Modulation of central glucocorticoid receptors in short- and long-term experimental hypothyroidism

Author(s):  
Elena Nikolopoulou ◽  
Dimitris Mytilinaios ◽  
Dimitris Spinos ◽  
Nikitas – Apollon Panagiotopoulos ◽  
George P. Chrousos

Aim: Normal adrenocortical responsiveness to stress involves glucocorticoid negative feedback to terminate hypothalamic-pituitary-adrenal (HPA) axis activation. Hypothyroidism is associated with a centrally mediated adrenal insufficiency associated. The aim of this study was to examine whether this may be explained by a disturbed glucocorticoid feedback through specific brain receptors: the mineralocorticoid (MR) and glucocorticoid receptor (GR). Methods: Cytosolic receptor binding and gene expression was assessed in male Sprague-Dawley rats (350gm) with short- (7 days) and long-standing (60 days) hypothyroidism (thyroidectomy). Glucocorticoid receptor number and binding affinity in the hippocampus were measured using radioreceptor assay. In situ hybridization was employed to examine GR and MRmRNA levels in the hippocampus and the pituitary. Results: No differences in receptor number or affinity were observed after 7days and 60days treatment. Increased GRmRNA expression in the anterior pituitary was observed in 7day hypothyroid rats under basal conditions compared to euthyroid rats (122.77+4.93 vs 99.65+4.83 DPM/mg; p<0.05), which was associated with significantly decreased GRmRNA levels after osmotic stress (100.82+2.8 vs 110.48+4.1 DPM/mg; p<0.05). No differences were observed at 60days. No effect on MR mRNA expression in the hippocampus was seen in basal condition after both 7- and 60days hypothyroidism. MRmRNA was significantly decreased in 60 days-hypothyroid rats compared to euthyroid after normal saline (3995.67+131.54 vs 5121.00+505.2 DPM/mg; p<0.05). Conclusion: Hypothyroidism resulted in significant changes in GR and MR mRNA levels, in the hippocampus and the pituitary, without changes in receptor number and binding affinity.

2000 ◽  
Vol 278 (4) ◽  
pp. F620-F627 ◽  
Author(s):  
Chairat Shayakul ◽  
Craig P. Smith ◽  
Harald S. Mackenzie ◽  
Wen-Sen Lee ◽  
Dennis Brown ◽  
...  

Regulation of urea concentration in the renal medullary interstitium is important for maintenance of hypertonicity and therefore the osmotic driving force for water reabsorption. Studies in Sprague-Dawley rats showed that restriction of water intake for 3 days results in upregulation of urea transporter (UT) mRNA in the inner stripe of outer medulla of the kidney (2.9-kb UT2) but not in the inner medulla (4.0-kb UT1). The present study was performed to investigate the role of vasopressin in long-term regulation of UT1 and UT2 in neurogenic diabetes insipidus (Brattleboro) rats treated with a 7-day continuous infusion of [Arg8]-vasopressin (AVP), [deamino-Cys1,d-Arg8]-vasopressin (dDAVP) or vehicle. Northern analysis showed that water restriction alone had no effect on the level of UT2 mRNA in vehicle-treated Brattleboro rats but UT2 mRNA markedly increased and UT1 mRNA modestly decreased after treatment with dDAVP. In situ hybridization further demonstrated that the UT2 signal is upregulated and spread along the descending thin limbs of loops of Henle and that UT1 signal is downregulated in the inner medullary collecting ducts in vasopressin-treated rats, with a greater response for dDAVP compared with the AVP-treated group. Immunocytochemistry studies revealed that the UT1 and UT2 proteins are also modified in the same pattern as the transcript changes. Our studies reveal the role of vasopressin in long-term regulation of UT1 and UT2 expression during water restriction.


1997 ◽  
Vol 273 (5) ◽  
pp. L1058-L1064 ◽  
Author(s):  
Christian Hierholzer ◽  
Edward Kelly ◽  
Katsuhiko Tsukada ◽  
Eric Loeffert ◽  
Simon Watkins ◽  
...  

