수컷 흰쥐 뇌하수체의 생식소자극호르몬 발현에 미치는 Ethane 1,2-Dimethane Sulfonate(EDS)의 효과
Effect of Ethane 1,2-Dimethane sulfonate(EDS) on the Expression of Pituitary Gonadotropin in Male Rats
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Ethane 1,2-dimethane sulfonate(EDS)은 Leydig cells(LC)만을 선별적 사멸을 유도하는 약물로서 가역적인 테스토스테론(testosterone, T) 결핍 흰쥐 모델을 만드는데 널리 사용된다. 본 연구에서는 수컷 흰쥐 뇌하수체의 생식소자극호르몬인 LH와 FSH의 발현에 미치는 EDS 투여 효과를 조사하였다. 성숙한 수컷 흰쥐(SD strain, 300-350 g B.W.)에 EDS(75 mg/kg, i.p.)를 1회 복강주사하고 주사 후 0, 1, 2, 3, 4, 5, 6 그리고 7주가 경과한 날 희생시켰다. 뇌하수체로부터 total RNA를 추출한 후 뇌하수체 glycoprotein hormone common alpha subunit(Cα), LH beta subunit(LHβ), FSH beta subunit(FSHβ) 그리고 GnRH 수용체(GnRH-R)의 발현 변화를 semi-quantitative RT-PCR로 측정하였다. 그 결과, Cα 전사수준은 주사 후 1주부터 급격히 상승하여 주사 후 4주까지 유의하게 높게 유지되다가 5주 후부터 control 수준으로 회귀하였다. LHβ 전사 수준은 주사 후 2주부터 유의하게 상승하여 주사 후 4주에 최고 수준에 도달하였으며, 5주 후부터 control 수준으로 감소하였다. FSHβ 전사수준은 주사 후 2주부터 유의하게 상승하여 주사 후 3주에 최고 수준에 도달하였으며, 4주 후부터 감소하여 5주후에 최소치를 보였다. 유사하게, GnRH-R 전사수준도 주사 후 2주부터 유의하게 상승하여 주사 후 3주에 최고 수준에 도달하였으며, 5주후부터 control 수준으로 감소하였다. 본 연구는 EDS 주사에 의해 수컷 흰쥐 뇌하수체 전엽에서의 생식소자극호르몬 subunit들과 GnRH-R의 발현 변화가 가역적으로 유도될 수 있음을 보여준 것이다. EDS 주사 모델은 수컷 흰쥐에서의 시상하부-뇌하수체 신경내분비 축의 호르몬 조절에 대한 기작을 이해하는데 도움이 될 것이다.
Abstract
Ethane 1,2-dimethane sulfonate(EDS), a toxin which specifically kills Leydig cells(LC), has been widely used to prepare the reversible testosterone(T) depletion rat model. In the present study, we monitored the gene expression profiles of pituitary gonadotropins, LH and FSH, up to 7 weeks after EDS injection. Adult male Sprague-Dawley rats(300-350g B.W.) were injected with a single dose of EDS(75mg/kg i.p.) and sacrificed on weeks 0, 1, 2, 3, 4, 5, 6 and 7. Total RNAs were purified from each pituitary, and the message levels of common alpha subunit(Cα) of pituitary glycoprotein hormones, LH beta subunit(LHβ), FSH beta subunit(FSHβ) and GnRH receptor(GnRH-R) were evaluated by semi-quantitative RT-PCRs. The message levels of Cα increased sharply during weeks 1-4, then return to the control level on week 5. The mRNA levels of LHβ were elevated after week 2, reached the peak at week 4, then declined to the control level after week 5. The message levels of FSHβ were elevated after week 2, reached the peak at week 3, then declined to the nadir at week 5. Similarly, the mRNA levels of GnRH-R were elevated after week 2, reached the peak at week 3, then gradually declined to the control level after week 5. The present study indicated that EDS treatment could induce reversible alterations in the transcriptional activities of gonadotropin subunits and GnRH-R in the anterior pituitary from male rats. EDS injection model might be useful to understand the mechanism of hormonal regulation of hypothalamus-pituitary neuroendocrine axis in male rats.
참고문헌 (18)
- "step method of RNA isolation by acid guanidium thiocyanate", phe(l), pp.159~ (1987)
- "Androgen suppression of GnRH stimulated rat LHbeta gene transcription occurs through Sp1 sites in the distal GnRH", 15, pp.1906~1917 (2001)
- "Gonadal regulation of gonadotropin subunit gene expression evidence for regulation of follicle beta messenger ribonucleic acid by nonsteroidal hormones in female rats. Endocrinology 127", pp.806~ (1990)
- "Androgens and estrogens in their negative feedback action in the hypothalamo site of action and evidence of their interaction. J Steroid Biochem 33", pp.761~ (1989)
- "Effects of antiandrogens and ethane dimethane sulphonate bioactivity and secretion of pituitary gonadotrophins in male rats. Mol Cell Endocrinol 91", pp.125~ (1993), on gene expression
- "Testosterone differentially modulates gonadotropin subunit messenger ribonucleic acid responses to gonadotropin", pp.2883~ (1990)
- "Comparative protective actions of gonadotrophins and testosterone against the antispermatogenic action of ethane dimethanesulphonate. J Reprod Fertil 71", pp.401~ (1984)
- "Effect of ethane 1 on the testicular expression of steroidogenesis related genes and epididymal sperm count in the adult rat", 23, pp.17~23 (2005)
- "Expression of gonadotropin-releasing hormone (GnRH) receptor gene is altered by GnRH agonist desensitization in a manner similar to that of gonadotropin beta-subunit genes in normal and castrated rat pituitary", 136, pp.2803~2908 (1995)
- "Endocrinology of the hypothalamic testicular axis with particular reference to the hormonal control of spermatogenesis. Baillieres Clin Endocrinol Metab 1", pp.87~ (1987)
- "Gonadotropin subunit messenger RNA concentrations after blockade of gonadotropin subunit messenger RNA by posttranscriptional mechanisms. Mol Endocrinol 4" (1990), testosterone selectively increases follicle
- "role and secretion in the rat.Recent Prog Horm Res 46", pp.257~ (1990)
- "Molecular aspects of steroid hormone action in the male reproductive axis", 18, pp.341~344 (1997)
- "Effect of ethane 1,2-dimethane sulfonate(EDS) on the apoptosis in the rat epididymis", 10, pp.203~209 (2006)
- "Hormonal regulation of Leydig cell proliferation and differentiation in rodent testis: a dynamic interplay between gonadotrophins and testicular factors", 11, pp.507~518 (2005)
- "stimulating hormone and luteinizing hormone secretion in male rats orchidectomized or injected with ethylene dimethane sulfonate. Endocrinology 133", pp.1181~ (1993)
- "Effects of testosterone on gonadotropin subunit messenger ribonucleic acids in the presence or absence of gonadotropin", pp.734~ (1992)
- "Sex steroids and the control of LHRH secretion. J Steroid Biochem Mol Biol 40", pp.163~ (1991)