Ovarian inhibin content in immature female rats following hypophysectomy: control by exogenous gonadotrophins

1988 ◽  
Vol 119 (2) ◽  
pp. 185-189 ◽  
Author(s):  
R. S. Carson ◽  
J. W. McMaster
Keyword(s):  
Female Rats ◽  
Dependent Manner ◽  
Immature Female ◽  
Ovarian Weight ◽  
Antral Follicles ◽  
Specific Radioimmunoassay ◽  
Dose Dependent ◽  
Ovarian Inhibin

ABSTRACT The effect of exogenous ovine gonadotrophins on ovarian inhibin content in hypophysectomized immature female rats was studied to determine which of the pituitary gonadotrophins control ovarian inhibin production in vivo. Inhibin and steroid contents of 27 000 g ovarian supernatants were measured by specific radioimmunoassay. Whereas injection of ovine (o)FSH resulted in dose-dependent increases in ovarian weight, progesterone and oestradiol content above that of control animals injected with diethylstilbestrol alone, injection of oLH was without significant effect. Similarly, ovarian inhibin content was not altered significantly by injection of oLH, but was increased in a dose-dependent manner by injection of oFSH. Concentrations of inhibin in serum were correlated directly with ovarian inhibin content. The results of this study indicate that ovarian inhibin content is increased by injection of oFSH but not oLH. It is likely, therefore, that inhibin production by small antral follicles is controlled by FSH activity alone. J. Endocr. (1988) 119, 185–189

Anti-idiotypic antibody as an oestrogen mimetic: removal of Fc fragment converts agonist to antagonist

1995 ◽  
Vol 145 (3) ◽  
pp. 409-416 ◽  
Author(s):  
D Sömjen ◽  
Y Amir-Zaltsman ◽  
B Gayer ◽  
G Mor ◽  
N Jaccard ◽  
...  
Keyword(s):  
Physiological Responses ◽  
Female Rats ◽  
Dependent Manner ◽  
Immature Female ◽  
Antibody Molecule ◽  
Cartilage Cells ◽  
Dose Dependent ◽  
Idiotypic Antibody

Abstract Previous studies indicated that the anti-idiotypic antibody (clone 1D5) caused an increase in uterine creatine kinase (CK) activity when administered in vivo to immature female rats, indicating that the antibody has oestrogenic-like activity. It was, therefore, of interest to investigate the structural requirements of clone 1D5 to act as an oestrogen mimetic in an in vitro model system. In the present study, the effect of clone 1D5 and its proteolytic fragments, F(ab′)2, Fab′ and Fc on CK activity was examined in cultured skeletal cells having functional oestrogen receptor (ER). Incubation of female-derived calvaria cells or epiphyseal cartilage cells with clone 1D5 (8·33 nm) or oestradiol (E2) (30 nm) for 24 h caused a significant increase in CK activity, indicating that clone 1D5 acted as an agonist. On the other hand, incubation of male-derived calvaria cells devoid of a functional ER with clone 1D5 or E2 did not have any effect on CK activity. Incubation of female-derived calvaria cells with clone 1D5 and E2 did not result in any further increase in CK activity, whereas dihydrotestosterone (DHT) did not alter the response to clone 1D5. The CK response to clone 1D5, in female-derived calvaria cells was time- and dose-dependent and could be inhibited in a dose-dependent manner by the oestrogen antagonist tamoxifen. In contrast, the proteolytic fragments of clone 1D5, the F(ab′)2 dimer (12 nm) and the Fab′ monomer (24 nm), and the Fc fragment (28 nm) did not have E2-like activity in these cells. However, while the Fab′ monomer or the Fc fragment, as well as clone 1D5, did not affect the response of the female-derived calvaria cells to E2, the F(ab′)2 dimer acted like an antagonist and completely inhibited the stimulatory effect of E2 or 1D5, but was unable to block the stimulatory effect of DHT on CK in male-derived calvaria cells. Collectively, these results imply that a bivalent antibody is necessary for the observed physiological responses, and that the anti-idiotypic antibody can be converted from an agonist to an antagonist by removal of the Fc portion of the antibody molecule. Furthermore, the anti-idiotypic antibody has an oestrogenic-like effect inhibited by tamoxifen only in skeletal cells capable of responding to E2. Journal of Endocrinology (1995) 145, 409–416

242 POTENTIAL ESTROGENIC EFFECT(S) OF PARABENS AT THE NEONATAL STAGE OF AN IMMATURE FEMALE RAT MODEL

2010 ◽  
Vol 22 (1) ◽  
pp. 279
Author(s):  
S. H. Hyun ◽  
E. B. Jeung
Keyword(s):  
Body Weight ◽  
Rat Model ◽  
Estrogenic Activity ◽  
Female Rats ◽  
Female Rat ◽  
Dependent Manner ◽  
Methyl Ethyl ◽  
Immature Female ◽  
Immature Rats ◽  
Dose Dependent

