Tyrosine kinase receptor alteration of renal vasoconstriction in rats is sex- and age-related

2012 ◽  
Vol 90 (10) ◽  
pp. 1372-1379 ◽  
Author(s):  
John C. Passmore ◽  
John T. Fleming ◽  
Suresh C. Tyagi ◽  
Jeff C. Falcone
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Young Male ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Tyrosine Kinase Receptor ◽  
Middle Aged ◽  
Male And Female Rats ◽  
Age Related

Male rat renal blood vessels undergo reduced contraction to norepinephrine with aging. There is a greater renal vascular impairment in male compared with female rats. We investigated specific tyrosine kinase receptor inhibition of renal interlobar artery responsiveness to phenylephrine in male and female rats at specifically designated ages. Vessels from young male rats contracted much less to phenylephrine when the vessels were pretreated with the tyrosine kinase inhibitors Lavendustin A, HNMPA-(AM)3, or AG1478. Vessels from adult female rats pretreated with Lavendustin A showed no difference in contraction from control, but did demonstrate a slightly reduced contraction when pretreated with AG1478. Middle-aged male rat vessels treated with Lavendustin A demonstrated no inhibition, but the insulin and epidermal growth factor receptor (EGFR) antagonists both induced a decline in contraction. Vessels from aged male rats demonstrated no effect related to the 3 pretreatments. Middle-aged and aged female rats pretreated with any inhibitor demonstrated no inhibitor-dependent alterations. We conclude that maximum contraction of interlobar arteries from adult male rats is reduced when tyrosine kinase receptor activity is reduced. Female rats demonstrated much less inhibitor-related change of contraction.

Effects of trenbolone acetate and testosterone on growth and on plasma concentrations of corticosterone and ACTH in rats

1990 ◽  
Vol 126 (3) ◽  
pp. 461-466 ◽  
Author(s):  
M. N. Sillence ◽  
R. G. Rodway
Keyword(s):  
Weight Gain ◽  
Growth Response ◽  
Plasma Concentrations ◽  
Female Rats ◽  
Male Rats ◽  
Adrenal Weight ◽  
Trenbolone Acetate ◽  
Male And Female Rats ◽  
Age Related ◽  
Old Rats

ABSTRACT The effects of trenbolone acetate (TBA) on growth and on plasma concentrations of corticosterone were examined in male and female rats. At 5 weeks of age, rats were injected with TBA (0·8 mg/kg) dissolved in peanut oil, or with oil alone, daily for 10 days. In female rats, TBA caused an increase in weight gain (20–38%), a reduction in adrenal weight (19%) and a reduction in plasma concentrations of corticosterone (55%). In contrast, TBA-treated male rats showed no significant increase in weight gain, no significant change in adrenal weight and no reduction in plasma concentrations of corticosterone. The mechanism by which adrenal activity was suppressed in TBA-treated female rats was examined and the response compared with that to testosterone. Female rats (8 weeks old) were injected daily either with oil vehicle, TBA (0·8 mg/kg) or testosterone propionate (0·8 mg/kg). Testosterone increased weight gain (24%), but the growth response to TBA treatment was significantly greater (97%). A reduction in plasma concentrations of corticosterone (45%) was again observed in response to TBA. However, testosterone increased plasma concentrations of corticosterone (52%) above those of control values. Neither androgen affected plasma concentrations of ACTH. Finally, the effects of TBA were examined in 6-week-old female rats, to characterize further the apparent age-related increase in responsiveness. The growth response of 6-week-old rats (60–74%) was intermediate between that seen in 5- and 8-week-old animals. It is concluded that part of the anabolic activity of TBA may be related to a reduction in circulating concentrations of corticosterone. The effect of TBA on corticosterone concentrations differs from that of the natural androgen, testosterone, and does not appear to be mediated by a reduction in plasma concentrations of ACTH. Journal of Endocrinology (1990) 126, 461–466

scholarly journals Developmental increases in plasma leptin binding activity and tissue Ob-Re mRNA expression in the rat

