암컷 마우스 생식기관의 형태에 미치는 에스트로겐 수용체 촉진제의 영향
Effects of Estrogen Receptor Agonist on Morphology in the Female Mouse Reproductive Organs
1
조회
0
다운로드
3
인용
0
참고문헌
초록
에스트로겐은 수컷과 암컷의 생식기관 내에서 구조적이고 기 능적인 변화를 유발하지만 그 정확한 기작에 대하여는 잘 알려 져 있지 않다. 에스트로겐의 기능과 연관지어, 본 연구에서는 암 컷 생식기관 내에서 에스트로겐 수용체 촉진제인 4,4′,4′′-(4- propyl-[1H]-pyrazole-1,3,5-triyl)tris phenol (PPT)의 작용을 확인 하고자 하였다. 성체 암컷 마우스에 castor oil 0.06 mL에 PPT 3 mg 농도로 희석한 용액을 1주일에 1회씩 3주, 5주, 8주 동안 각 각 피하주사 하였으며, 대조군에는 castor oil 0.06 mL만을 투여 하였다. 광학현미경을 이용하여 생식기관에 대한 PPT의 영향을 분석하였다. PPT에 의해 실험기간 동안 체중, 난소 및 지방조직 의 무게가 감소되었다. PPT 투여군에서는 대조군에 비해 난소의 직경이 감소되었으며, 난소 내 그라프여포와 황체의 수도 감소되 었다. 자궁의 경우, PPT에 의해 근육층과 내막층의 높이가 감소 함에 따라 내강이 증가되었다. 또한 자궁샘의 수도 감소되었다. 이런 결과들로 볼 때 PPT에 의해 암컷 생식기관의 형태학적 변 화가 유발되고 이로 인해 생식력에도 변화가 있을 것으로 보인 다.
Abstract
Estrogens induce pronounced structural and functional changes in male and female reproductive system, but the exact mechanisms of estrogen are not fully understood. In relation to estrogen’s function, the present study was designed to identify effects of estrogen receptor agonist, 4,4′,4′′- (4-propyl-[1H]-pyrazole-1,3,5-triyl)tris phenol (PPT) in the reproductive organ of the female mouse. The PPT was subcutaneously given to adult female mice at a weekly dosage of 3 mg in a volume 0.06 mL of vehicle for 3, 5 or 8 weeks whereas controls received weekly injections of the castor oil vehicle. Effects of PPT on reproductive organs were analyzed using a light microscope. PPT induced decreases of body, ovary and adipose tissue weights with experimental time. Ovary diameter of PPT treatment group was reduced as compared with control group. The number of Graffian follicle and corpus luteum was reduced in PPT treatment group. The luminal diameter of uterus was increased in relation with decrease of myometrium and endometrium height by PPT administration. The number of uterine glands was decreased by PPT treatment. These data indicate that PPT treatment induced morphological change of female reproductive organs resulting in alteration of fertility.
참고문헌 (35)
- Cho HW, "The antiestrogen ICI 182,780 induces early effects on the adult male mouse reproductive tract and long-term decreased fertility without testicular atrophy", Reprod Biol Endocrinol, 1, pp.57~ (2003)
- Cook JC, "Effects of dietary 17 beta-estradiol exposure on serum hormone concentrations and testicular parameters in male Crl : CD BR rats", Toxicol Sci, 44, pp.155~168 (1998)
- Couse JF, "Estrogen receptor null mice: What have we learned and where will they lead us", Endocrine Rev, 20, pp.358~417 (1999)
- Couse JF, "Characterization of the hypothalamic-pituitary-gonadal axis in estrogen receptor (ER) null mice reveals hypergonadism and endocrine sex reversal in females lacking ERα but not ERβ", Mol Endocrinol, 17, pp.1039~1053 (2003)
- Dahlman-Wright K, "International union of pharmacology. LXIV. Estrogen receptors", Pharmacol Rev, 58, pp.773~781 (2006)
- Dudley MW, "Activation of the human estrogen receptor by the antiestrogens ICI 182,780 and tamoxifen in yeast genetic systems: Implications for their mechanism of action", PNAS, 97, pp.3696~3701 (2000)
- Fritsch M, "A ligand-induced conformational change in the estrogen receptor is localized in the steroid binding domain", Biochem, 31, pp.5303~5311 (1992)
- Goyal HO, "Diethylstilbestrol-treated adult rats with altered epididymal sperm numbers and sperm motility parameters, but without alterations in sperm production and sperm morphology", Biol Reprod, 64, pp.927~934 (2001)
- Hall JM, "Analysis of the molecular mechanisms of human estrogen receptors alpha and beta reveals differential specificity in target promoter regulation by xenoestrogens", J Biol Chem, 277, pp.44455~44461 (2002)
- Heine PA, "Increased adipose tissue in male and female estrogen receptor-α knockout mice", PNAS, 97, pp.12729~12734 (2000)
