scholarly journals Effects of long-term treatment with resveratrol and subcutaneous and oral estradiol administration on pituitary function in rats

2006 ◽  
Vol 189 (1) ◽  
pp. 77-88 ◽  
Author(s):  
Martina Böttner ◽  
Julie Christoffel ◽  
Hubertus Jarry ◽  
Wolfgang Wuttke

Hormone replacement therapy (HRT) has been used for several decades to treat menopausal discomforts. However, in the light of recent studies that draw attention to the potential hazards of conventional HRT, various attempts have been undertaken to search for alternatives to classical HRT. Phytoestrogens are claimed to be capable of positively influencing menopausal symptoms, including hot flushes. We designed a long-term study of 3 months to assess the effects of subcutaneous and orally fed 17β-estradiol (E2), as well as the actions of resveratrol (RES) on pituitary function in female rats. Our results have demonstrated that RES binds with a 10-fold lower affinity to estrogen receptor (ER)-α than to ERβ. The data from the in vivo study revealed that a dosage of 5 μg and 50 μg RES/kg bodyweight per day given to ovariectomized (OVX) rats achieved serum levels of 1.0 and 8.1 μM respectively. Long-term treatment of OVX rats with RES revealed no estrogenic potential on pituitary function in vivo as assessed by LH and prolactin secretion and by regulation of mRNAs for LHα, LHβ, and GnRH receptor. Subcutaneous treatment with E2 in silastic capsules exerted stronger effects on LH and prolactin secretion, as well as on LHβ, LHα, GnRH receptor, and ERβ mRNA regulation compared with orally applied estradiol benzoate despite comparable serum levels. Levels of aryl hydrocarbon receptor (AhR) mRNA in the pituitary were increased following OVX and attenuated by long-term E2 treatment, whereas RES did not modulate AhR mRNA expression.

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Luchao Li ◽  
Shuo Zhao ◽  
Zhengfang Liu ◽  
Nianzhao Zhang ◽  
Shuo Pang ◽  
...  

AbstractReceptor tyrosine kinase (RTK) inhibitors, such as sunitinib and sorafenib, remain the first-line drugs for the treatment of mRCC. Acquired drug resistance and metastasis are the main causes of treatment failure. However, in the case of metastasis Renal Cell Cancer (mRCC), which showed a good response to sunitinib, we found that long-term treatment with sunitinib could promote lysosome biosynthesis and exocytosis, thereby triggering the metastasis of RCC. By constructing sunitinib-resistant cell lines in vivo, we confirmed that TFE3 plays a key role in the acquired resistance to sunitinib in RCC. Under the stimulation of sunitinib, TFE3 continued to enter the nucleus, promoting the expression of endoplasmic reticulum (ER) protein E-Syt1. E-Syt1 and the lysosomal membrane protein Syt7 form a heterodimer, which induces ER fragmentation, Ca2+ release, and lysosomal exocytosis. Lysosomal exocytosis has two functions: pumping sunitinib out from the cytoplasm, which promotes resistance to sunitinib in RCC, releasing cathepsin B (CTSB) into the extracellular matrix (ECM), which can degrade the ECM to enhance the invasion and metastasis ability of RCC. Our study found that although sunitinib is an effective drug for the treatment of mRCC, once RCC has acquired resistance to sunitinib, sunitinib treatment will promote metastasis.


1994 ◽  
Vol 131 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Josef Marek ◽  
Václav Hána ◽  
Michal Kršek ◽  
Vlasta Justová ◽  
France Catus ◽  
...  

Marek J, Hána V. Kršek M. Justová V, Catus F, Thomas F. Long-term treatment of acromegaly with the slow-release somatostatin analogue lanreotide. Eur J Endocrinol 1994;131:20–6. ISSN 0804–4643 Thirteen patients with active acromegaly despite previous surgery were treated with 30 mg lanreotide im twice a month for 9 months. In 10 subjects the treatment continued to 19 months. GH serum levels of all patients decreased significantly from an initial value of 32.0 (29.4) μg/l [median (standard error of median)] to 10.0 (3.6) and 19.1 (5.7) after 3 and 9 months of treatment, respectively. In the 10 patients with the treatment longer than one year the decrease in GH was from 46.8 (29.4) μg/l to 12.5 (5.0) and 16.1 (5.3) after 13 and 19 months, respectively. IGF-I serum levels decreased significantly from 1193 (73)μg/l to 782 (99) and 621 (103) after 3 and 9 months, respectively, and were normalized in 3 patients. In the 10 patients treated for longer than one year, levels decreased significantly from 1318 (74)μg/l to 653 (170) and 742 (180) after 13 and 19 months, respectively. IGF BP-3 levels were reduced to the normal range in 6 patients and decreased from 8.7 (1.5)mg/l to 6.4 (0.8) and to 5.4 (1.0) after 3 and 9 months, respectively. In the patients with the 19 months treatment the decrease was from 9.3 (1.6) mg/l to 3.9 (0.9) and 4.8 (0.9) after 13 and 19 months, respectively. The IGF BP-3 to IFG I ratio increased in 7 patients. This elevation significantly correlated with the decrease in bioassayable somatomedin. Prolactin serum levels fell in all patients with increased prolactin secretion. Testosterone plasma levels increased in 4 out of 5 men without replacement therapy. Clinical improvement was observed in all patients. A reduction of tumour mass was observed in five patients and complete disappearance of the tumour in one subject. All patients complained of mild abdominal pain and softened stools for several days following the injections. However, these side effects never required interruption of treatment. Asymptomatic microlithiasis was seen in only one patient after 13 months, which led to treatment being suspended for a period of 3 months after which it was resumed. Fasting serum insulin and insulin area under the curve (AUC) after oral glucose tolerance test (OGTT) fell in all patients. Fasting blood glucose, fructosamine and glucose AUC after OGTT slightly increased during the treatment, but all blood glucose levels (fasting and during OGTT) remained within normal ranges. Lanreotide appears to be a safe and effective treatment in patients with active acromegaly unresolved by surgery. The long-acting formulation avoids the drawbacks associated with either repeated daily injections or continuous infusions of somatostatin analogues. Josef Marek, Third Department of Medicine, Charles University, U nemocnice 1, 128 21 Praha 2, The Czech Republic


Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Nildris Cruz Diaz ◽  
A'ja V Duncan ◽  
Wayne Graham ◽  
Brian Westwood ◽  
Patricia E. Gallagher ◽  
...  

Physical performance and systolic blood pressure (SBP) during aging in normotensive female Sprague-Dawley (SD) and hypertensive (mRen2)27 transgenic rats were assessed following long-term treatment with a Muscadine Grape Extract (MGE, Piedmont Research and Development Corp). MGE was administered at a dose of 0.2 mg/mL in the drinking water starting at 14 weeks (wks) of age with an endpoint at 70 wks of age (total time of treatment of 56 wks). At 20-, 40- and 70-wks of age, physical performance (exercise capacity in seconds and workload in grams - meters) was determined using a treadmill at a velocity of 17 cm/second with a 5% incline. SBP was determined by tail-cuff plethysmography in trained rats. There were no significant differences in physical performance between SD and (mRen2)27 female rats at any age despite the higher SBP in the (mRen2)27 rats at all ages. Long-term treatment with MGE had no significant effect on physical performance or SBP in SD rats at any age. In contrast, MGE treatment markedly increased exercise capacity (40 wks: 1615 ± 166 vs 4943 ± 442 seconds, p<0.01, n = 4-9; 70 wks: 2520 ± 374 vs 4117 ± 245 seconds, p<0.01, n = 4-8) and workload (40 wks: 4579 ± 490 vs 14730 ± 1353 grams - meters, p<0.01, n = 4-9; 70 wks: 8338 ± 1340 vs 13659 ± 933 grams - meters, p<0.01, n = 4-8) at the later ages in female (mRen2)27 rats, while there was no effect on SBP (20 wks: 167 ± 4 vs 173 ± 4 mm Hg, n = 4-6; 40 wks: 177 ± 8 vs 170 ± 7 mm Hg, n = 6-7; 70 wks:154 ± 6 vs 172 ± 6 mm Hg, n = 5) at any age. These data suggest that MGE treatment is effective in improving physical performance only in hypertensive female rats and may be independent of changes in blood pressure. The benefit of MGE in the older hypertensive female may reflect reductions in vascular stiffness and oxidative stress. Support: Chronic Disease Research Fund, Hypertension & Vascular Research Center


1996 ◽  
Vol 10 (4) ◽  
pp. 541-545 ◽  
Author(s):  
B. E. SCHENK ◽  
H. P. M. FESTEN ◽  
E. J. KUIPERS ◽  
E. C. KLINKENBERG-KNOL ◽  
S. G. M. MEUWISSEN

1986 ◽  
Vol 9 (5) ◽  
pp. 301-304 ◽  
Author(s):  
S. Stefoni ◽  
A. Nanni Costa ◽  
G. Liviano D'Arcangelo ◽  
M. Biavati ◽  
S. lannelli ◽  
...  

Biocompatibility of charcoal hemoperfusion was studied in a group of 15 uremic patients, evaluating the effects of long-term treatment on some structural and functional parameters of circulating lymphocytes: in vivo distribution of T-cell subsets; surface T3, T4 and T8 antigen expression, in vivo and in vitro DNA synthesis. A comparative analysis was performed with patients on conventional dialysis using cuprophan membranes.


1971 ◽  
Vol 68 (3) ◽  
pp. 585-596 ◽  
Author(s):  
O. Helmer Serensen ◽  
Inge Hindberg

ABSTRACT The influence of short-term and long-term treatment with gonadal hormones on the response to calcitonin was investigated in the rat. Oestrogen-treatment, short-term as well as long-term, resulted in a reduced responsiveness to calcitonin. Long-term treatment with androgens enhanced the hypocalcaemic effect of calcitonin in castrated rats of either sex, but reduced the effect in intact animals. No sex differences could be registered in the sensitivity to calcitonin, when intact animals were compared according to age, while marked differences were observed, when the animals were compared according to weight. There was a linear decrease in the response to calcitonin with increasing age in rats of both sexes. An intraperitoneal calcium load was followed by an acute rise in the serum calcium levels. The adult animals counteracted the hypercalcaemia more slowly than the young ones. Significant differences also occurred between male and female rats, the rise in the serum calcium concentration being much more pronounced in the latter group. The hypocalcaemic activity of thyroid tissue from rats of both sexes and of various ages showed considerable variations, but no differences correlated to age or sex.


PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e50853 ◽  
Author(s):  
Silje Skrede ◽  
Johan Fernø ◽  
Bodil Bjørndal ◽  
Wenche Rødseth Brede ◽  
Pavol Bohov ◽  
...  

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