In this study, to examine the estrogenic activity effects of parabens on hormonal responsiveness and on change in the morphology of reproductive target tissues during a critical development stage in female rats, analyses for parabens including methyl-, ethyl-, propyl-, isopropyl-, butyl-, and isobutylparaben were performed in an immature female Sprague-Dawley rat model. Two hundred female immature rats (n = 10/group) were orally treated with these parabens from postnatal day 21 to 40 in a dose-dependent manner based on our previous study [62.5, 250, and 1000 mg/kg of body weight (BW) per day]. 17α-ethinylestradiol (EE;1 mg/kg of BWper day) was used as a positive control and corn oil as a vehicle.A high doseofmethyl- and isopropylparaben (1000 mg/kg of BW per day) resulted in a significant delay in the date of vaginal opening and a decrease in length of the estrous cycle (P < 0.05). In measurements of organ weight and body weight, we observed significant weight changes in ovaries, adrenal glands, thyroid glands, liver, and kidneys(P < 0.05); conversely, body weight was not altered following paraben treatment. In all groups exposedto paraben treatment, histological analysis of the ovaries from the immature rats revealed interstitial cell disorders, a lack of corpora lutea, an increase in the number of cystic follicles, and thinning of the follicular epithelium, which occurred in a dose-dependent manner. In addition, morphological studies of the uterus revealed the myometrial dysplasia suchas myometrial hyperplasia inthe high-doseofpropyl- and isopropylparaben (1000 mg/kgof BWper day) group and in all dose of butyl- and isobutylparabens groups. We also observed a significant decrease in serum estradiol and T4 concentrations in methyl-, ethyl-, propyl-, isopropyl-, and isobutylparaben-treated groups (P < 0.01 and 0.05).A receptor-binding assay indicated that the relative binding affini- ties of parabens to estrogen receptors occurred in the order: isobutylparaben > butylparaben > isopropylparaben = propylparaben > ethylparaben. These values were much less than the binding affinity for 17?-estradiol. Taken together, long-term exposure to parabens, which show less estrogenic activity than EEl, can produce suppressive effects on hormonal responsiveness and can disrupt the morphology of reproductive target tissues during this critical stage of development in immature female rats.

Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

1996 ◽  
Vol 76 (01) ◽  
pp. 111-117 ◽  
Author(s):  
Yasuto Sasaki ◽  
Junji Seki ◽  
John C Giddings ◽  
Junichiro Yamamoto
Keyword(s):  
Blood Flow ◽  
Thrombus Formation ◽  
Dependent Manner ◽  
Red Cell ◽  
Cell Velocity ◽  
Red Cell Velocity ◽  
The Mean ◽  
Wall Shear ◽  
Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

scholarly journals Anti-tumor activity of a novel proteasome inhibitor D395 against multiple myeloma and its lower cardiotoxicity compared with carfilzomib

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Xuxing Shen ◽  
Chao Wu ◽  
Meng Lei ◽  
Qing Yan ◽  
Haoyang Zhang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Proteasome Inhibitor ◽  
Osteoclast Differentiation ◽  
Dependent Manner ◽  
Serum Enzyme ◽  
Herg Channels ◽  
Anti Tumor Activity ◽  
Dose Dependent

AbstractCarfilzomib, a second-generation proteasome inhibitor, has significantly improved the survival rate of multiple myeloma (MM) patients, but its clinical application is still restricted by drug resistance and cardiotoxicity. Here, we identified a novel proteasome inhibitor, D395, and assessed its efficacy in treating MM as well as its cardiotoxicity at the preclinical level. The activities of purified and intracellular proteasomes were measured to determine the effect of D395 on the proteasome. CCK-8 and flow cytometry experiments were designed to evaluate the effects of D395 on cell growth and apoptosis. The effects of D395 and carfilzomib on serum enzyme activity, echocardiography features, cardiomyocyte morphology, and hERG channels were also compared. In our study, D395 was highly cytotoxic to MM cell lines and primary MM cells but not normal cells, and it was well tolerated in vivo. Similar to carfilzomib, D395 inhibited osteoclast differentiation in a dose-dependent manner. In particular, D395 exhibited lower cardiotoxicity than carfilzomib in all experiments. In conclusion, D395 is a novel irreversible proteasome inhibitor that has remarkable anti-MM activity and mild cardiotoxicity in vitro and in vivo.

scholarly journals Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 386
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh
Keyword(s):  
Stereotactic Body Radiation Therapy ◽  
In Vivo Studies ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Hep G2 ◽  
Time Curve ◽  
Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

