Maternal Exposure to a Low Dose of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Suppressed the Development of Reproductive Organs of Male Rats: Dose-Dependent Increase of mRNA Levels of 5 -Reductase Type 2 in Contrast to Decrease of Androgen Receptor in the Pubertal Ventral Prostate

Abstract Brief exposure of male rats to estrogens during the neonatal period interrupts normal prostate development, alters epithelial cell differentiation, and predisposes this gland to hyperplasia and severe dysplasia analogous to prostatic intraepithelial neoplasia (PIN) with aging. Previous work demonstrated that the reduced growth, secretory activity, and androgen sensitivity that are observed in the adult ventral lobe are a function of reduced androgen receptor (AR) levels. Down-regulation of AR protein was found to occur immediately following neonatal exposure to estradiol benzoate (EB) and persist through adulthood and aging, indicating a permanent imprint on the ability of the prostate to express normal AR levels. To determine the intracellular mechanism of AR down-regulation by estrogens, the present study examined the effect of neonatal EB on AR gene transcription, mRNA levels, protein translation, and protein degradation in the d 10 ventral prostate glands. Nuclear run-on assays showed no alteration in AR gene transcription following exposure to EB on d 1–5 compared with controls. In situ hybridization and quantitative (q) RT-PCR revealed no difference in mRNA levels in the stromal or epithelial cells in response to estrogen exposure which, taken together, indicate that estrogen down-regulation of AR is mediated at the posttranscriptional level. AR translation was assessed with an in vitro transcription-translation assay in the presence of prostatic lysates from oil and estrogen-exposed animals, and no treatment effect was noted. AR degradation was examined in an in vitro assay validated with adult intact and castrate prostates. Prostatic lysates from intact rats initiated AR degradation with a t1/2 of 2.31 h, whereas proteins from castrate rats accelerated AR degradation to a t1/2 of 1.34 h (P < 0.001). Prostatic lysates from control d 10 prostates induced AR degradation with a t1/2 of 1.49 h, whereas estrogenized prostates increased AR degradation to a t1/2 of 1.11 h (P < 0.001). Proteosome inhibitors MG132 and ALLnL were able to reverse AR degradation induced by prostatic lysates from adult intact and castrate rats as well as from developing and estrogenized prostates, indicating that AR degradation was mediated through the proteosome pathway. Furthermore, the proteosome-mediated AR degradation in the estrogenized d 10 prostate was associated with a marked suppression of Akt phosphorylation that has been linked to AR degradation in other systems. Taken together, the present data show that exposure to neonatal estrogens down-regulates AR protein levels in the ventral prostate gland by accelerating AR degradation, which is mediated through the proteosome pathway.

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Thyroid hormone and glucocorticoid regulation of pituitary growth hormone-releasing hormone receptor gene expression

Journal of Endocrinology ◽

10.1677/joe.0.152r013 ◽

1997 ◽

Vol 152 (2) ◽

pp. R13-R17 ◽

Cited By ~ 34

Author(s):

A I Korytko ◽

L Cuttler

Keyword(s):

