The Influence of 17-Oxo- and 17-Hydroxy-16,17-secoestratriene Derivatives on Estrogen Receptor

2006 ◽  
Vol 71 (4) ◽  
pp. 532-542 ◽  
Author(s):  
Suzana Jovanović-Šanta ◽  
Julijana Petrović ◽  
Marija Sakač ◽  
Zorica Žakula ◽  
Esma Isenović ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
Estrogenic Activity ◽  
Total Loss ◽  
The Other ◽  
Binding Parameters ◽  
Antiestrogenic Activity ◽  
Other Hand

Since many of newly synthesised D-secoestratriene derivatives showed antiestrogenic effect, with almost a total loss of estrogenic activity, we studied the effects of some of these compounds on estrogen receptors (ER), the translocation of the estrogen-ER complexes formed in presence of competing substances into the nucleus, as well as the binding of these complexes to DNA. The results of uterotrophic effects of analysed derivatives are in agreement with the influence of these compounds on activity and binding parameters of estrogen receptors. Namely, compounds that show relatively high antiestrogenic activity predominantly increase Kd and inhibit translocation to nuclei of radioactive complexes formed in their presence. On the other hand, compounds that do not significantly change binding parameters of estrogen receptors do not show antiestrogenic effect in in vivo experiments.

scholarly journals Systemic and Cerebral Kinetics of 16α[18F]Fluoro-17β-Estradiol: A Ligand for the in vivo Assessment of Estrogen Receptor Binding Parameters

1995 ◽  
Vol 15 (2) ◽  
pp. 301-311 ◽  
Author(s):  
R. M. Moresco ◽  
R. Casati ◽  
G. Lucignani ◽  
A. Carpinelli ◽  
K. Schmidt ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
Receptor Binding ◽  
Time Course ◽  
Binding Parameters ◽  
Brain Areas ◽  
Estrogen Receptor Binding ◽  
17Β Estradiol ◽  
In Vivo Assessment

Estrogen receptors are expressed in several brain areas of various animal species, and steroid hormones exert physiologic and biochemical effects on the central nervous system. The aim of the present study was to evaluate in female adult rats, the suitability of 16α[18F]fluoro-17β-estradiol ([18F]FES), a selective estrogen receptor ligand, for the in vivo assessment of brain estrogen receptors. This was considered to be a preliminary step in evaluating the potential usefulness of [18F]FES for studies of cerebral estrogen receptors with positron emission tomography (PET) in nonhuman primates and human subjects. We evaluated (a) the time course of the metabolic degradation of [18F]FES in blood; (b) the time course of distribution of the tracer in discrete cerebral areas; (c) the inhibitory effect of increasing doses of cold estradiol on cerebral [18F]FES uptake; and (d) the possibility of in vivo quantification of estrogen receptor binding parameters using both equilibrium and dynamic kinetic analyses. We quantified [18F]FES binding to estrogen receptors using both equilibrium and dynamic kinetic analyses. The results of this study indicate that [18F]FES is a suitable tracer for the measurement of estrogen receptors in the pituitary and hypothalamus, using either the equilibrium or the kinetic analysis. However, [18F]FES is inadequate for the in vivo investigation of estrogen binding sites in brain areas with low receptor density, such as the hippocampus.

Oxytocin analogues with non-coded amino acid residues in position 8: [8-Neopentylglycine]oxytocin and [8-cycloleucine]oxytocin

1987 ◽  
Vol 52 (9) ◽  
pp. 2317-2325 ◽  
Author(s):  
Jan Hlaváček ◽  
Jan Pospíšek ◽  
Jiřina Slaninová ◽  
Walter Y. Chan ◽  
Victor J. Hruby
Keyword(s):  
Amino Acid ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
The Other ◽  
Amino Acid Residues ◽  
Phase Synthesis ◽  
Other Hand ◽  
Fragment Condensation

[8-Neopentylglycine]oxytocin (II) and [8-cycloleucine]oxytocin (III) were prepared by a combination of solid-phase synthesis and fragment condensation. Both analogues exhibited decreased uterotonic potency in vitro, each being about 15-30% that of oxytocin. Analogue II also displayed similarly decreased uterotonic potency in vivo and galactogogic potency. On the other hand, analogue III exhibited almost the same potency as oxytocin in the uterotonic assay in vivo and in the galactogogic assay.