STEROL SYNTHESIS IN RATS WITH EXPERIMENTALLY-INDUCED POLYCYSTIC OVARIES

1967 ◽  
Vol 39 (1) ◽  
pp. 53-60 ◽  
Author(s):  
W. C. ADAMS ◽  
J. H. LEATHEM
Keyword(s):  
Serum Cholesterol ◽  
Total Content ◽  
Gonadal Hormones ◽  
Female Rats ◽  
Cholesterol Concentration ◽  
Sterol Synthesis ◽  
Sterol Metabolism ◽  
Polycystic Ovaries ◽  
Immature Female

SUMMARY Immature female rats were fed thiouracil for 30 days and injected with 10 i.u. human chorionic gonadotrophin (HCG) for the last 20 days. In thiouracil-fed animals, HCG produced large ovaries containing follicular cysts. These ovaries showed a subnormal concentration of cholesterol but both a normal total content and normal incorporation of [1-14C]acetate into digitonin-precipitable-sterols. Liver and serum cholesterol concentrations were reduced, but in vivo, 4 hr. incorporation of acetate into sterols was doubled suggesting either an acceleration of cholesterol turnover or delayed utilization of sterol precursors of cholesterol. HCG also reduced ovarian cholesterol concentration in euthyroid animals but total organ content and incorporation of [14C]acetate were not altered, nor were liver and serum cholesterol affected. Since the effect of induced ovarian cysts on sterol metabolism cannot be accounted for by known effects of thyroid or gonadal hormones it is suggested that influences of steroid hormones on lipid metabolism may be greatly modified in thyroid deficiency.

Papaya shoot tip associated endophytic bacteria isolated from in vitro cultures and host–endophyte interaction in vitro and in vivo

2007 ◽  
Vol 53 (3) ◽  
pp. 380-390 ◽  
Author(s):  
Pious Thomas ◽  
Sima Kumari ◽  
Ganiga K. Swarna ◽  
T.K.S. Gowda
Keyword(s):  
Culture Medium ◽  
Carica Papaya ◽  
In Vitro Cultures ◽  
Dependent Manner ◽  
16S Rdna Sequence ◽  
16S Rdna Sequence Analysis ◽  
Single Organism ◽  
Dose Dependent

Fourteen distinct bacterial clones were isolated from surface-sterilized shoot tips (~1 cm) of papaya (Carica papaya L. ‘Surya’) planted on Murashige and Skoog (MS)-based papaya culture medium (23/50 nos.) during the 2–4 week period following in vitro culturing. These isolates were ascribed to six Gram-negative genera, namely Pantoea ( P. ananatis ), Enterobacter ( E. cloacae ), Brevundimonas ( B. aurantiaca ), Sphingomonas , Methylobacterium ( M. rhodesianum ), and Agrobacterium ( A. tumefaciens ) or two Gram-positive genera, Microbacterium ( M. esteraromaticum ) and Bacillus ( B. benzoevorans ) based on 16S rDNA sequence analysis. Pantoea ananatis was the most frequently isolated organism (70% of the cultures) followed by B. benzoevorans (13%), while others were isolated from single stocks. Bacteria-harboring in vitro cultures often showed a single organism. Pantoea, Enterobacter, and Agrobacterium spp. grew actively on MS-based normal papaya medium, while Microbacterium, Brevundimonas, Bacillus, Sphingomonas, and Methylobacterium spp. failed to grow in the absence of host tissue. Supplying MS medium with tissue extract enhanced the growth of all the organisms in a dose-dependent manner, indicating reliance of the endophyte on its host. Inoculation of papaya seeds with the endophytes (20 h at OD550 = 0.5) led to delayed germination or slow seedling growth initially. However, the inhibition was overcome by 3 months and the seedlings inoculated with Pantoea, Microbacterium, or Sphingomonas spp. displayed significantly better root and shoot growths.

Triphenyltin chloride induces spindle microtubule depolymerisation and inhibits meiotic maturation in mouse oocytes

2014 ◽  
Vol 26 (8) ◽  
pp. 1084 ◽  
Author(s):  
Yu-Ting Shen ◽  
Yue-Qiang Song ◽  
Xiao-Qin He ◽  
Fei Zhang ◽  
Xin Huang ◽  
...  
Keyword(s):  
Polar Body ◽  
Meiotic Maturation ◽  
Dependent Manner ◽  
Germinal Vesicle Breakdown ◽  
Mouse Oocytes ◽  
First Polar Body ◽  
Triphenyltin Chloride ◽  
Dose Dependent

