scholarly journals Short-Term Estradiol Administration in Aging Ovariectomized Rats Provides Lasting Benefits for Memory and the Hippocampus: A Role for Insulin-Like Growth Factor-I

Endocrinology ◽  
2012 ◽  
Vol 154 (2) ◽  
pp. 842-852 ◽  
Author(s):  
Christine F. Witty ◽  
Layne P. Gardella ◽  
Maria C. Perez ◽  
Jill M. Daniel

We previously demonstrated that aged ovariectomized rats that had received prior estradiol treatment in middle age exhibited enhanced spatial memory and increased levels of estrogen receptor (ER)-α in the hippocampus long after estradiol treatment was terminated. The implication for cognition of increased levels of ERα resulting from prior estradiol exposure is unknown. In the absence of estrogens, growth factors, including IGF-I, can induce ERα-mediated transcription through ligand-independent mechanisms. Our current goal was to determine whether IGF-I mediates the ability of short-term exposure to estradiol to exert long-term effects on cognition and the hippocampus of aging females. Ovariectomized middle-aged rats were implanted with estradiol or cholesterol vehicle capsules. After 40 days, all capsules were removed and drug treatments were initiated. Half of each hormone treatment group received chronic intracerebroventricular delivery of the IGF-I receptor antagonist JB1, and the other half received artificial cerebrospinal fluid vehicle. Rats were tested on a spatial memory radial-arm maze task and hippocampi were immunostained for proteins of interest by Western blotting. As expected, previous treatment with estradiol enhanced spatial memory and increased levels of ERα in the hippocampus. JB1 reversed these effects. Previous treatment with estradiol resulted in lasting increases in levels of IGF-I receptors and phosphorylation of ERK/MAPK, a downstream signaling molecule of both ERα and IGF-I receptors, and increased levels of the ERα-regulated protein, choline acetyltransferase. JB1 blocked effects on ERK/MAPK and choline acetyltransferase. Results indicate that activation of IGF-I receptors is necessary for prior estradiol exposure to exert lasting impact on the hippocampus and memory.

1985 ◽  
Vol 248 (6) ◽  
pp. E706-E711 ◽  
Author(s):  
J. P. van Putten ◽  
H. M. Krans

Catecholamines are known to have short-term regulatory effects on fat cell hexose uptake. We examined the long-term effects of catecholamines on the insulin-sensitive 2-deoxyglucose (dGlc) uptake in cultured 3T3-L1 adipocytes. Prolonged exposure (48 h) to isoproterenol (beta-adrenergic agonist) stimulated the basal dGlc uptake up to 90%. The effect was specific, time, concentration, and protein synthesis dependent and reversible. The effect of insulin was unaltered and superimposed on the increase in basal dGlc uptake. The long-term effect of isoproterenol was mimicked by epinephrine, dibutyryl cAMP (DBcAMP), and 1-methyl-3-isobutylxanthine (IBMX). By contrast, short-term exposure to isoproterenol (and epinephrine) induced a protein synthesis-independent increase in basal dGlc uptake (30%) not accompanied by an increase in insulin responsiveness. Moreover, on short-term basis, DBcAMP and IBMX suppressed both the basal and insulin-stimulated uptake up to 50%. Determination of the intracellular nonphosphorylated dGlc during the uptake and of the hexokinase activity revealed that the long-term effect of isoproterenol was most likely due to alterations low in dGlc transport. In conclusion, long-term regulators of hexose uptake are in cultured 3T3-L1 adipocytes, isoproterenol, and other cAMP stimulators. The long-term effect is independent from the short-term regulatory effect of the agents and from the effect of insulin.


1995 ◽  
Vol 73 (11) ◽  
pp. 1582-1588 ◽  
Author(s):  
David W. Silversides ◽  
Christopher A. Price ◽  
Gerard M. Cooke

To determine if and when short-term ablation of androgen action compromises the development of the male reproductive tract in mice, the androgen receptor antagonist hydroxyflutamide was administered orally to pregnant FVB/N mice and the reproductive tracts of the male offspring were examined when adult. Hydroxyflutamide (30 mg per day) for 5 days from day 11 to day 15 of gestation caused hypospadias in all male progeny. However, testis weights, seminal vesicle weights, and serum testosterone levels were not affected (p > 0.05) but caput–corpus epididymal weights were 15% lower than controls (p < 0.02). Shorter periods of treatment that included day 14 or 15 caused hypospadias, but treatments that did not include days 14 and 15 did not (p < 0.002). Hydroxyflutamide (30 mg, once or twice daily for 2 consecutive days) between days 15 and 20 of gestation demonstrated that androgen ablation on days 15&16 caused hypospadias, absence of prostate, and scrotal location of the seminal vesicles with abdominal testes (p < 0.05). Males exposed later in pregnancy had prostates, but the weights were reduced (p < 0.001); testes were scrotal and seminal vesicles were abdominal; caput–corpus epididymal weights were 15–30% lower than controls (p < 0.05), but the tubule contained large numbers of spermatozoa. Furthermore, testis weights, serum testosterone, and the response of the testis to a human chorionic gonadotropin (hCG) challenge in vitro were not compromised by hydroxyflutamide, and seminiferous tubules exhibited normal spermatogenesis. When males that had been exposed to hydroxyflutamide on days 13&14, 15&16, 17&18, and 19&20 were housed with sexually mature females, pregnancies resulted only from the day 19&20 treatment group. Thus, there are long-term effects caused by short-term blockade of androgen action at critical times during pregnancy and such effects could result in the inability to impregnate, irrespective of any externally visible indications of developmental anomalies.Key words: antiandrogen, sexual development, fetus, male, mouse.