In vitro insulin-mimetic activity and in vivo metallokinetic feature of oxovanadium(IV)porphyrin complexes in healthy rats

2012 ◽  
Vol 16 (01) ◽  
pp. 114-121 ◽  
Author(s):  
Tapan K. Saha ◽  
Yutaka Yoshikawa ◽  
Hirouki Yasui ◽  
Hiromu Sakurai
Keyword(s):  
The Other ◽  
Insulin Mimetic ◽  
Other Hand ◽  
Better Than

We prepared [meso-tetrakis(4-carboxylatophenyl)porphyrinato]oxovanadium(IV) tetrasodium, ([VO(tcpp)]Na4), and investigated its in vitro insulin-mimetic activity and in vivo metallokinetic feature in healthy rats. The results were compared with those of previously proposed insulin-mimetic oxovanadium(IV)porphyrin complexes and oxovanadium(IV) sulphate. The in vitro insulin-mimetic activity and bioavailability of [VO(tcpp)]Na4 were considerably better than those of [meso-tetrakis (1-methylpyridinium-4-yl)porphyrinato]oxovanadium(IV)(4+) tetraperchlorate ([VO(tmpyp)](ClO4)4) and oxovanadium(IV) sulphate. On the other hand, [VO(tcpp)]Na4 and [meso-tetrakis(4-sulfonatophenyl) porphyrinato]oxidovanadate(IV)(4-)([VO(tpps)]) showed very similar in vitro insulin-mimetic activity and in vivo metallokinetic feature in healthy rats. In particular, the order of in vitro insulin-mimetic activity of the complexes was determined to be: [VO(tcpp)]Na4 ≈ [VO(tpps)] > ([VO(tmpyp)](ClO4)4 > oxovanadium(IV) sulphate.

scholarly journals Seminal vesicle proteins SVS3 and SVS4 facilitate SVS2 effect on sperm capacitation

Reproduction ◽  
2016 ◽  
Vol 152 (4) ◽  
pp. 313-321 ◽  
Author(s):  
Naoya Araki ◽  
Natsuko Kawano ◽  
Woojin Kang ◽  
Kenji Miyado ◽  
Kaoru Yoshida ◽  
...  
Keyword(s):  
Seminal Vesicle ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
The Other ◽  
Sperm Capacitation ◽  
Other Hand ◽  
Sperm Membrane ◽  
Vesicle Secretion ◽  
Mammalian Spermatozoa

Mammalian spermatozoa acquire their fertilizing ability in the female reproductive tract (sperm capacitation). On the other hand, seminal vesicle secretion, which is a major component of seminal plasma, inhibits the initiation of sperm capacitation (capacitation inhibition) and reduces the fertility of the capacitated spermatozoa (decapacitation). There are seven major proteins involved in murine seminal vesicle secretion (SVS1-7), and we have previously shown that SVS2 acts as both a capacitation inhibitor and a decapacitation factor, and is indispensable forin vivofertilization. However, the effects of SVSs other than SVS2 on the sperm have not been elucidated. Since mouseSvs2–Svs6genes evolved by gene duplication belong to the same gene family, it is possible that SVSs other than SVS2 also have some effects on sperm capacitation. In this study, we examined the effects of SVS3 and SVS4 on sperm capacitation. Our results showed that both SVS3 and SVS4 are able to bind to spermatozoa, but SVS3 alone showed no effects on sperm capacitation. On the other hand, SVS4 acted as a capacitation inhibitor, although it did not show decapacitation abilities. Interestingly, SVS3 showed an affinity for SVS2 and it facilitated the effects of SVS2. Interaction of SVS2 and spermatozoa is mediated by the ganglioside GM1 in the sperm membrane; however, both SVS3 and SVS4 had weaker affinities for GM1 than SVS2. Therefore, we suggest that separate processes may cause capacitation inhibition and decapacitation, and SVS3 and SVS4 act on sperm capacitation cooperatively with SVS2.