Gene Expression ◽

Thyroid Hormone ◽

Hormone Receptor ◽

Male Rats ◽

Pituitary Cells ◽

Mrna Levels ◽

R Gene ◽

Releasing Hormone ◽

Dose Dependent Increase ◽

Dose Dependent

Abstract The GH-releasing hormone receptor (GHRH-R) is a critical link between hypothalamic GH-releasing hormone (GHRH) and pituitary GH secretion. However, the factors that regulate GHRH-R are not well understood. Despite the importance of thyroid hormone and glucocorticoids in influencing the GH axis in vivo, it is not known whether these hormones act directly at the pituitary to regulate expression of GHRH-R. We tested the effects of T3 and hydrocortisone on GHRH-R gene expression in primary pituitary cell cultures of adult male rats. Pituitary cells were treated for 24 h with increasing concentrations of T3 (0.06-60 nM) or hydrocortisone (2.8 nM-2.8 μM). GHRH-R mRNA levels were assessed by ribonuclease protection assay. T3 caused a striking dose-dependent increase in GHRH-R mRNA, reaching levels 5.1 ± 0.5 fold over controls (P<0·001). Hydrocortisone also stimulated a marked dose-dependent increase in GHRH-R mRNA, reaching levels 5.6 ± 0.7 fold over controls (P<0·001). Combined treatment with both hormones did not cause further augmentation of GHRH-R mRNA levels. These data indicate that T3 and hydrocortisone act directly at the pituitary as potent regulators of GHRH-R gene expression.

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Increased Urinary Excretion of Carnitine and Acylcarnitine by Mercuric Chloride Is Reversed by 2,3-Dimercapto-1-Propanesulfonic Acid in Rats

International Journal of Toxicology ◽

10.1177/1091581810364852 ◽

2010 ◽

Vol 29 (3) ◽

pp. 313-317

Author(s):

Waleed A. Al-Madani ◽

Nikhat J. Siddiqi ◽

Abdullah S. Alhomida ◽

Haseeb A. Khan ◽

Ibrahim A. Arif ◽

...

Keyword(s):

Body Weight ◽

Urinary Excretion ◽

Mercuric Chloride ◽

Free Carnitine ◽

Male Rats ◽

Significant Protection ◽

Total Carnitine ◽

Dose Dependent Increase ◽

Dose Dependent ◽

Wistar Male Rats

This investigation was aimed to study the effect of 2,3-dimercapto-1-propanesulfonic acid (DMPS) on mercuric chloride (HgCl2)-induced alterations in urinary excretion of various carnitine fractions including free carnitine (FC), acylcarnitine (AC), and total carnitine (TC). Different groups of Wistar male rats were treated with HgCl2 at the doses of 0.1, 0.5, 1.0, 2.0, and 3.0 mg/kg body weight, and the animals were sacrificed at 24 hours following HgCl2 injection. A separate batch of animals received HgCl2 (2 mg/kg) with or without DMPS (100 mg/kg) and sacrificed at 24 or 48 hours after dosing. Administration of HgCl2 resulted in statistically significant and dose-dependent increase in the urinary excretion of FC, AC, and TC in rats. However, the ratio of urinary AC:FC was significantly decreased by HgCl2. Pretreatment with DMPS offered statistically significant protection against HgCl2-induced alterations in various urinary carnitine fractions in rats.

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Regulation of food intake by neuropeptide Y in goldfish

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.279.3.r1025 ◽

2000 ◽

Vol 279 (3) ◽

pp. R1025-R1034 ◽

Cited By ~ 115

Author(s):

Yuwaraj K. Narnaware ◽

Pierre P. Peyon ◽

Xinwei Lin ◽

Richard E. Peter

Keyword(s):

Food Intake ◽

Neuropeptide Y ◽

Mrna Levels ◽

Food Ration ◽

Y1 Receptor ◽

Daily Food ◽

Daily Food Ration ◽

Brain Ventricle ◽

Dose Dependent Increase ◽

Dose Dependent

In mammals, neuropeptide Y (NPY) is a potent orexigenic factor. In the present study, third brain ventricle (intracerebroventricular) injection of goldfish NPY (gNPY) caused a dose-dependent increase in food intake in goldfish, and intracerebroventricular administration of NPY Y1-receptor antagonist BIBP-3226 decreased food intake; the actions of gNPY were blocked by simultaneous injection of BIBP-3226. Goldfish maintained on a daily scheduled feeding regimen display an increase in NPY mRNA levels in the telencephalon-preoptic area and hypothalamus shortly before feeding; however, a decrease occured in optic tectum-thalamus. In both fed and unfed fish, brain NPY mRNA levels decreased after scheduled feeding. Restriction in daily food ration intake for 1 wk or food deprivation for 72 h resulted in increased brain NPY mRNA levels. Results from these studies demonstrate that NPY is a physiological brain signal involved in feeding behavior in goldfish, mediating its effects, at least in part, through Y1-like receptors in the brain.

