한국발생생물학회지:발생과생식 (Development and Reproduction)

  • 제21권3호
  • /
  • Pages.307-315
  • /
  • 2017
  • /
  • 2465-9525(pISSN)
  • /
  • 2465-9541(eISSN)
한국발생생물학회 (The Korean Society of Developmental Biology)
권호 표지
DOI QR코드

DOI QR Code

Evaluation of Newly Developed Chemical Castration Method: Changes in Hormone Gene Expression of Hypothalamic-Pituitary Axis

  • 투고 : 2017.09.17
  • 심사 : 2017.09.22
  • 발행 : 2017.09.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Surgical castration (also known as orchidectomy, ORX) has been frequently performed to avoid uncontrolled breeding. However, it has some serious disadvantages. Several laboratories have developed chemical castration methods, using bilateral intratesticular injection (BITI) of simple chemical solutions. The present study was undertaken to compare the effects of ORX and of hypertonic saline BITI on the androgen-sensitive tissues such as pituitary and hypothalamus. Serum testosterone (T) levels of ORX animals and hypertonic saline BITI animals (SAL) after 4 weeks of the manipulations exhibited significantly drops as compared with the levels of intact animals ( $Intact:ORX:SAL=7.74{\pm}1.31:1.34{\pm}0.19:1.28{\pm}0.18ng/ml$, p<0.001). Both ORX and BITI method induced similar stimulatory effects on the pituitary gonadotropin subunits and hypothalamic KiSS-1 gene expressions. In contrast, the effects of ORX and hypertonic saline BITI on hypothalamic GnRH gene expression were different from these gene expressions, shown an inverse relationship between the two groups ($Intact:ORX:SAL=1:0.45{\pm}0.06:1:2.07{\pm}0.41:1.51{\pm}0.37AU$; ORX, p<0.001; SAL, p<0.05). In conclusion, we provided evidence that hypertonic saline BITI method has equivalent efficacy of T depletion to surgical castration in rats. The present study suggests the hypertonic saline BITI could be a promising substitute to conventional surgical castration.