Transcriptional activation of the estrogen receptor

1993 ◽  
Vol 39 (2) ◽  
pp. 341-345 ◽  
Author(s):  
L L Wei
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
Transcriptional Activation ◽  
Breast Cancer Cells ◽  
Wild Type ◽  
Resistant Phenotype ◽  
Estrogen Receptor Positive ◽  
Almost All

Abstract Almost all breast cancer tumors progress to a hormone-resistant state. Evidence is presented that the existence of mutant estrogen receptors may explain some hormone-resistant phenotypes. Breast tumor cells bearing a mutant receptor that is constitutively active and does not bind hormone would have unregulated cell growth and thus appear to be hormone-independent. Alternatively, breast cancer cells may contain estrogen receptors that are transcriptionally inactive but when co-expressed with wild-type receptors render normal estrogen receptors inactive. These cells would be considered estrogen receptor-positive but would be hormone-resistant. The hormone-resistant phenotype could be further complicated by the finding that other nonreceptor proteins may also modulate the transcriptional activity of estrogen receptors. These findings, if substantiated in vivo, could add to the complexity of the hormone-resistant phenotype. Different strategies of treatment will need to be developed to effectively treat the various subtypes of hormone-resistant breast tumors.

scholarly journals Responsiveness of endometrial genes Connexin26, Connexin43, C3 and clusterin to primary estrogen, selective estrogen receptor modulators, phyto- and xenoestrogens

2002 ◽  
Vol 29 (2) ◽  
pp. 239-249 ◽  
Author(s):  
S Heikaus ◽  
E Winterhager ◽  
O Traub ◽  
R Grummer
Keyword(s):  
Estrogen Receptor ◽  
Reproductive Tract ◽  
Polychlorinated Biphenyl ◽  
Estrogenic Activity ◽  
Selective Estrogen Receptor Modulators ◽  
Complement C3 ◽  
Estrogen Receptor Modulators ◽  
Industrial Compounds ◽  
Receptor Modulators

Phytohormones and chemical compounds revealing estrogenic effects are of increasing interest for their possible influence on the physiology of the reproductive tract. The gap junction connexin (Cx) genes Cx26 and Cx43, the plasma glycoprotein clusterin gene and the complement C3 gene are highly regulated by estrogen in rat endometrium. To test the value of these genes as markers for estrogenic responsiveness we analyzed the effects of estradiol, diethylstilbestrol, the selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen, the phytoestrogens genistein and daidzein, and the industrial compounds DDT (1,1,1-trichloro-2-(2-chlorophenyl)-2-(4-chlorophenyl) ethane) and polychlorinated biphenyl (PCB) on the transcription of these genes in rat endometrium in vivo. Enhancement of Cx26 and decrease of clusterin transcripts expression by estradiol was observed at 0.03 micro g/250 g body weight (BW), and induction of C3 expression was observed at 0.05 micro g/250 g BW. A comparable effect was obtained by a tenfold higher concentration of diethylstilbestrol. Tamoxifen had a regulatory effect on this set of genes at about a 300-fold higher concentration, while raloxifen revealed much weaker estrogenic activity. No effect on Cx43 transcripts was observed with any of the compounds at the concentrations used. An effect of genistein was observed only on Cx26 expression, while PCB decreased clusterin transcripts. These results show that Cx26, C3 and clusterin reveal a comparable sensitivity to estrogens and SERMs. With respect to the phytoestrogen genistein, however, Cx26 seems to be the most sensitive gene. The analysis of clusters of estrogen-sensitive endometrial genes could help to identify estrogenic substances, assess their potency, and elucidate their mechanism of action.

scholarly journals Interplay between MPIase, YidC, and PMF during Sec-independent insertion of membrane proteins

2021 ◽  
Vol 5 (1) ◽  
pp. e202101162
Author(s):  
Yuta Endo ◽  
Yuko Shimizu ◽  
Hanako Nishikawa ◽  
Katsuhiro Sawasato ◽  
Ken-ichi Nishiyama
Keyword(s):  
Membrane Proteins ◽  
Molecular Basis ◽  
Terminal Region ◽  
Integral Membrane Proteins ◽  
The Other ◽  
Other Hand ◽  
Model Protein

