Endometriosis is determined by genetic factors, and the prevalence of genetic polymorphisms varies greatly depending on the ethnic group studied. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of 9 genes involved in estrogen biosynthesis and metabolism and the risks of endometriosis. Three hundred patients with endometriosis and 337 non-endometriotic controls were recruited. Thirty four non-synonymous SNPs, which change amino acid residues, were analyzed using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). The functions of SNP-resulted amino acid changes were analyzed using multiple web-accessible databases and phosphorylation predicting algorithms. Among the 34 NCBI-listed SNPs, 22 did not exhibit polymorphism in this study of more than 600 Taiwanese Chinese women. However, homozygous and heterozygous mutants of 4 SNPs - rs6165 (genotype GG+GA, 307Ala/Ala+307Ala/Thr) of FSHR, rs 6166 (genotype GG+GA, 680Ser/Asn+680Ser/Ser) of FSHR, rs2066479 (genotype AA+AG, 289Ser/Ser+289Ser/Gly) of HSD17B3 and rs700519 (genotype TT+TC, 264Cys/Cys+264Cys/Arg) of CYP19, alone or in combination, were significantly associated with decreased risks of endometriosis. Bioinformatics results identified 307Thr of FSHR to be a site for O-linked glycosylation, 680Ser of FSHR a phosphorylated site by protein kinase B, and 289Ser of HSD17B3 a phosphorylated site by protein kinase B or ribosomal protein S6 kinase 1. Results of this study suggest that non-synonymous polymorphisms of FSHR, HSD17B3 and CYP19 genes may modulate the risk of endometriosis in Taiwanese Chinese women. Identification of the endometrosis-preferential non-synonymous SNPs and the conformational changes in those proteins may pave the way for the development of more disease-specific drugs.
JYL. The facilitatory effect of N-methyl-D-aspartate on sexual receptivity in female rats through GnRH release. Acta Endocrinol 1993;128:385-8. ISSN 0001-5598 The purpose of this study was to examine whether N-methyl-D-aspartate affects the sexual receptivity of female rats. Monosodium L-glutamate was used as a neurotoxin to induce hypogonadal status. Matured normal and monosodium L-glutamate-treated rats were ovariectomized and implanted subcutaneously with estradiol capsules. One week later, lordosis responsiveness was observed before and 10 min after N-methyl-D-aspartate (40 mg/kg of BW, ip) administration. The results showed that N-methyl-D-aspartate caused a remarkable increase of lordosis quotient in control rats but not in monosodium L-glutamate-treated rats. Moreover, the possible action site of N-methyl-D-aspartate in the enhancement of receptivity was evaluated by the post-castrational LH rise, pituitary LH release in response to GnRH, and N-methyl-D-aspartate-evoked GnRH releasability. The results revealed that: (a) serum levels of LH in monosodium L-glutamate-treated rats were lower (p <0.01) than those of control rats after ovariectomy; (b) there was no significant difference of pituitary LH release responsiveness to GnRH test between two groups; and (c) N-methyl-D-aspartate-evoked LH release in monosodium Lglutamate-treated rats was similar to that in the control rats. In conclusion, N-methyl-D-aspartate may facilitate the sexual receptivity through stimulating GnRH release. The failure of N-methyl-D-aspartate in enhancing receptivity in monosodium L-glutamate-treated rats is probably due to the cellular damage by monosodium L-glutamate on specific areas responsible for lordosis. Jau-NanLee, Department of Obstetrics and Ggnecologg, Kaohsiung Medical College, Kaohsiung, Taiwan, R.O.C. N-methyl-D-aspartate is a potent agonist of excitatory amino acid in neurotransmission (1-2). Excitatory amino acid has been known to induce LH secretion through stimulating GnRH release at the hypothalamic level (3-8), specifically acting at the preoptic area (9-11), where GnRH gene expression has been detected (12). GnRH can also facilitate lordosis behavior in female rats (13,14). It has been reported that the lordosis response in female rats was inhibited by the decrease of excitatory amino acid activity in the preoptic area (15).Our previous report demonstrated that treatment with monosodium L-glutamate (MSG) in the neonatal stage of female rat can result in suppression of circulating estrogen and progesterone levels as well as lordosis response in latter adult stage (16). Thus, neonatal MSG treatment in female rats was used in the present study as a model of hypogonadal status to investigate whether Nmethyl-D-aspartate facilitates the receptivity and to analyze the possible mechanism on the lordosis response. Materials and methodsAnimals and experiments Pregnant Long-Evans rats were caged individually. After birth, only female rats were selected. Some of them were injected with MSG (4 mg/g of BW, ip, Sigma Co...
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