Some biological activities of cronolone and medroxyprogesterone acetate in the uterus of the sheep, mouse and rabbit

1989 ◽  
Vol 1 (2) ◽  
pp. 157 ◽  
Author(s):  
X Zhang ◽  
BG Miller
Keyword(s):  
Biological Activity ◽  
Medroxyprogesterone Acetate ◽  
Biological Activities ◽  
Decidual Cell ◽  
Cell Reaction ◽  
Limited Growth ◽  
Mouse Uterus ◽  
Breeding Activity ◽  
Ovariectomized Mice

Cronolone (9 alpha-fluoro-11 beta-hydroxy-17 alpha-acetoxypregn-4-ene-3,20-dione) is widely employed to regulate breeding activity in the ewe, but its biological activity in the uterus of this and most other species has not been studied. In this study several in vivo uterus-related activities of cronolone have been examined in the sheep, mouse and rabbit. In some experiments the corresponding activities of medroxyprogesterone acetate (6 alpha-methyl-17 alpha-acetoxypregn-4-ene-3,20-dione, MAP) were also examined. Cronolone maintained pregnancy in ovariectomized ewes but not in ovariectomized mice and rabbits; it terminated pregnancy in some mice and in all rabbits that were receiving daily progesterone treatment. Cronolone could not sensitize the mouse uterus for the induction of the decidual-cell reaction or block the induction of such sensitivity by progesterone, but did support limited growth of the oil-stimulated horn after sensitization with progesterone. Cronolone induced uteroglobin secretion by rabbit endometrium. It was concluded that, whereas MAP is a potent progestogen in the sheep, mouse and rabbit, cronolone is a progestogen in the sheep and rabbit only. In the mouse and especially the rabbit, cronolone has other, non-progestational activities, which block pregnancy.

ABSENCE OF OESTRADIOL-17β DEHYDROGENASE FROM THE PROGESTERONE-DOMINATED MOUSE UTERUS

1980 ◽  
Vol 85 (1) ◽  
pp. 155-159 ◽  
Author(s):  
B. F. CLARK
Keyword(s):  
Biological Activity ◽  
Water Soluble ◽  
Human Endometrium ◽  
Mouse Uterus ◽  
Uterine Lumen ◽  
Ovariectomized Mice ◽  
Metabolic Conversion

SUMMARY In the mouse uterus the development of sensitivity to a decidualizing stimulus requires large amounts of progesterone and small amounts of oestradiol-17β. During this process progesterone induces changes in the sensitivity of the tissues of the uterus to oestrogen. From observations of human endometrium it has been suggested that progesterone modulates the biological activity of oestradiol-17β by stimulating the metabolic conversion of oestradiol-17β to oestrone. Accordingly [6,7-3H]oestradiol-17β was injected subcutaneously into ovariectomized mice at various stages of the development of sensitivity to a decidualizing injection of oil into the uterine lumen. Radioactivity was extracted 4 h later, fractionated and identified. There was no alteration in the amounts of oestradiol, oestrone or water-soluble metabolites in the uteri whether the mice were treated with progesterone or with progesterone plus oestrogen or whether the uterine horns were decidualized for 24 or 48 h. The results suggest that in vivo the metabolism of oestradiol-17β by the uterus is not stimulated by progesterone.

scholarly journals Parallelism of Chemicostructural Properties between Filgrastim Originator and Three of Its Biosimilar Drugs

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Alessandra Gianoncelli ◽  
Michela Bertuzzi ◽  
Michela Guarienti ◽  
Sara Vezzoli ◽  
Sara Anna Bonini ◽  
...  
Keyword(s):  
Biological Activity ◽  
Reference Product ◽  
Biological Activities ◽  
Chemical Characterization ◽  
Structural Similarity ◽  
Functional Assay ◽  
Biological Drugs ◽  
Reference Drug ◽  
Rp Hplc