Meiosis produces haploid gametes for sexual reproduction. Triphenyltin chloride (TPTCL) is a highly bioaccumulated and toxic environmental oestrogen; however, its effect on oocyte meiosis remains unknown. We examined the effect of TPTCL on mouse oocyte meiotic maturation in vitro and in vivo. In vitro, TPTCL inhibited germinal vesicle breakdown (GVBD) and first polar body extrusion (PBE) in a dose-dependent manner. The spindle microtubules completely disassembled and the chromosomes condensed after oocytes were exposed to 5 or 10 μg mL–1 TPTCL. γ-Tubulin protein was abnormally localised near chromosomes rather than on the spindle poles. In vivo, mice received TPTCL by oral gavage for 10 days. The general condition of the mice deteriorated and the ovary coefficient was reduced (P < 0.05). The number of secondary and mature ovarian follicles was significantly reduced by 10 mg kg–1 TPTCL (P < 0.05). GVBD decreased in a non-significant, dose-dependent manner (P > 0.05). PBE was inhibited with 10 mg kg–1 TPTCL (P < 0.05). The spindles of in vitro and in vivo metaphase II oocytes were disassembled with 10 mg kg–1 TPTCL. These results suggest that TPTCL seriously affects meiotic maturation by disturbing cell-cycle progression, disturbing the microtubule cytoskeleton and inhibiting follicle development in mouse oocytes.

Prolactin stimulates food intake in a dose-dependent manner

1989 ◽  
Vol 256 (1) ◽  
pp. R276-R280 ◽  
Author(s):  
T. Gerardo-Gettens ◽  
B. J. Moore ◽  
J. S. Stern ◽  
B. A. Horwitz
Keyword(s):  
Food Intake ◽  
Female Rats ◽  
High Dose ◽  
Dependent Manner ◽  
Additional Control ◽  
The Mean ◽  
Ovine Prolactin ◽  
Dose Dependent ◽  
Medium Dose ◽  
Cumulative Food Intake

Lactation in the rat is marked by pronounced hyperphagia and suppression of brown fat (BAT) thermogenic capacity. We previously examined the possibility that elevated prolactin levels mediate these changes. The present study evaluated the effect of varying prolactin levels on food intake, BAT mitochondrial GDP binding, and carcass adiposity. Female rats were injected daily for 10 days with ovine prolactin at one of three doses: high = 3.0, medium = 1.0, or low = 0.3 micrograms/g body wt. Controls were injected with 0.9% NaCl. A group of uninjected rats served as an additional control. Cumulative food intake was significantly elevated in a dose-dependent manner in the prolactin-treated animals relative to the saline-injected and uninjected controls. Compared with the saline controls, the mean cumulative food intake was greatest at the high dose (20% increase), intermediate at the medium dose (17%), and smallest at the low dose (12%). Prolactin-treated rats gained significantly more weight during the experiment than did controls. Despite the hyperphagia in the prolactin-treated rats, no significant differences in BAT mitochondrial GDP binding were observed among the five groups. These data indicate that elevated prolactin levels stimulate food intake in a dose-dependent manner and that this hyperphagia is not accompanied by an increase in BAT mitochondrial GDP binding.

scholarly journals The Antiinfective Effects of Velvet Antler of Formosan Sambar Deer (Cervus unicolor swinhoei) onStaphylococcus aureus-Infected Mice

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Ting-Yeu Dai ◽  
Chih-Hua Wang ◽  
Kun-Nan Chen ◽  
I-Nung Huang ◽  
Wei-Sheng Hong ◽  
...  
Keyword(s):  
Lipoteichoic Acid ◽  
Lavage Fluid ◽  
Dependent Manner ◽  
Protective Mechanisms ◽  
Velvet Antler ◽  
Sambar Deer ◽  
Dose Dependent ◽  
Cervus Unicolor

We assayed the effects of velvet antler (VA) of Formosan sambar deer (Cervus unicolor swinhoei) and its extracts on the anti-infective activity against pathogenicStaphylococcus aureus in vitroandin vivoin this study.In vitrodata indicated that the VA extracts stimulated the proliferation of resting splenocytes and macrophages in a dose-dependent manner up to the highest concentration used (150 μg mL−1). The production of proinflammatory cytokines (TNF-α, IL-6, IL-12) by lipoteichoic acid was significantly suppressed after being cocultured with the VA extracts in a dose-dependent manner. Animal test inS. aureus-infected mice demonstrated that the numbers of bacteria determined in the kidneys and peritoneal lavage fluid ofS. aureus-infected mice were significantly higher than those found in the same organs of mice pretreated with the VA samples. Moreover, the highly enhanced phagocytic activity of macrophages was further verified afterin vitrotreatment with the VA samples. The protective mechanisms of the VA samples might include an immune enhancer and an inflammatory cytokine suppressor.

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