2005 ◽  
Vol 184 (3) ◽  
pp. 535-541 ◽  
Author(s):  
Jeremy T Smith ◽  
Peter J Mark ◽  
Brendan J Waddell
Keyword(s):  
Mrna Expression ◽  
Adult Life ◽  
Tissue Expression ◽  
Binding Activity ◽  
Female Rats ◽  
Male Rats ◽  
Target Cells ◽  
Male And Female Rats ◽  
Age Related ◽  
Plasma Leptin

Leptin’s actions are mediated via the long form of its receptor, Ob-Rb, but access to this receptor on target cells is also influenced by truncated leptin receptor isoforms Ob-Ra and Ob-Re. Plasma leptin binding activity is primarily attributed to Ob-Re, which can restrict leptin passage to extravascular tissue. In this study we investigated whether plasma leptin binding activity changes from fetal to adult life in male and female rats, and whether tissue expression of Ob-Re mRNA changes during development. Plasma leptin binding activity was low in the fetus and prepubertal rats but then increased in male rats by more than three-fold from pre- to post-puberty and by a further two-fold by 7 months of age. A more modest increase in plasma leptin binding activity was observed in females such that a clear sex difference became evident after puberty. There was also a reduction in hypothalamic Ob-Rb protein content between puberty and adult life in female rats. Combined with the higher levels of plasma leptin binding activity, this change in hypothalamic Ob-Rb expression is likely to lead to a more leptin-resistant state in aging females. To assess possible sources of circulating leptin binding activity, Ob-Re mRNA expression was measured by quantitative RT-PCR in several tissues from male rats soon after puberty and at 7 months of age. All tissues examined (testis, epididymis, adrenal, liver, adipose and spleen) expressed Ob-Re mRNA, and there was a dramatic, age-related increase in expression (> 300-fold) in the spleen. These data show that, in addition to the developmental increase in hypothalamic Ob-Rb expression previously reported, plasma leptin binding activity increases several fold from fetal to adult life in the rat. This suggests that the actions of leptin depend not only on its synthesis in adipose tissue and Ob-Rb expression in target cells, but also on factors that regulate tissue expression of Ob-Re and thus leptin transport within plasma.

scholarly journals Gender and Puberty Interact on the Stress-Induced Activation of Parvocellular Neurosecretory Neurons and Corticotropin-Releasing Hormone Messenger Ribonucleic Acid Expression in the Rat

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 137-146 ◽  
Author(s):  
Victor Viau ◽  
Brenda Bingham ◽  
Jennifer Davis ◽  
Patricia Lee ◽  
Margaret Wong
Keyword(s):  
Paraventricular Nucleus ◽  
Cell Types ◽  
Female Rats ◽  
Male Rats ◽  
Messenger Ribonucleic Acid ◽  
Fos Protein ◽  
Male And Female Rats ◽  
Age Related ◽  
And Gender ◽  
Hpa Function

Individual variations in hypothalamic-pituitary-adrenal (HPA) function are most evident at or beyond the time of puberty, when marked changes in sex steroid release occur. To explore the nature by which gender differences in HPA function emerge we examined in prepubertal (∼30-d-old) and postpubertal (∼60-d-old) male and female rats HPA activity under basal conditions and in response to 30 min of restraint. Within the ACTH-regulating, medial parvocellular portion of the paraventricular nucleus, restraint-induced Fos protein and arginine vasopressin heteronuclear RNA were lower in 60- than in 30-d-old males. No such age-related shift in the response of these synaptic and transcriptional markers of cellular activation occurred in female rats. Basal CRH mRNA expression levels in the paraventricular nucleus increased with age in female but not male rats. Conversely, only male rats showed an age-related increase in basal CRH mRNA in the central amygdala, suggesting that neuronal and neurosecretory CRH-expressing cell types are subject to different pubertal and gender influences. We conclude that gonadal regulation of the HPA axis develops via distinct mechanisms in males and females. Puberty-related shifts in parvocellular neurosecretory function in males are emphasized by stress-induced shifts in neuronal activation, whereas biosynthetic alterations dominate in female rats.