The approval and granting of marketing authorization for a putative biosimilar is based on strong comparability studies with its biological reference product. This is due to the complexity of the structure and nature of the manufacturing process of biological drugs. Hence, a rigorous analytical workflow for chemical characterization and clinical trials to evaluate the efficacy and safety is required to demonstrate their high similarities to the reference drug. This work is focused on the comparison of the originator of filgrastim with three of its biosimilars by evaluating their structural similarity and biological activity. Qualiquantitative analyses were performed by MALDI-TOF/TOF-MS and RP-HPLC-UV. An innovative functional assay using zebrafish as the animal model was developed to evaluate the biological activities of the drugs. The different analyses performed in this study highlighted the structural similarity of biosimilar drugs and their originator. This result was further confirmed by a similar in vivo biological activity.

scholarly journals Biological activities of recombinant chicken leptin C4S analog compared with unmodified leptins

2000 ◽  
Vol 279 (1) ◽  
pp. E116-E123 ◽  
Author(s):  
S. Dridi ◽  
N. Raver ◽  
E. E. Gussakovsky ◽  
M. Derouet ◽  
M. Picard ◽  
...  
Keyword(s):  
Biological Activity ◽  
Food Intake ◽  
Leptin Receptor ◽  
Biological Activities ◽  
Wild Type ◽  
Escherichia Coli Cells ◽  
Prokaryotic Expression Vector ◽  
Long Form

The chicken leptin sequence, in contrast to mammalian leptins, contains an unpaired Cys at position 3 of the original cDNA ( AF012727 ). The presence of an extra Cys may confer a different structure and affect the leptin's biological activity. To address this, we studied the effects of wild-type and mutated (C4S) chicken leptins in vitro and in vivo and compared them with mammalian leptin prepared from ovine leptin cDNA. The prokaryotic expression vector pMON, encoding full-size A(−1) chicken leptin ( AF012727 ), was mutated using a mutagenesis kit, yielding the C4S analog. Escherichia coli cells transformed with this vector overexpressed large amounts of chicken leptin C4S upon induction with nalidixic acid. The expressed protein, found in the inclusion bodies, was refolded and purified to homogeneity on a Q-Sepharose column, yielding three electrophoretically pure fractions, eluted from the column by 100, 125, and 150 mM NaCl, respectively. All three fractions showed a single band of the expected molecular mass (16 kDa) and were composed of >95% monomeric protein. Proper refolding was evidenced by comparing the circular dichroism spectrum of the analog with spectra of nonmutated chicken and ovine leptins. The biological activity of the C4S analog was evidenced by its ability to stimulate proliferation of leptin-sensitive BAF/3 cells transfected with a long form of human leptin receptor construct similar to its nonmutated counterpart, indicating that Cys4 plays no role in leptin activity. The in vitro activity of both wild-type and mutated chicken leptins was ∼10-fold lower than that of ovine leptin. After intravenous or intraperitoneal injections, C4S analog and the nonmutated chicken and ovine leptins all lowered the food intake of starved 9-day-old broiler or 5-wk-old layer male chickens by 11–34%. Monitoring food behavior revealed that the attenuated food intake resulted not from a decreased number of approaches to the feeders but from a decrease in the average time spent eating during each approach.

ENDOCRINE CONTROL OF ENDOMETRIAL SENSITIVITY DURING THE INDUCTION OF THE DECIDUAL CELL REACTION IN THE MOUSE

1966 ◽  
Vol 36 (3) ◽  
pp. 239-248 ◽  
Author(s):  
C. A. FINN
Keyword(s):  
Time Interval ◽  
Decidual Cell ◽  
Cell Reaction ◽  
Endocrine Control ◽  
Optimum Time ◽  
Ovariectomized Mice

