Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Keishi-bukuryo-gan (TJ-25) is a traditional Chinese herbal remedy containing five components: bark of Cinnamomum cassia, root of Paeonia lactiflora, seed of Prunus persica or P. persiba var. davidiana, carpophores of Poria cocos and root bark of Paeonia suffruticosa. This preparation has been used in the treatment of gynecological disorders such as hypermenorrhea, dysmenorrhea and infertility. In the present study, the effects of TJ-25 on plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol (E2), and on uterine wet weight and thymidine kinase (TK) activity were documented in immature rats. Long-term daily oral administration of TJ-25 (300 mg/kg) for 14 days decreased plasma levels of LH, FSH and E2 by 94%, 67% and 50%, respectively, compared to controls. Uterine wet weight and TK activity were reduced to 65% and 64% that of controls, respectively. Short-term effects of TJ-25 on E2 were also examined. Thirty hours after administration of E2 (1.0 micrograms/kg) alone, uterine wet weight and TK activity were elevated 2.4- and 21-fold, respectively, over controls. However, simultaneous administration of TJ-25 (three consecutive doses, every 12 h) with E2 reduced E2-induced increases in uterine wet weight and TK activity by 29% and 39%, respectively. Treatment with TJ-25 also enhanced LH-RH-induced increases in plasma LH and FSH levels 1.2- and 2.5-fold, respectively, as compared with controls. The results obtained in the present study indicate that TJ-25 may act as a LH-RH antagonist and/or as a weak anti-estrogen.
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PMID:Effects of a Chinese herbal medicine, keishi-bukuryo-gan, on the gonadal system of rats. 314 30

Suppression of gonadotropins was induced by gancyclovir or acyclovir treatment in transgenic mice carrying 2.3 kb of bovine follicle-stimulating hormone beta (FSH beta) promoter fused to Herpes simplex virus thymidine kinase (tk) coding sequence. Transgenic tk and endogenous FSH beta were immunohistochemically co-localized in the same pituitary cells. In adult castrated transgenic males, gancyclovir treatment reduced plasma FSH (30%, P < 0.001). In intact juvenile gancyclovir treated mice, the reduction of pituitary FSH, and in males also of plasma FSH, was greater (50-70%, P < 0.05-0.01). A concomitant suppression of luteinizing hormone (LH) (50%, P < 0.01) was observed in female pups. The most pronounced reduction of gonadotropins was observed in newborn transgenic pups treated in utero with acyclovir. Both males and females had significantly lower pituitary levels of FSH (75-55%), LH (80-90%) or both (P < 0.05-0.01). Less pronounced decreases (30-40%, P < 0.01) were observed in plasma FSH. No apparent defects were seen in the testes of the transgenic, acyclovir treated, newborn pups. This mouse model is applied to study the dynamics of the gonadotropes and the role of gonadotropins in the maturation of the reproductive functions.
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PMID:Induced ablation of gonadotropins in transgenic mice expressing herpes simplex virus thymidine kinase under the FSH beta-subunit promoter. 775 21

The bovine FSH beta-subunit promoter (2.3 kb) was coupled to the coding sequence of the Herpes simplex virus type 1 thymidine kinase (HSV-tk) gene and introduced into mouse embryos. A full-length tk transcript was found in the pituitary and testis. In the testis an additional truncated version of tk mRNA was also expressed. Two sets of primer extension fragments were identified, one corresponding to transcription initiation at or near the cap site of the FSH-beta gene, the other to transcription initiation within the tk gene. Furthermore, the latter, shorter transcript contained a 227 bp deletion. Only the long transcript was translated into immunoreactive tk in the later stages of developing spermatids. The tk protein was also functional in the testes, since spermatogenesis was either arrested or the germinal epithelium almost completely destroyed in transgenic males treated with the antiherpetic agent. If the FSH-beta-HSV-tk transgene also functions correspondingly in the pituitary, these mice will provide a useful model for studies on FSH.
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PMID:The FSH beta-subunit promoter directs the expression of Herpes simplex virus type 1 thymidine kinase to the testis of transgenic mice. 827 35

The ovarian expression of the endogenous follicle-stimulating hormone beta-subunit (FSH beta) and common alpha-subunit (C alpha) genes, and a herpes simplex virus thymidine kinase (tk) transgene, driven by a 2.3 kb bovine FSH beta promoter, was studied in normal and transgenic (tg) mice, tk functions not only as a neutral reporter that enables the study of the promoter function but also as an exogenously inducible toxigene. Reverse transcription-PCR followed by Southern blot hybridization with a nested probe was used to show the expression of the gene at the mRNA level. Common alpha-subunit mRNA was detected in the pituitary gland and ovaries of normal adult mice. We have previously detected endogenous FSH beta and tg tk mRNAs in the mouse pituitary, testis and ovary. In this study, the cellular localization of the corresponding proteins was visualized by immunocytochemistry. In normal mouse ovaries a positive reaction with FSH beta and C alpha antisera was seen in some of the corpora lutea and most prominently in the interstitial cells. A positive reaction with the tk antiserum was seen in the same cell types of tg mouse ovaries, but not in those of non-tg mice. Cell-ablation-inducing treatment (gancyclovir, 20 mg/kg per day, for 14 days) of tg female mice reduced pituitary FSH concentrations by 52% (P < 0.05) but did not affect pituitary LH or plasma gonadotropins compared with non-tg females treated in the same way. A longer period of cell ablation induction (acyclovir 400 mg/kg per day, for 21 days) reduced not only pituitary but also plasma FSH concentrations (55 and 57% respectively; P < 0.05) without affecting LH. This treatment also reduced ovarian weight by 38% (P < 0.01). In conclusion, our results show first that the endogenous FSH beta and C alpha proteins are produced in the mouse ovary. Hence, endogenously synthesized FSH or its subunits may have a role in the paracrine regulation of ovarian function. Secondly, the FSH beta promoter directs the expression of tg tk in the pituitary gonadotrope cells, as shown by specific but partial ablation of FSH-producing cells after induction by gancyclovir and acyclovir. In the ovary, tk protein was localized to the same compartments as the endogenous gonadotropin subunit proteins. This further confirms our finding of ovarian expression of the FSH subunit genes.
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PMID:Pituitary and ovarian expression of the endogenous follicle-stimulating hormone (FSH) subunit genes and an FSH beta-subunit promoter-driven herpes simplex virus thymidine kinase gene in transgenic mice; specific partial ablation of FSH-producing cells by antiherpes treatment. 886 93