scholarly journals Age-associated changes in excitation-contraction coupling are more prominent in ventricular myocytes from male rats than in myocytes from female rats

2010 ◽  
Vol 298 (2) ◽  
pp. H659-H670 ◽  
Author(s):  
Susan E. Howlett
Keyword(s):  
Sex Differences ◽  
Ventricular Myocytes ◽  
Contractile Function ◽  
Pulse Frequency ◽  
Female Rats ◽  
Male Rats ◽  
Cardiac Contractile Function ◽  
Ec Coupling ◽  
Male And Female Rats ◽  
Age Related

We evaluated effects of age on components of excitation-contraction (EC) coupling in ventricular myocytes from male and female rats to examine sex differences in mechanisms responsible for age-related contractile dysfunction. Myocytes were isolated from anesthetized young adult (∼3 mo) and aged (∼24 mo) Fischer 344 rats. Ca2+ concentrations and contractions were measured simultaneously (37°C, 2 Hz). Fractional shortening declined with age in males (6.7 ± 0.6% to 2.4 ± 0.4%; P < 0.05), as did peak Ca2+ transients (47.7 ± 4.6 to 28.1 ± 2.1 nM; P < 0.05) and Ca2+ current densities (−7.7 ± 0.7 to −6.2 ± 0.5 pA/pF; P < 0.05). Although sarcoplasmic reticulum (SR) Ca2+ content was similar regardless of age in males, EC coupling gain declined significantly with age to 55.8 ± 7.8% of values in younger males. In contrast with results in males, contraction and Ca2+ transient amplitudes were unaffected by age in females. Ca2+ current density declined with age in females (−7.5 ± 0.5 to −5.1 ± 0.7 pA/pF; P < 0.05), but SR Ca2+ content actually increased dramatically (49.0 ± 7.5 to 147.3 ± 28.5 nM; P < 0.05). Even so, EC coupling gain was not affected by age in female myocytes. Age also promoted hypertrophy of male myocytes more than female myocytes. Age and sex differences in EC coupling were largely maintained when conditioning pulse frequency was increased to 4 Hz. Contractions, Ca2+ transients, and EC coupling gain were also smaller in young females than in young males. Thus age-dependent changes are more prominent in myocytes from males than females. Increased SR Ca2+ content may compensate for reduced Ca2+ current to preserve contractile function in aged females, which may limit the detrimental effects of age on cardiac contractile function.

scholarly journals Androgens enhance adult hippocampal neurogenesis in males but not females in an age-dependent manner

2019 ◽  
Author(s):  
Paula Duarte-Guterman ◽  
Dwayne K. Hamson ◽  
Steven R. Wainwright ◽  
Carmen Chow ◽  
Jessica Chaiton ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Female Rats ◽  
Male Rats ◽  
Dependent Manner ◽  
Middle Aged ◽  
Young Males ◽  
Neuron Survival ◽  
Male And Female Rats ◽  
Age Dependent

AbstractAndrogens (testosterone and dihydrotestosterone) increase adult hippocampal neurogenesis by increasing new neuron survival in male rats and mice via an androgen receptor pathway, but it is not known whether androgens regulate neurogenesis in females and whether the effect is age-dependent. We investigated the effects of dihydrotestosterone, a potent androgen, on neurogenesis in adult and middle-aged males and females. Rats were gonadectomized and injected with the DNA synthesis marker, bromodeoxyuridine (BrdU). The following day rats began receiving daily injections of oil or DHT for 30 days. We evaluated cell proliferation (Ki67) and new neuron survival (BrdU and BrdU/NeuN) in the hippocampus of male and female rats using immunohistochemistry. As expected, DHT increased new neuron survival in young males but surprisingly not in middle-aged male rats. In females, DHT did not significantly affect adult neurogenesis in young or middle age. Our results indicate that DHT regulates adult hippocampal neurogenesis in a sex- and age-dependent manner.