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Acute pulmonary effects of aerosolized nicotine

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00564.2017 ◽

2019 ◽

Vol 316 (1) ◽

pp. L94-L104 ◽

Cited By ~ 21

Author(s):

Shama Ahmad ◽

Iram Zafar ◽

Nithya Mariappan ◽

Maroof Husain ◽

Chih-Chang Wei ◽

...

Keyword(s):

Electronic Cigarettes ◽

White Blood Cells ◽

Weight Ratio ◽

Airway Epithelial Cells ◽

Mrna Levels ◽

Safe Alternative ◽

Arterial Blood ◽

Dose Dependent Increase ◽

Dose Dependent ◽

E Cadherin

Nicotine is a highly addictive principal component of both tobacco and electronic cigarette that is readily absorbed in blood. Nicotine-containing electronic cigarettes are promoted as a safe alternative to cigarette smoking. However, the isolated effects of inhaled nicotine are largely unknown. Here we report a novel rat model of aerosolized nicotine with a particle size (~1 μm) in the respirable diameter range. Acute nicotine inhalation caused increased pulmonary edema and lung injury as measured by enhanced bronchoalveolar lavage fluid protein, IgM, lung wet-to-dry weight ratio, and high-mobility group box 1 (HMGB1) protein and decreased lung E-cadherin protein. Immunohistochemical analysis revealed congested blood vessels and increased neutrophil infiltration. Lung myeloperoxidase mRNA and protein increased in the nicotine-exposed rats. Complete blood counts also showed an increase in neutrophils, white blood cells, eosinophils, and basophils. Arterial blood gas measurements showed an increase in lactate. Lungs of nicotine-inhaling animals revealed increased mRNA levels of IL-1A and CXCL1. There was also an increase in IL-1α protein. In in vitro air-liquid interface cultures of airway epithelial cells, there was a dose dependent increase in HMGB1 release with nicotine treatment. Air-liquid cultures exposed to nicotine also resulted in a dose-dependent loss of barrier as measured by transepithelial electrical resistance and a decrease in E-cadherin expression. Nicotine also caused a dose-dependent increase in epithelial cell death and an increase in caspase-3/7 activities. These results show that the nicotine content of electronic cigarettes may have adverse pulmonary and systemic effects.

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Effects of the inflammatory mediator prostaglandin D2 on submucosal neurons and secretion in guinea pig colon

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1994.266.1.g132 ◽

1994 ◽

Vol 266 (1) ◽

pp. G132-G139 ◽

Cited By ~ 12

Author(s):

T. Frieling ◽

C. Rupprecht ◽

A. B. Kroese ◽

M. Schemann

Keyword(s):

Guinea Pig ◽

Ganglion Cells ◽

Short Circuit ◽

Short Circuit Current ◽

Chloride Secretion ◽

Prostaglandin D2 ◽

Flux Chamber ◽

Dose Dependent Increase ◽

Dose Dependent

Conventional flux chamber and intracellular recording methods were used to investigate the mode of action of prostaglandin D2 (PGD2) on ion transport in muscle-stripped segments of guinea pig colon and on colonic submucosal ganglion cells. Application of PGD2 resulted in a dose-dependent increase in short-circuit current that was reduced by serosal addition of bumetanide, tetrodotoxin, atropine, or piroxicam, but not hexamethonium. Application of PGD2 to submucosal neurons evoked a depolarization of the membrane potential that was associated with an enhanced spike discharge. In AH/type 2 neurons, postspike afterhyperpolarizations were reduced in amplitude and duration. The depolarizing responses to PGD2 were not affected by tetrodotoxin, indicative of a direct effect of PGD2 on the impaled neurons. Whereas fast excitatory postsynaptic potentials (EPSPs) were not affected by PGD2, slow EPSPs were reduced by a presynaptic effect, indicating presynaptic suppression of noncholinergic neurotransmitter release. The study demonstrates that PGD2 acts as a neuromodulator to evoke nerve-mediated chloride secretion, predominantly through activation of cholinergic submucosal neurons. The results further indicate that PGD2 released from lamina propria immune cells during antigenic stimulation may influence mucosal function by altering electrical behavior of submucosal neurons.