키워드

참고문헌

  1. Attar RM, Takimoto CH, Gottardis MM (2009) Castrationresistant prostate cancer: locking up the molecular escape routes. Clin Cancer Res 15:3251-3255. https://doi.org/10.1158/1078-0432.CCR-08-1171
  2. Castellano JM, Navarro VM, Roa J, Pineda R, Sanchez-Garrido MA, Garcia-Galiano D, Vigo E, Dieguez C, Aguilar E, Pinilla L, Tena-Sempere M (2009) Alterations in hypothalamic KiSS-1 system in experimental diabetes: early changes and functional consequences. Endocrinology 150:784-794. https://doi.org/10.1210/en.2008-0849
  3. Costantino A, Gava G, Berra M, Meriggiola MC (2014) Advances in male hormonal contraception. Indian J Med Res 140 Suppl:S58-62.
  4. Dalkin AC, Burger LL, Aylor KW, Haisenleder DJ, Workman LJ, Cho S, Marshall JC (2001) Regulation of gonadotropin subunit gene transcription by gonadotropinreleasing hormone: measurement of primary transcript ribonucleic acids by quantitative reverse transcriptionpolymerase chain reaction assays. Endocrinology 142:139-146. https://doi.org/10.1210/endo.142.1.7881
  5. Duran-Pasten ML, Fiordelisio-Coll T, Hernandez-Cruz A (2013) Castration-induced modifications of GnRHelicited $[Ca^{2+}]_{i}$ signaling patterns in male mouse pituitary gonadotrophs in situ: Studies in the acute pituitary slice preparation. Biol Reprod 88:1-11.
  6. Emanuele NV, Jurgens J, La Paglia N, Williams DW, Kelley MR (1996) The effect of castration on steady state levels of luteinizing hormone-releasing hormone (LHRH) mRNA and proLHRH processing: Time course study utilizing semi-quantitative reverse transcription/polymerase chain reaction. J Endocrinol 148:509-515. https://doi.org/10.1677/joe.0.1480509
  7. Emir L, Dadali M, Sunay M, Erol D, Caydere M, Ustu H (2008) Chemical castration with intratesticular injection of 20% hypertonic saline: A minimally invasive method. Urol Oncol 26:392-396. https://doi.org/10.1016/j.urolonc.2007.05.013
  8. Emir L, Sunay M, YalbuzdagO, Karakaya Y, Erol D (2011) Hormonal and pathologic changes after chemoablation of testes with hypertonic saline solution as a treatment method alternative to orchiectomy in patients with hormone sensitive metastatic prostatic cancer. Urol Oncol 29:212-217. https://doi.org/10.1016/j.urolonc.2008.12.021
  9. Fagundes AK, Oliveira EC, Tenorio BM, Melo CC, Nery LT, Santos FA, Alves LC, Douglas RH, Silva VA Jr (2014) Injection of a chemical castration agent, zinc gluconate, into the testes of cats results in the impairment of spermatogenesis: A potentially irreversible contraceptive approach for this species? Theriogenology 81:230-236. https://doi.org/10.1016/j.theriogenology.2013.09.013
  10. Fordyce G, Hodge PB, Beaman NJ, Laing AR, Campero C, Shepherd RK (1989) An evaluation of calf castration by intra-testicular injection of a lactic acid solution. Aust Vet J 66:272-276. https://doi.org/10.1111/j.1751-0813.1989.tb13950.x
  11. Gore AC, Attardi B, DeFranco DB (2006) Glucocorticoid repression of the reproductive axis: Effects on GnRH and gonadotropin subunit mRNA levels. Mol Cell Endocrinol 256:40-48. https://doi.org/10.1016/j.mce.2006.06.002
  12. Ibrahim A, Ali MM, Abou-Khalil NS, Ali MF (2016) Evaluation of chemical castration with calcium chloride versus surgical castration in donkeys: testosterone as an endpoint marker. BMC Vet Res 12:46 https://doi.org/10.1186/s12917-016-0670-3
  13. Inada M, Matsumoto C, Miyaura C (2011) Animal models for bone and joint disease. Ovariectomized and orchidectomized animals. Clin Calcium 21:164-170.
  14. James P, Rivier C, Lee S (2008) Presence of corticotrophin-releasing factor and/or tyrosine hydroxylase in cells of a neural brain-testicular pathway that are labelled by a transganglionic tracer. J Neuroendocrinol 20:173-181.
  15. Jana K, Samanta PK (2006) Evaluation of single intratesticular injection of calcium chloride for nonsurgical sterilization in adult albino rats. Contraception 73:289-300. https://doi.org/10.1016/j.contraception.2005.07.011
  16. Jana K, Samanta PK (2007) Sterilization of male stray dogs with a single intratesticular injection of calcium chloride: A dose-dependent study. Contraception 75:390-400. https://doi.org/10.1016/j.contraception.2007.01.022