Aging and fluid homeostasis in rats

1997 ◽  
Vol 273 (4) ◽  
pp. R1441-R1450 ◽  
Author(s):  
Neil E. Rowland ◽  
Annie Morien ◽  
Mircea Garcea ◽  
Melvin J. Fregly
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Acute Administration ◽  
Salt Appetite ◽  
Sprague Dawley ◽  
Cross Sectional ◽  
Aging Rats ◽  
Fluid Homeostasis ◽  
Male And Female Rats ◽  
Age Related

The capacity of aging rats to defend body fluid homeostasis in response to a variety of dipsogenic and natriorexigenic stimuli was assessed. Male and female rats of both the Fischer 344 (FR) and Sprague-Dawley (SD) strains were used and tested at target ages of ∼5, 10, 15, and 20 mo in both longitudinal and cross-sectional studies. There were no consistent age-related declines in water intake in response to water deprivation or acute administration of hypertonic NaCl; angiotensin (ANG) I, II, III; or isoproterenol. Likewise, there were no major impairments in either urinary excretion of the hypertonic NaCl load or excretion of water or hypotonic NaCl loads, although the latter were excreted more slowly in the older cohorts. The preference/aversion functions for NaCl solutions differed between SD and FR rats, but did not change with age except in male FR rats that lost their aversion to dilute NaCl at 20 mo of age. Intake of hypotonic NaCl solution after acute sodium depletion (furosemide treatment) showed a partial decline with age, and the older rats sustained larger estimated sodium deficits after a 6-h repletion period. A more complete age-related decline was observed in the intake of hypertonic NaCl stimulated by chronic dietary administration of a kininase II inhibitor (ramipril). Male rats of 15–20 mo of age showed no ramipril-induced sodium appetite. Brain ANG II receptor density, determined by autoradiography, declined by almost 50% in the paraventricular nucleus at 20 mo of age and declined slightly in the organum vasculosum laminae terminalis but did not decline in either the supraoptic nucleus or subfornical organ. Thus the major deficits in fluid intake in aging rats are related to salt appetite; the mechanism was not identified definitively.

scholarly journals Differential expression of gonadotropin and prolactin antigens by GHRH target cells from male and female rats

1999 ◽  
Vol 162 (2) ◽  
pp. 177-187 ◽  
Author(s):  
GV Childs ◽  
G Unabia ◽  
BT Miller ◽  
TJ Collins
Keyword(s):  
Secretory Activity ◽  
Fold Increase ◽  
Pituitary Hormones ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Target Cells ◽  
Pituitary Cells ◽  
Male And Female Rats ◽  
In Cells

There is a 2- to 3-fold increase in luteinizing hormone-beta (LHbeta) or follicle-stimulating hormone-beta (FSHbeta) antigen-bearing gonadotropes during diestrus in preparation for the peak LH or FSH secretory activity. This coincides with an increase in cells bearing LHbeta or FSHbeta mRNA. Similarly, there is a 3- to 4-fold increase in the percentage of cells that bind GnRH. In 1994, we reported that this augmentation in gonadotropes may come partially from subsets of somatotropes that transitionally express LHbeta or FSHbeta mRNA and GnRH-binding sites. The next phase of the study focused on questions relating to the somatotropes themselves. Do these putative somatogonadotropes retain a somatotrope phenotype? As a part of ongoing studies that address this question, a biotinylated analog of GHRH was produced, separated by HPLC and characterized for its ability to elicit the release of GH as well as bind to pituitary target cells. The biotinylated analog (Bio-GHRH) was detected cytochemically by the avidin-peroxidase complex technique. It could be displaced by competition with 100-1000 nM GHRH but not corticotropin-releasing hormone or GnRH. In cells from male rats exposed to 1 nM Bio-GHRH, 28+/-6% (mean+/-s.d) of pituitary cells exhibited label for Bio-GHRH (compared with 0.8+/-0.6% in the controls). There were no differences in percentages of GHRH target cells in populations from proestrous (28+/-5%) and estrous (25+/-5%) rats. Maximal percentages of labeled cells were seen following addition of 1 nM analog for 10 min. In dual-labeled fields, GHRH target cells contained all major pituitary hormones, but their expression of ACTH and TRH was very low (less than 3% of the pituitary cell population) and the expression of prolactin (PRL) and gonadotropins varied with the sex and stage of the animal. In all experimental groups, 78-80% of Bio-GHRH-reactive cells contained GH (80-91% of GH cells). In male rats, 33+/-6% of GHRH target cells contained PRL (37+/-9% of PRL cells) and less than 20% of these GHRH-receptive cells contained gonadotropins (23+/-1% of LH and 31+/-9% of FSH cells). In contrast, expression of PRL and gonadotropins was found in over half of the GHRH target cells from proestrous female rats (55+/-10% contained PRL; 56+/-8% contained FSHbeta; and 66+/-1% contained LHbeta). This reflected GHRH binding by 71+/-2% PRL cells, 85+/-5% of LH cells and 83+/-9% of FSH cells. In estrous female rats, the hormonal storage patterns in GHRH target cells were similar to those in the male rat. Because the overall percentages of cells with Bio-GHRH or GH label do not vary among the three groups, the differences seen in the proestrous group reflect internal changes within a single group of somatotropes that retain their GHRH receptor phenotype. Hence, these data correlate with earlier findings that showed that somatotropes may be converted to transitional gonadotropes just before proestrus secretory activity. The LH and FSH antigen content of the GHRH target cells from proestrous rats demonstrates that the LHbeta and FSHbeta mRNAs are indeed translated. Furthermore, the increased expression of PRL antigens by these cells signifies that these convertible somatotropes may also be somatomammotropes.