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Luteinizing Hormone and Human Chorionic Gonadotropin Decrease Type 2 5α-Reductase and Androgen Receptor Protein Levels in Women’s Skin

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.83.5.4767 ◽

1998 ◽

Vol 83 (5) ◽

pp. 1776-1782 ◽

Cited By ~ 1

Author(s):

J. Bird ◽

X. Li ◽

Z. M. Lei ◽

J. Sanfilippo ◽

M. A. Yussman ◽

...

Keyword(s):

Androgen Receptor ◽

Androgen Receptors ◽

Clinical Importance ◽

Receptor Protein ◽

Glycoprotein Hormone ◽

Protein Levels ◽

Androgen Receptor Protein ◽

Dose Dependent ◽

Skin Samples

The present study tested the hypothesis that LH/hCG may regulate the type 2 5α-reductase and androgen receptor protein levels in skin. The skin samples obtained from women undergoing abdominal laparotomy or abdominoplasty were incubated in the presence or absence of hCG. Western blotting was then performed to determine the response of type 2 5α-reductase and androgen receptors. The results demonstrated that treatment with hCG resulted in a significant time- and dose-dependent, although modest, decrease in 5α-reductase and androgen receptor levels compared to the controls. These effects were mimicked by LH, but not by other hormones in the glycoprotein hormone family, includingα - and β-subunits of hCG. Although the biological and clinical importance of this regulation remains to be determined, these findings reaffirm that human skin is among the nongonadal tissues that respond to LH and hCG treatment.

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Molecular Mechanism Underlying the Antidiabetic Effects of a Siddha Polyherbal Preparation in the Liver of Type 2 Diabetic Adult Male Rats

Journal of Evidence-Based Complementary & Alternative Medicine ◽

10.1177/2156587212460047 ◽

2012 ◽

Vol 18 (1) ◽

pp. 29-42 ◽

Cited By ~ 1

Author(s):

Venkataraman Balaji ◽

Jayaraman Selvaraj ◽

Sampath Sathish ◽

Chinnaiyan Mayilvanan ◽

Karundevi Balasubramanian

Keyword(s):

Insulin Receptor ◽

Molecular Mechanism ◽

Diabetic Rats ◽

Male Rats ◽

Tinospora Cordifolia ◽

Syzygium Aromaticum ◽

Mrna Levels ◽

Type 2 Diabetic ◽

Antidiabetic Effects

A siddha polyherbal preparation consisting of 5 medicinal plants, namely, Asparagus racemosus, Emblica officinalis, Salacia oblonga, Syzygium aromaticum, and Tinospora cordifolia, in equal ratio, was formulated to examine the molecular mechanism by which it exhibits antidiabetic effects in the liver of high-fat and fructose-induced type 2 diabetic rats. The polyherbal preparation treated type 2 diabetic rats showed an increase in insulin receptor, Akt, and glucose transporter2 mRNA levels compared with diabetic rats. Insulin receptor, insulin receptor substrate-2, Akt, phosphorylated Akt substrate of 160kDaThreonine642, α-Actinin-4, β-arrestin-2, and glucose transporter2 proteins were also markedly decreased in diabetic rats, whereas the polyherbal preparation treatment significantly improved the expression of these proteins more than that of metformin-treated diabetic rats. The expression pattern of insulin signaling molecules analyzed in the present study signifies the therapeutic efficacy of the siddha polyherbal preparation.

