve development contributes to prostate cancer progression. Science (80- ). 2013;341:1-10. www.sciencemag.org
85. Grytli HH, Fagerland MW, Fosså SD, Taskén KA. Association between use of β-blockers and prostate cancer-specific survival: A cohort study of 3561 prostate cancer patients with high-risk or metastatic disease. Eur Urol. 2014;65(3):635-641. doi:10.1016/j.eururo.2013.01.007
86. Witte LPW, Chapple CR, de la Rosette JJMCH, Michel MC. Cholinergic Innervation and Muscarinic Receptors in the Human Prostate. Eur Urol. 2008;54(2):326-334. doi:10.1016/j.eururo.2007.12.007
87. Rider JR, Wilson KM, Sinnott JA, Kelly RS, Mucci LA, Giovannucci EL. Ejaculation frequency and risk of prostate cancer: Updated results with an additional decade of follow-up. Eur Urol. 2016;70(6):974-982. doi:10.1016/j.eururo.2016.03.027
88. Hernández-Aguilar ME, Serrano MK, Pérez F, et al. Quantification of neural and hormonal receptors at the prostate of long-term sexual behaving male rats after lesion of pelvic and hypogastric nerves. Physiol Behav. 2020;222:1-11. doi:10.1016/j.physbeh.2020.112915
89. Dubeykovskaya Z, Si Y, Chen X, et al. Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer. Nat Commun. 2016;7(10517):1-11. doi:10.1038/ncomms10517
90. Thaker PH, Han LY, Kamat AA, et al. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med. 2006;12(8):939-944. doi:10.1038/nm1447
91. Ayala GE, Dai H, Powell M, et al. Cancer-related axonogenesis and neurogenesis in prostate cancer. Clin Cancer Res. 2008;14(23):7593-7603. doi:10.1158/1078-0432.CCR-08-1164
92. Rodríguez-López MR, Baluja-Conde IB, Bermúdez-Velásquez S. Patologías benignas de la próstata: prostatitis e hiperplasia benigna. Rev Biomed. 2007;18(1):47-59.
93. Portillo W, Paredes R. Conducta Sexual. Vol 12. Primera ed. (Tonda J, Chávez N, eds.). Dirección General de Divulgación de la Ciencia-UNAM; 2010.
94. Manzo J, Miquel M, Toledo R, et al. Fos expression at the cerebellum following non-contact arousal and mating behavior in male rats. Physiol Behav. 2008;93(1-2):357-363. doi:10.1016/j.physbeh.2007.09.005
95. Agmo A, Fernández H. Dopamine and sexual behavior in the male rat: a reevaluation. J Neural Transm. 1989;77:21-37. doi:10.1037/14200-005
96. Arce VM, Catalina PF, Mallo F. Endocrinología. Universidad de Santiago de Compostela; 2006.
97. Rojas-Durán F, Herrera-Ortega L, Aranda-Abreu GE, et al. Prolactin promotes migration in LNCaP prostate cancer cells. eNeurobiologia. 2017;8(19):1-9.
98. Hernandez M, Wilson M. The role of prolactin in the evolution of prostate cancer. Open J Urol. 2012;2(23):188-197. doi:10.4236/oju.2012.223034
99. Humeau Y, Vitale N, Chasserot-Golaz S, et al. A role for phospholipase D1 in neurotransmitter release. Proc Natl Acad Sci U S A. 2001;98(26):15300-15305. doi:10.1073/pnas.261358698
100. Rodrigues AO, Machado MT, Wroclawski ER. Prostate innervation and local anesthesia in prostate procedures. Rev Hosp Clin Fac Med Sao Paulo. 2002;57(6):287-292. doi:10.1590/S0041-87812002000600008
101. OMS. Cáncer. Published 2021. Accessed September 21, 2021. https://www.who.int/es/news-room/fact-sheets/detail/cancer#
102. Mateos A. Efecto de la conducta sexual y la denervación pélvica y/o hipogástrica sobre la expresión de receptores adrenérgicos, colinérgicos, andrógenos y prolactina en el ganglio pélvico mayor de la rata macho. Published online 2021.
103. March B, Faulkner S, Jobling P, et al. Tumour innervation and neurosignalling in prostate cancer. Nat Rev Urol. 2020;17(2):119-130. doi:10.1038/s41585-019-0274-3
104. Tibensky M, Mravec B. Role of the parasympathetic nervous system in cancer initiation and progression. Clin Transl Oncol. 2021;23(4):669-681. doi:10.1007/s12094-020-02465-w
105. Sejda A, Sigorski D, Gulczyński J, Wesołowski W, Kitlińska J, Iżycka-Świeszewska E. Complexity of neural component of tumor microenvironment in prostate cancer. Pathobiology. 2020;87(2):1-13. doi:10.1159/000505437
106. Fernández E V, Price DK, Figg WD. Prostate cancer progression attributed to autonomic nerve development. Potential for therapeutic prevention of localized and metastatic disease. Cancer Biol Ther. 2013;14(11):1005-1006. doi:10.4161/cbt.26339