Evaluation of Newly Developed Chemical Castration Method: Changes in Hormone Gene Expression of Hypothalamic-Pituitary Axis
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
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± 1.31:1.34±0.19:1.28±0.18 ng/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±0.06:1:2.07±0.41:1.51±0.37 AU; 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.
Abstract
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± 1.31:1.34±0.19:1.28±0.18 ng/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±0.06:1:2.07±0.41:1.51±0.37 AU; 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.
참고문헌 (34)
- Attar RM, "Castrationresistant prostate cancer: locking up the molecular escape routes", Clin Cancer Res, 15, pp.3251~3255 (2009)
- Castellano JM, "Alterations in hypothalamic KiSS-1 system in experimental diabetes:early changes and functional consequences", Endocrinology, 150, pp.784~794 (2009)
- Costantino A, "Advances in male hormonal contraception", Indian J Med Res, 140, pp.S58~S62 (2014)
- Dalkin AC, "Regulation of gonadotropin subunit gene transcription by gonadotropinreleasing hormone: measurement of primary transcript ribonucleic acids by quantitative reverse transcriptionpolymerase chain reaction assays", Endocrinology, 142, pp.139~146 (2001)
- i signaling patterns in male mouse pituitary gonadotrophs in situ: Studies in the acute pituitary slice preparation, "Biol Reprod", 2013, 1~11
- Emanuele NV, "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, 1996, pp.148, 509~515
- Emir L, "Chemical castration with intratesticular injection of 20% hypertonic saline: A minimally invasive method", Urol Oncol, 26, pp.392~396 (2008)
- Emir L, "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, pp.212~217 (2011)
- Fagundes AK, "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, pp.230~236 (2014)
- Fordyce G, "An evaluation of calf castration by intra-testicular injection of a lactic acid solution", Aust Vet J, 66, pp.272~276 (1989)
- Gore AC, "Glucocorticoid repression of the reproductive axis: Effects on GnRH and gonadotropin subunit mRNA levels", Mol Cell Endocrinol, 256, pp.40~48 (2006)
- Ibrahim A, "Evaluation of chemical castration with calcium chloride versus surgical castration in donkeys: testosterone as an endpoint marker", BMC Vet Res, 12, pp.46~ (2016)
- Inada M, "Animal models for bone and joint disease. Ovariectomized and orchidectomized animals", Clin Calcium, 21, pp.164~170 (2011)
- James P, "Presence of corticotrophin-releasing factor and", or tyrosine hydroxylase in cells of a neural brain-testicular pathway that are labelled by a transganglionic tracer, 2008, pp.20, 173~181
- Jana K, "Evaluation of single intratesticular injection of calcium chloride for nonsurgical sterilization in adult albino rats", Contraception, 73, pp.289~300 (2006)
- Jana K, "Sterilization of male stray dogs with a single intratesticular injection of calcium chloride: A dose-dependent study", Contraception, 75, pp.390~400 (2007)
- Jana K, "Dose-dependent response to an intratesticular injection of calcium chloride for induction of chemosterilization in adult albino rats", Vet Res Commun, 26, pp.651~673 (2002)
- 이중복, "Induction of castration by immunization of male dogs with recombinant gonadotropin-releasing hormone(GnRH)-canine distemper virus(CDV)T helper cell epitope p35", Journal of Veterinary Science, 6(1), pp.21~24 (2005), 대한수의학회
- Kalra PS, "Further studies on the effects of testosterone on hypothalamic LH-RH and serum LH levels:castration-induced delayed response", Neuroendocrinology, 41, pp.219~223 (1985)
- Kalra SP, "Neural regulation of luteinizing hormone secretion in the rat", Endocr Rev, 4, pp.311~351 (1983)
- 곽병국, "Intratesticular Injection of Hypertonic Saline : Non-Invasive Alternative Method for Animal Castration Model", 발생과 생식, 17(4), pp.435~440 (2013), 한국발생생물학회[DOI]
- Leoci R, "Alcohol diluent provides the optimal formulation for calcium chloride non-surgical sterilization in dogs", Acta Vet Scand, 14, pp.56~62 (2014)
- Lightfoot JT, "Sex hormones' regulation of rodent physical activity: A review", Int J Biol Sci, 4, pp.126~132 (2008)
- Neto OA, "Intratesticular hypertonic sodium chloride solution treatment as a method of chemical castration in cattle", Theriogenology, 82, pp.1007~1011 (2014)
- Rhodes L, "New approaches to non-surgical sterilization for dogs and cats: Opportunities and challenges", Reprod Domest Anim, 52(Suppl 2), pp.327~331 (2017)
- Rothfeld JM, "LHRH messenger RNA in neurons in the intact and castrate male rat forebrain, studied by in situ hybridization", Exp Brain Res, 67, pp.113~118 (1987)
- Selvage DJ, "Role played by brainstem neurons in regulating testosterone secretion via a direct neural pathway between the hypothalamus and the testes", Endocrinology, 147, pp.3070~3075 (2006)
- Selvage DJ, "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, pp.594~598 (2003)
- Smith JT, "Differential regulation of KiSS-1 mRNA expression by sex steroids in the brain of the male mouse", Endocrinology, 146, pp.2976~2984 (2005)
- Spratt DP, "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, pp.125~133 (1997)
- Valenti S, "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, pp.381~386 (1997)
- Wiebe JP, "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, pp.291~302 (1984)
- Wiemann JN, "Gonadotropin-releasing hormone messenger ribonucleic acid levels are unaltered with changes in the gonadal hormone milieu of the adult male rat", Endocrinology, 127, pp.523~532 (1990)
- Wu S, "Signaling of cytokines is important in regulation of GnRH neurons", Mol Neurobiol, 45, pp.119~125 (2012)