Hemorrhagic shock (HS) initiates a series of inflammatory processes that includes the activation of polymorphonuclear granulocytic neutrophils (PMN). We tested the hypothesis that HS induces granulocyte colony-stimulating factor (G-CSF), a cytokine that augments PMN effector functions, in the lungs of rats. Sprague-Dawley rats were subjected to compensated or decompensated HS followed by resuscitation and death at 4 or 8 h. Animals subjected to HS demonstrated acute lung injury with PMN infiltration, edema, and hypoxia. Using semiquantitative reverse transcriptase-polymerase chain reaction, we detected a 1.9- to 7.1-fold increase in G-CSF mRNA levels in the lung of animals subjected to HS compared with sham controls. Levels of G-CSF mRNA increased with increased duration of the ischemic phase of resuscitated shock. In situ hybridization revealed that bronchoepithelial cells were the major cellular site of G-CSF mRNA. Thus production of G-CSF mRNA by bronchoepithelial cells is dramatically increased in a rat model of HS that also demonstrated lung injury. Increased local G-CSF levels may contribute to PMN recruitment and activation and resultant lung injury in HS.


1992 ◽  
Vol 262 (4) ◽  
pp. L489-L494 ◽  
Author(s):  
S. H. Guttentag ◽  
D. S. Phelps ◽  
W. Stenzel ◽  
J. B. Warshaw ◽  
J. Floros

The content and distribution of the 26-to 38-kDa surfactant protein (SP-A) and its mRNA were determined in fetuses of control and streptozotocin (STZ)-treated Sprague-Dawley rats using immunohistochemistry, RNA blotting, and in situ hybridization. Female rats were treated with 50 mg/kg STZ before mating, and the fetuses were killed at fetal days 18-21 or on neonatal days 1 and 2 (day of birth = end of day 22). SP-A was barely detectable on fetal day 18 in controls and easily detected by fetal day 21. In the STZ group, SP-A was decreased compared with controls at fetal days 18-21. However, by neonatal days 1–2, there were no significant differences in SP-A levels between groups. SP-A mRNA was detectable at fetal day 18 in controls, but it was decreased in the STZ group at day 18-21 (P less than 0.02) and differences were no longer detected by neonatal days 1–2. SP-A and SP-A mRNA accumulated with advancing gestational age in both groups until neonatal days 1–2. The differences in SP-A and SP-A mRNA levels in the two groups diminished with advancing age but remained significant at fetal day 21. These data suggest that STZ-induced diabetes interferes with normal expression of SP-A in the developing fetal lung.


1979 ◽  
Vol 13 (1) ◽  
pp. 17-20 ◽  
Author(s):  
Michael Paterson

A 7 year collection of calculi from short- and long-term studies with Sprague-Dawley rats showed that although the incidence of rats with urolithiasis was small (0·5%), the variety of sizes and composition of the calculi could be of general interest.


2021 ◽  
Author(s):  
Miguel Farinha-Ferreira ◽  
Nádia Rei ◽  
Jo&atildeo Fonseca-Gomes ◽  
Catarina Miranda-Lourenço ◽  
Paula Serr&atildeo ◽  
...  

Chronic adolescent cannabinoid receptor agonist exposure has been shown to lead to persistent increases in depressive-like behaviors. This has been a key obstacle to the development of cannabinoid-based therapeutics. However, most of the published work has been performed with only three compounds, namely ∆9-tetrahydrocannabinol, CP55,940 and WIN55,212-2. Hypothesizing that different compounds may lead to distinct outcomes, we herein used the highly potent CB1R/CB2R full agonist HU-210, and first aimed at replicating cannabinoid-induced long-lasting effects, by exposing adolescent female Sprague-Dawley rats to increasing doses of HU-210, for 11 days and testing them at adulthood, after a 30-day drug washout. Surprisingly, HU-210 did not significantly impact adult anxious- or depressive-like behaviors. We then tested whether chronic adolescent HU-210 treatment resulted in short-term (24h) alterations in depressive-like behavior. Remarkably, HU-210 treatment simultaneously induced marked antidepressant- and prodepressant-like responses, in the modified forced swim (mFST) and sucrose preference tests (SPT), respectively. Hypothesizing that mFST results were a misleading artifact of HU-210-induced behavioral hyperreactivity to stress, we assessed plasmatic noradrenaline and corticosterone levels, under basal conditions and following an acute swim-stress episode. Notably, we found that while HU-210 did not alter basal noradrenaline or corticosterone levels, it greatly augmented the stress-induced increase in both. Our results show that, contrary to previously studied cannabinoid receptor agonists, HU-210 does not induce persisting depressive-like alterations, despite inducing marked short-term increases in stress-induced reactivity. By showing that not all cannabinoid receptor agonists may induce long-term negative effects, these results hold significant relevance for the development of cannabinoid-based therapeutics.


1997 ◽  
Vol 19 (4) ◽  
pp. 368-374 ◽  
Author(s):  
Josephine M. Johns ◽  
Linda R. Noonan ◽  
Laura I. Zimmerman ◽  
Li Li ◽  
Cort A. Pedersen

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