2018 ◽  
Vol 37 (1) ◽  
pp. 18-27 ◽  
Author(s):  
Fernanda Rossi Paolillo ◽  
Renan Arnon Romano ◽  
Luciana de Matos ◽  
Airton Abrahão Martin ◽  
Francisco Eduardo Gontijo Guimarães ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Fatima Benaissa ◽  
Cara Nichole Maesano ◽  
Rezak Alkama ◽  
Isabella Annesi-Maesano

We used Health Impact Assessment (HIA) to analyze the impact on a given population’s health outcomes in terms of all-causes mortality and respiratory and cardiovascular hospitalizations attributable to short-term exposure to particulate matter less than 10 μm diameter (PM10) in Bejaia city, for which health effects of air pollution have never been investigated. Two scenarios of PM10reduction were considered: first, a scenario where the PM10annual mean is decreased by 5 µg/m3, and then a scenario where this PM10mean is decreased to 20 µg/m3(World Health Organization annual air quality guideline (WHO-AQG)). Annual mean level of PM10(81.7 µg/m3) was calculated from objective measurements assessedin situ. Each year, about 4 and 55 deaths could be postponed with the first and the second scenarios successfully. Furthermore, decreasing PM10annual mean by 5 µg/m3would avoid 5 and 3 respiratory and cardiac hospitalizations, respectively, and not exceeding the PM10WHO-AQG (20 µg/m3) would result in a potential gain of 36 and 23 per 100000 respiratory and cardiac hospitalizations, respectively. Lowering in current levels of PM10has a nonnegligible impact in terms of public health that it is expected to be higher in the case of long-term effects.


2020 ◽  
Author(s):  
Samar El Kholy ◽  
John P. Giesy ◽  
Yahya Al Naggar

AbstractNanoparticles of cadmium oxide (CdO NPs) are among the most common industrial metal oxide nanoparticles. Early adulthood (F0) fruit flies (D. melanogaster) were exposed for 7 days to a sub lethal concentration (0.03 mg CdO NPs/ml, which was 20% of the LC50), spiked into food media to test for long term-effects over time and beyond their direct exposure on key life history traits. Effects on survival, developmental time, eclosion rate, fecundity and negative geotaxis performance were assessed. Potential effects on ultrastructure of mid gut cells were also investigated by use of electron microscopy. All studied life history traits, as well as climbing behavior were adversely affected by exposure to CdO NPs. In non-exposed progeny (F1) of adult flies (F0), a blistered wing phenotype was also observed. Lysis of nuclear and rough endoplasmic reticulum (rER) membranes, mitochondrial swelling and lysis were among the most common cellular alterations observed in midgut cells of F0 flies exposed to CdO NPs. Genes encoding for metallothionein (MTn A-D) were significantly upregulated in both parent flies (F0) and their progeny (F1) after exposure of F0 flies to CdO NPs, compared to unexposed, control flies, a result which indicated potential, long-term effects. Taken together, these results suggest that short-term exposure to a sublethal concentration of CdO NPs is sufficient to cause long-lasting, harmful effects on fruit flies.Graphical Abstract


1987 ◽  
Vol 115 (4) ◽  
pp. 483-489 ◽  
Author(s):  
John S. M. De Mellow ◽  
David J. Handelsman ◽  
Robert C. Baxter

Abstract. The effect of short-term exposure to the insulin-like growth factors (IGF-I and IGF-II) on testosterone production by rat testicular interstitial cells in primary culture has been examined. Both peptides, when present during a 1-h pre-incubation period, increased human chorionic gonadotropin (hCG)-stimulated testosterone release over the following 16-h period. The effect of exposure to IGFs was most marked on maximally hCG-stimulated testosterone release. Maximal stimulation following IGF exposure was 80– 85% above that seen without IGFs, and the IGF effect was half-maximal at 1.5–2 μg/l of IGF-I or IGF-II. Pre-incubation with IGFs did not alter the concentration of hCG (0.1 μg/l) at which half-maximal stimulation of testosterone release was seen. Increasing cell density had a marked effect on the testosterone production rate per 105 cells, and the stimulatory effect of IGFs was only seen at relatively high cell density (2.8 × 105 cells/ml). Varying the period of pre-incubation with IGFs between 0.5 and 16 h, it was found that a 1-h period gave maximal stimulation. We conclude that a short exposure to IGFs is capable of increasing hCG-stimulated steroidogenesis in Leydig cells, and postulate that this effect may be part of an intratesticular paracrine control mechanism.


Sign in / Sign up

Export Citation Format

Share Document