Integral membrane proteins with the N-out topology are inserted into membranes usually in YidC- and PMF-dependent manners. The molecular basis of the various dependencies on insertion factors is not fully understood. A model protein, Pf3-Lep, is inserted independently of both YidC and PMF, whereas the V15D mutant requires both YidC and PMF in vivo. We analyzed the mechanisms that determine the insertion factor dependency in vitro. Glycolipid MPIase was required for insertion of both proteins because MPIase depletion caused a significant defect in insertion. On the other hand, YidC depletion and PMF dissipation had no effects on Pf3-Lep insertion, whereas V15D insertion was reduced. We reconstituted (proteo)liposomes containing MPIase, YidC, and/or F0F1-ATPase. MPIase was essential for insertion of both proteins. YidC and PMF stimulated Pf3-Lep insertion as the synthesis level increased. V15D insertion was stimulated by both YidC and PMF irrespective of the synthesis level. These results indicate that charges in the N-terminal region and the synthesis level are the determinants of YidC and PMF dependencies with the interplay between MPIase, YidC, and PMF.

scholarly journals In vivo phosphorylation of regulatory light chain of myosin II during mitosis of cultured cells

1994 ◽  
Vol 124 (1) ◽  
pp. 129-137 ◽  
Author(s):  
Y Yamakita ◽  
S Yamashiro ◽  
F Matsumura
Keyword(s):  
Light Chain ◽  
Myosin Ii ◽  
Mitotic Arrest ◽  
Regulatory Light Chain ◽  
The Other ◽  
Other Hand ◽  
Mlc Phosphorylation ◽  
Phosphate Incorporation ◽  
Mitotic Cells

Phosphorylation of the regulatory light chain of myosin II (MLC) controls the contractility of actomyosin in nonmuscle and muscle cells. It has been reported that cdc2 phosphorylates MLC in vitro at Ser-1 or Ser-2 and Thr-9 which protein kinase C phosphorylates (Satterwhite, L. L., M. J. Lohka, K. L. Wilson, T. Y. Scherson, L. K. Cisek, J. L. Corden, and T. D. Pollard. 1992 J. Cell Biol. 118:595-605). We have examined in vivo phosphorylation of MLC during mitosis and after the release of mitotic arrest. Phosphate incorporation of MLC in mitotic cells is found to be 6-12 times greater than that in nonmitotic cells. Phosphopeptide maps have revealed that the MLC from mitotic cells is phosphorylated at Ser-1 and/or Ser-2 (Ser-1/2), but not at Thr-9. MLC is also phosphorylated to a much lesser extent at Ser-19 which myosin light chain kinase phosphorylates. On the other hand, MLC of nonmitotic cells is phosphorylated at Ser-19 but not at Ser-1/2. The extent of phosphate incorporation is doubled at 30 min after the release of mitotic arrest when some cells start cytokinesis. Phosphopeptide analyses have revealed that the phosphorylation at Ser-19 is increased 20 times, while the phosphorylation at Ser-1/2 is decreased by half. This high extent of MLC phosphorylation at Ser-19 is maintained for another 30 min and gradually decreased to near the level of interphase cells as cells complete spreading at 180 min. On the other hand, phosphorylation at Ser-1/2 is decreased to 18% at 60 min, and is practically undetectable at 180 min after the release of mitotic arrest. The stoichiometry of MLC phosphorylation has been determined by quantitation of phosphorylated and unphosphorylated forms of MLC separated on 2D gels. The molar ratio of phosphorylated MLC to total MLC is found to be 0.16 +/- 0.06 and 0.31 +/- 0.05 in interphase and mitotic cells, respectively. The ratio is increased to 0.49 +/- 0.05 at 30 min after the release of mitotic arrest. These results suggest that the change in the phosphorylation site from Ser-1/2 to Ser-19 plays an important role in signaling cytokinesis.

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