SUMMARY The decidual cell reaction (DCR) of ovariectomized mice treated with hormones and stimulated by the intrauterine injection of oil was investigated to obtain information about the control of uterine sensitivity during implantation. Three factors were studied; oestrogen given at the time of oestrus, progesterone and oestrogen given at the time of the nidatory surge. For the induction of the DCR by oil both 'oestrous' oestrogen and 'nidatory surge' oestrogen were essential, whereas neither were necessary for the traumatic DCR. The quantity of nidatory surge oestrogen was very critical; 0·01 μg. were effective, 0·0625 μg. inhibitory. There was no quantitative interaction between nidatory surge oestrogen and progesterone, indicating that in this situation the two hormones are acting independently. The optimum time interval between initiating the oestrogen surge and injecting the oil was between 4 and 8 hr. No response was obtained when the oestrogen surge was produced and the stimulus applied on the second day of treatment with progesterone; maximal responses were obtained on the fourth and fifth day and a reduced response on the seventh day. After an oestrogen surge on the fourth day, it was not possible to elicit an oil DCR to a further dose of oestrogen on the fifth day, indicating that the period of sensitivity induced by the surge on the fourth day is followed by a period of refractoriness.

Progress and development of C-3, C-6, and N-9 position substituted carbazole integrated molecular hybrid molecules as potential anticancer agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Pratibha Mehta Luthra ◽  
Nitin Kumar
Keyword(s):  
Biological Activity ◽  
Side Effects ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Structural Motif ◽  
Hybrid Compounds ◽  
Hybrid Molecules ◽  
Anticancer Mechanism ◽  
Pharmacologically Active

Abstract: The carbazole skeleton, a key structural motif occurring naturally or chemically synthesized, have shown various biological activities. Molecular hybridization based on the combination of two or more bioactive pharmacophores has been an important tool to convert the potent structural leads to form new hybrid compounds with improved biological activity. In recent years, modifications/substitutions of the carbazole motif at C3, C6, N9 position have been carried to develop novel carbazole based potential anticancer agents in the cancer therapy. In the last fifteen years, several compounds based on carbazole core integrated to pharmacologically active molecular hybrid having active pharmacophore such as 1,3,4-thiadiazole, thiazole, guanidine, sulfonamides, glyoxamides, imidazole, phenanthrene, rhodamine, chalcones, imidazopyridine, platinum 2H-chromen-2-one, hydrazones, piperazine, Isoxazole-thiadiazole, pyrazole etc. have been synthesized showing anticancer profile at sub-micromolar to nano-molar concentrations. We have thoroughly reviewed the design, progress and development of C-3, C-6, and N-9 position substituted carbazole derivatives integrated with various medicinally active pharmacophore as potential anticancer agents evaluated against various cancer cell lines. Additionally, the anticancer mechanism and in vivo activity of the reported compounds have been discussed. This study will support in designing of a new pharmacophore that can be linked to carbazole motif for development for new, potent and target specific anticancer drugs with improved pharmacokinetics and minimal side effects.

scholarly journals The Decidual Cell Reaction in the Mouse Uterus: DNA Synthesis and Autoradiographic Analysis of Responsive Cells

1978 ◽  
Vol 18 (3) ◽  
pp. 506-509 ◽  
Author(s):  
Barry E. Ledford ◽  
Judith C. Rankin ◽  
Veronica L. Froble ◽  
Martin J. Serra ◽  
Roger R. Markwald ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Decidual Cell ◽  
Cell Reaction ◽  
Mouse Uterus ◽  
Autoradiographic Analysis

scholarly journals LEFTY, a Member of the Transforming Growth Factor-β Superfamily, Inhibits Uterine Stromal Cell Differentiation: A Novel Autocrine Role

Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 1320-1330 ◽  
Author(s):  
Meiyi Tang ◽  
Devendra Naidu ◽  
Patrick Hearing ◽  
Stuart Handwerger ◽  
Siamak Tabibzadeh
Keyword(s):  
Medroxyprogesterone Acetate ◽  
Transforming Growth Factor ◽  
Marker Genes ◽  
Specific Marker ◽  
Normal Endometrium ◽  
Ovariectomized Mice ◽  
Decidual Cells ◽  
Pregnant Mice