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The Characterization of High-Fat Diet and Multiple Low-Dose Streptozotocin Induced Type 2 Diabetes Rat Model

Experimental Diabetes Research ◽

10.1155/2008/704045 ◽

2008 ◽

Vol 2008 ◽

pp. 1-9 ◽

Cited By ~ 211

Author(s):

Ming Zhang ◽

Xiao-Yan Lv ◽

Jing Li ◽

Zhi-Gang Xu ◽

Li Chen

Keyword(s):

Type 2 Diabetes ◽

Animal Model ◽

High Fat Diet ◽

Low Dose ◽

Tolerance Test ◽

Male Rats ◽

High Fat ◽

New Model ◽

Injection Group

Aim. Based on the previously established method, we developed a better and stable animal model of type 2 diabetes mellitus by high-fat diet combined with multiple low-dose STZ injections. Meanwhile, this new model was used to evaluate the antidiabetic effect of berberine.Method. Wistar male rats fed with regular chow for 4 weeks received vehicle (control groups), rats fed with high-fat diet for 4 weeks received different amounts of STZ once or twice by intraperitoneal injection (diabetic model groups), and diabetic rats were treated with berberine (100 mg/kg, berberine treatment group). Intraperitoneal glucose tolerance test and insulin tolerance test were carried out. Moreover, fasting blood glucose, fasting insulin, total cholesterol, and triglyceride were measured to evaluate the dynamic blood sugar and lipid metabolism.Result. The highest successful rate (100%) was observed in rats treated with a single injection of 45 mg/kg STZ, but the plasma insulin level of this particular group was significantly decreased, and ISI has no difference compared to control group. The successful rate of 30 mg/kg STZ twice injection group was significantly high (85%) and the rats in this group presented a typical characteristic of T2DM as insulin resistance, hyperglycemia, and blood lipid disorder. All these symptoms observed in the 30 mg/kg STZ twice injection group were recovered by the treatment of berberine.Conclusion. Together, these results indicated that high-fat diet combined with multiple low doses of STZ (30 mg/kg at weekly intervals for 2 weeks) proved to be a better way for developing a stable animal model of type 2 diabetes, and this new model may be suitable for pharmaceutical screening.

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INHIBITORY ACTION OF CORTISONE ON TESTOSTERONE-INDUCED GROWTH OF THE VENTRAL PROSTATE, THE DORSOLATERAL PROSTATE, THE COAGULATING GLANDS AND THE SEMINAL VESICLES IN CASTRATED ADRENALECTOMIZED RATS

Acta Endocrinologica ◽

10.1530/acta.0.0690359 ◽

1972 ◽

Vol 69 (2) ◽

pp. 359-368 ◽

Cited By ~ 1

Author(s):

Lars-Eric Tisell

Keyword(s):

Inhibitory Action ◽

Testosterone Propionate ◽

Reproductive Organs ◽

Inhibitory Effect ◽

Seminal Vesicles ◽

Male Rats ◽

Ventral Prostate ◽

Adrenal Steroids ◽

Androgenic Effect ◽

Adrenalectomized Rats

ABSTRACT The weight and histology of the ventral and dorsolateral prostate, the coagulating glands and the seminal vesicles were studied in castrated non-adrenalectomized male rats after sixteen days of daily injections of testosterone propionate and in castrated adrenalectomized rats after daily injections of testosterone propionate alone or in combination with cortisone. Testosterone propionate was given in daily doses of 0.020 mg and cortisone in daily doses of 1 mg, 3 mg or 9 mg. Testosterone alone induced a less pronounced growth of the dorsolateral prostate, the coagulating glands and the seminal vesicles in castrated non-adrenalectomized than in castrated adrenalectomized rats, suggesting an inhibitory effect of adrenal steroids on the action of testosterone. Cortisone which has a weak androgenic effect when given alone, partially counteracted the testosterone induced growth of the accessory reproductive organs in castrated adrenalectomized rats.

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