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

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          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.

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          Differential regulation of KiSS-1 mRNA expression by sex steroids in the brain of the male mouse.

          Kisspeptins are products of the Kiss1 gene, which bind to GPR54, a G protein-coupled receptor. Kisspeptins and GPR54 have been implicated in the neuroendocrine regulation of GnRH secretion. To test the hypothesis that testosterone regulates Kiss1 gene expression, we compared the expression of KiSS-1 mRNA among groups of intact, castrated, and castrated/testosterone (T)-treated male mice. In the arcuate nucleus (Arc), castration resulted in a significant increase in KiSS-1 mRNA, which was completely reversed with T replacement, whereas in the anteroventral periventricular nucleus, the results were the opposite, i.e. castration decreased and T increased KiSS-1 mRNA expression. In the Arc, the effects of T on KiSS-1 mRNA were completely mimicked by estrogen but only partially mimicked by dihydrotestosterone, a nonaromatizable androgen, suggesting that both estrogen receptor (ER) and androgen receptor (AR) play a role in T-mediated regulation of KiSS-1. Studies of the effects of T on KiSS-1 expression in mice with either a deletion of the ERalpha or a hypomorphic allele to the AR revealed that the effects of T are mediated by both ERalpha and AR pathways, which was confirmed by the presence of either ERalpha or AR coexpression in most KiSS-1 neurons in the Arc. These observations suggest that KiSS-1 neurons in the Arc, whose transcriptional activity is inhibited by T, are targets for the negative feedback regulation of GnRH secretion, whereas KiSS-1 neurons in the anteroventral periventricular nucleus, whose activity is stimulated by T, may mediate other T-dependent processes.
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            Castration-resistant prostate cancer: locking up the molecular escape routes.

            The understanding of the key role that androgens play on the normal and pathological physiology of the prostate guided the development of different therapies for the treatment of locally advanced or metastatic prostate cancer (PCa). These so-called androgen deprivation therapies include surgical or chemical castration, achieved by the administration of gonadotropin-releasing hormone analogs; inhibition of steroidogenic enzymes; and finally, blocking of the binding of androgens to their receptor (AR) by the use of antiandrogens. Despite an excellent initial response, in approximately 2 to 3 years, most of these patients will succumb to the castration resistant form of the disease. Remarkably, even in the presence of castration levels of circulating androgens, these tumors are still dependent on a functional AR, and several molecular mechanisms have been proposed to explain this phenomenon. These include: (1) gene amplification and increased expression of the AR mRNA and protein, (2) selection of mutations in the AR that confer broader ligand specificity, (3) changes in the ratios or expression between the AR and its coregulators, (4) increased expression of steroidogenic enzymes, and (5) up-regulation of cross-talk signal transduction pathways that can activate the AR in a ligand-independent manner. We will summarize how these molecular hypotheses are being tested in the clinic by the latest therapeutic modalities.
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              Sex Hormones' Regulation of Rodent Physical Activity: A Review

              There is a large body of emerging literature suggesting that physical activity is regulated to a varying extent by biological factors. Available animal data strongly suggests that there is a differential regulation of physical activity by sex and that the majority of this differential regulation is mediated by estrogen/testosterone pathways with females in many animal species having higher daily activity levels than males. The purpose of this manuscript is to review the mechanisms by which estrogen, progesterone, and testosterone affect the regulation of physical daily activity. This review lays the foundation for future investigations in humans as well as discussions about relative disease risk mediated by differential biological regulation of physical activity by sex.
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                Author and article information

                Journal
                Dev Reprod
                Dev Reprod
                Dev Reprod
                DR
                Development & Reproduction
                The Korean Society of Developmental Biology
                2465-9525
                2465-9541
                September 2017
                30 September 2017
                : 21
                : 3
                : 307-315
                Affiliations
                [1 ] Department of Life Science, Sangmyung University, Seoul 03016, Korea
                Author notes
                []Corresponding Author : Sung-Ho Lee, Ph.D., Department of Life Science, Sangmyung University, Hongjmoon-2 gil 20, Jongrho-Gu, Seoul 03016, Republic of Korea. Tel: +82-2-2287-5139, Fax: +82-2-2287-0070, E-mail: shlee@ 123456smu.ac.kr
                Article
                dr-21-3-307
                10.12717/DR.2017.21.3.307
                5651697
                121f64ec-606c-4dc3-86cc-80f5be4bdab9
                ⓒ Copyright 2017 The Korean Society of Developmental Biology

                This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 September 2017
                : 20 September 2017
                : 22 September 2017
                Funding
                Funded by: CrossRef http://dx.doi.org/10.13039/501100002645, Sangmyung University;
                Categories
                Original Research Paper
                Custom metadata
                2017-09-30

                orchidectomy (orx),chemical castration,hypertonic saline,bilateral intratesticular injection(biti),rat

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