- Hess RA, "Estrogen in the adult male reproductive tract", Reprod Biol Endocrinol, 1, pp.52~ (2003)
- Hess RA, "Morphologic changes in efferent ductules and epididymis in estrogen receptoralpha knockout mice", J Androl, 21, pp.107~127 (2000)
- Hess RA, "A role for oestrogens in the male reproductive system", Nature, 390, pp.509~512 (1997)
- Hong S, "Effects of GnRH agonist administered to mouse on apoptosis in ovary and production of estradiol and progesterone", Dev Reprod, 7, pp.49~56 (2003)
- Kraichely DM, "Conformational changes and coactivator recruitment by novel ligands for estrogen receptor-α and estrogen receptor-β: Correlations with biological character and distinct differences among SRC coactivator family members", Endocrinol, 141, pp.3534~3545 (2000)
- Kuiper G, "The novel estrogen receptor-beta subtype: Potential role in the cell- and promoter-specific actions of estrogens and antiestrogens", FEBS Lett, 410, pp.87~90 (1997)
- Kuiper G, "Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β", Endocrinol, 139, pp.4252~4263 (1998)
- Laudenslager ML, "Energy balance in ovariectomized rats with and without estrogen replacement", Am J Physiol, 238, pp.R400~405 (1980)
- Luconi M, "Genomic and nongenomic effects of estrogens: molecular mechanisms of action and clinical implications for male reproduction", J Steroid Biochem Mol Biol, 80, pp.369~381 (2002)
- Mak HY, "Molecular determinants of the estrogen receptor-coactivator interface", Mol Cell Biol, 19, pp.3895~3903 (1999)
- Mosselman S, "ER beta: Identification and characterization of a novel human estrogen receptor", FEBS Lett, 329, pp.49~53 (1996)
- Muramatsu M, "Estrogen receptors: How do they control reproductive and nonreproductive functions?", Biochem Biophys Res Commun, 270, pp.1~10 (2000)
- Murdoch FE, "The role of ligand in estrogen receptor regulation of gene expression", Mol Cell Endocrinol, 78, pp.C103~108 (1991)
- Nakamura T, "Estrogen receptor subtypes selectively mediate female mouse reproductive abnormalities induced by neonatal exposure to estrogenic chemicals", Toxicol, 253, pp.117~124 (2008)
- Oliveira CA, "Infertility and testicular atrophy in the antiestrogen-treated adult male rat", Biol Reprod, 65, pp.913~920 (2001)
- Oliveira CA, "The antiestrogen ICI 182,780 decreases the expression of estrogen receptor-alpha but has no effect on estrogen receptorbeta and androgen receptor in rat efferent ductules", Reprod Biol Endocrinol, 1, pp.75~ (2003)
- Onate SA, "Sequence and characterization of a coactivator for the steroid hormone receptor superfamily", Sci, 270, pp.1354~1357 (1995)
- Rosenfeld CS, "Gonadotropin induction of ovulation and corpus luteum formation in young estrogen receptor-α knockout mice", Biol Reprod, 62, pp.599~605 (2000)
- Schomberg DW, "Targeted disruption of the estrogen receptor-α gene in female mice: Characterization of ovarian responses and phenotype in the adult", Endocrinol, 140, pp.2733~2744 (1999)
- Senturk LM, "MCP-1 expression in human corpus luteum", Mol Hum Reprod, 5, pp.697~702 (1999)
- Shiau AK, "The structural basis of estrogen receptor", coactivator recognition and the antagonism of this interaction by tamoxifen, 1998, pp.95, 927~937
- Shimizu H, "Estrogen increases in vivo leptin production in rats and human subjects", J Endocrinol, 154, pp.285~292 (1997)
- Simoncini T, "Genomic and non-genomic effects of estrogens on endothe- lial cells", Steroids, 669, pp.537~543 (2004)
- Stauffer SR, "Pyrazole ligands: Structure-affinity", activity relationships and estrogen receptor-α-selective agonists, 2000, pp.43, 4934~4947
- Wade GN, "Tamoxifen mimics the effect of estradiol on food intake, body weight, and body composition in rats", Am J Physiol, 264, pp.R1219~1223 (1993)