  17. Jana K, Samanta PK, Ghosh D (2002) Dose-dependent response to an intratesticular injection of calcium chloride for induction of chemosterilization in adult albino rats. Vet Res Commun 26:651-673. https://doi.org/10.1023/A:1020976905746
  18. Jung MJ, Moon YC, Cho IH, Yeh JY, Kim SE, Chang WS, Park SY, Song CS, Kim HY, Park KK, McOrist S, Choi IS, Lee JB (2005) Induction of castration by immunization of male dogs with recombinant gonadotropin releasing hormone (GnRH)-canine distemper virus (CDV) T helper cell epitope p35. J Vet Sci 6:21-24.
  19. Kalra PS (1985) Further studies on the effects of testosterone on hypothalamic LH-RH and serum LH levels: castration-induced delayed response. Neuroendocrinology 41:219-223. https://doi.org/10.1159/000124188
  20. Kalra SP, Kalra PS (1983) Neural regulation of luteinizing hormone secretion in the rat. Endocr Rev 4:311-351. https://doi.org/10.1210/edrv-4-4-311
  21. Kwak BK, Lee S-H (2013) Intratesticular injection of hypertonic saline; non-invasive alternative method for animal castration model. Dev Reprod 17:435-440. https://doi.org/10.12717/DR.2013.17.4.435
  22. Leoci R, Aiudi G, Silvestre F, Lissner EA, Lacalandra GM (2014) Alcohol diluent provides the optimal formulation for calcium chloride non-surgical sterilization in dogs. Acta Vet Scand 14;56-62.
  23. Lightfoot JT (2008) Sex hormones' regulation of rodent physical activity: A review. Int J Biol Sci 4:126-132.
  24. Neto OA, Gasperin BG, Rovani MT, Ilha GF, Nobrega JE Jr, Mondadori RG, Goncalves PB, Antoniazzi AQ (2014) Intratesticular hypertonic sodium chloride solution treatment as a method of chemical castration in cattle. Theriogenology 82:1007-1011. https://doi.org/10.1016/j.theriogenology.2014.07.020
  25. Rhodes L (2017) New approaches to non-surgical sterilization for dogs and cats: Opportunities and challenges. Reprod Domest Anim 52 Suppl 2:327-331.
  26. Rothfeld JM, Hejtmancik JF, Conn PM, Pfaff DW (1987) LHRH messenger RNA in neurons in the intact and castrate male rat forebrain, studied by in situ hybridization. Exp Brain Res 67:113-118. https://doi.org/10.1007/BF00269459
  27. Selvage DJ, Parsons L, Rivier C (2006) Role played by brainstem neurons in regulating testosterone secretion via a direct neural pathway between the hypothalamus and the testes. Endocrinology 147:3070-3075. https://doi.org/10.1210/en.2005-1358
  28. Selvage DJ, Rivier C (2003) Importance of the paraventricular nucleus of the hypothalamus as a component of a neural pathway between the brain and the testes that modulates testosterone secretion independently of the pituitary. Endocrinology 144:594-598. https://doi.org/10.1210/en.2002-220781
  29. Smith JT, Dungan HM, Stoll EA, Gottsch ML, Braun RE, Eacker SM, Clifton DK, Steiner RA (2005) Differential regulation of KiSS-1 mRNA expression by sex steroids in the brain of the male mouse. Endocrinology 146:2976-2984. https://doi.org/10.1210/en.2005-0323
  30. Spratt DP, Herbison AE (1997) Regulation of preoptic area gonadotrophin-releasing hormone (GnRH) mRNA expression by gonadal steroids in the long-term gonadectomized male rat. Brain Res Mol Brain Res 47:125-133. https://doi.org/10.1016/S0169-328X(97)00037-5
  31. Valenti S, Sarkissian A, Giusti M, Giordano G, Dahl KD (1997) Immunoreactive and bioactive LH release from pituitaries of intact or castrated male rats: effect of in vitro GnRH and KCl administration. J Endocrinol Invest 20:381-386. https://doi.org/10.1007/BF03347988
  32. Wiebe JP, Barr KJ (1984) The control of male fertility by 1,2,3-trihydroxypropan (THP; glycerol): rapid arrest of spermatogenesis without altering libido, accessory organs, gonadal steroidogenesis and serum testosterone. LH and FSH. Contraception 29:291-302. https://doi.org/10.1016/S0010-7824(84)80009-8
  33. Wiemann JN, Clifton DK, Steiner RA (1990) Gonadotropin-releasing hormone messenger ribonucleic acid levels are unaltered with changes in the gonadal hormone milieu of the adult male rat. Endocrinology 127:523-532.
  34. Wu S, Wolfe A (2012) Signaling of cytokines is important in regulation of GnRH neurons. Mol Neurobiol 45:119-125. https://doi.org/10.1007/s12035-011-8224-y