LEFTY is expressed in normal endometrium in cells that decidualize. To understand the importance of this expression, we have studied the effect of LEFTY on decidualization in vitro and in vivo. Exposure of human uterine fibroblast (HuF) cells to recombinant LEFTY blocked the induction of the decidual differentiation-specific marker genes, IGFBP1 (IGF-binding protein 1) and PRL (prolactin) in response to medroxyprogesterone acetate, estradiol, and prostaglandin E2. The inhibitory effect was associated with decreased induction of the transcription factors ETS1 and FOXO1, both of which are essential for decidualization. Overexpression of LEFTY in decidualized HuF cells with an adenovirus that transduced LEFTY caused a marked decrease in IGFBP1 secretion, and withdrawal of medroxyprogesterone acetate from decidualized cells resulted in a decrease in IGFBP1 secretion and an increase in LEFTY expression. Moreover, overexpression of LEFTY in decidualized cells reprogrammed the cells to a less differentiated state and attenuated expression of decidual markers. Uterine decidualization was markedly attenuated and litter size was significantly reduced by retroviral transduction of LEFTY in the uterine horns of pregnant mice or by induction of LEFTY expression by doxycycline treatment in Tet-On conditional LEFTY transgenic pregnant mice. In addition, administration of the contraceptive agent drospirenone to ovariectomized mice induced a marked increase in LEFTY expression and inhibited decidualization. Taken together, these finding indicate that LEFTY acts as a molecular switch that modulates both the induction of decidual differentiation and the maintenance of a decidualized state. Because decidual cells express abundant amounts of LEFTY, the action of LEFTY on decidualization occurs by an autocrine mechanism.

scholarly journals Peptide fragments of bradykinin show unexpected biological activity not mediated by B1 or B2 receptors

2021 ◽  
Author(s):  
Igor Souza-Silva ◽  
Cristiane de Paula ◽  
Lucas Bolais-Ramos ◽  
Anderson Santos ◽  
Filipe da Silva ◽  
...  
Keyword(s):  
Biological Activity ◽  
Adult Male ◽  
Wistar Rats ◽  
Vascular Reactivity ◽  
Biological Activities ◽  
No Production ◽  
Peptide Fragments ◽  
Kinin System ◽  
Male Wistar Rats

Background and purpose: Bradykinin [BK-(1-9)] is an endogenous nonapeptide involved in multiple physiological and pathological processes. A long-held belief is that peptide fragments of BK-(1-9) are biologically inactive. Here, we have tested the biological activities of BK-(1-9) and two major peptide fragments in human and animal systems. Experimental Approach: Levels of BK peptides in male Wistar rat plasma were quantified by mass spectrometric methods. Nitric oxide was quantified in human, mouse and rat cells, and loaded with DAF-FM. We used aortic rings from adult male Wistar rats to test vascular reactivity. Changes in blood pressure and heart rate were measured in conscious adult male Wistar rats. Key results: Plasma levels of BK-(1-7) and BK-(1-5) in rats were increased following infusion of BK-(1-9). All tested peptides induced NO production in all cell types tested. However, unlike BK-(1-9), NO production elicited by BK-(1-7) or BK-(1-5) was not inhibited by B or B receptor antagonists. BK-(1-7) or BK-(1-5) also induced concentration-dependent vasorelaxation of aortic rings, without involving B or B receptors. In vivo, either intravenous or intra-arterial administration of BK-(1-7) or BK-(1-5) induced similar hypotension response. Conclusions and implications: BK-(1-7) and BK-(1-5) are endogenous peptides present in plasma. They are formed, at least partially, through the BK-(1-9) proteolysis. BK-related peptide fragments show biological activity, not mediated by B or B receptors. These BK-fragments could constitute new, active components of the kallikrein-kinin system.

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