Comparison of creatinine and inulin clearances in male and female rats

1965 ◽  
Vol 209 (4) ◽  
pp. 849-852 ◽  
Author(s):  
Alice M. Harvey ◽  
Richard L. Malvin
Keyword(s):  
High Plasma ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Control Male ◽  
Male And Female ◽  
Intramuscular Dose ◽  
Ureteral Catheterization ◽  
Arterial Blood ◽  
Male And Female Rats

Creatinine and inulin clearances were compared in anesthetized male and female rats. Continuous intravenous infusion, midpoint arterial blood sampling, and ureteral catheterization aided accurate measurements. Average inulin clearances were 1.0 ml/min per 100 g. In the control male rat the creatinine clearance persistently exceeded that of inulin. The elevated CCr: CIn ratio could be reduced to 1 by probenecid, PAH, mercury, or high plasma levels of creatinine. In females a single intramuscular dose of testosterone elevated the ratio to that seen in male rats. This effect declined within 6 hr. Manipulations with steroids other than testosterone did not affect results in either sex. It is suggested that male rats secrete creatinine under the influence of androgens and that inulin is therefore a better measurement of the glomerular filtration rate in the male rat.

Effect of benzo(a)pyrene on the expression of AhR-regulated microRNA in female and male rat lungs

2020 ◽  
Vol 66 (3) ◽  
pp. 224-232
Author(s):  
S.V. Filippov ◽  
A.A. Yarushkin ◽  
A.K. Yakovleva ◽  
V.V. Kozlov ◽  
L.F. Gulyaeva
Keyword(s):  
Lung Cancer ◽  
Target Genes ◽  
In Silico Analysis ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Epigenetic Effects ◽  
Rat Lungs ◽  
Male And Female Rats ◽  
Mirnas Expression

Smoking is the main risk factor for lung cancer, mainly due to presence of nitrosamines and polycyclic aromatic hydrocarbons, including benzo[a]pyrene (BP) in tobacco smoke composition. The genotoxic effect of BP is based on the high DNA-binding ability of its metabolites, while the epigenetic effects are mediated by a change in the expression of cancer related genes or regulatory RNAs. It has been shown that women have a higher risk to develop lung cancer upon smoking rather than men. We hypothesized that crosstalk between signaling pathways activated by BP and estrogens could underlie the sex-dependent differences in miRNAs expression. To test this hypothesis, male and female rats were subjected to short-term or long-term BP exposure. Using in silico analysis, miRNAs containing the ER- and AhR-binding sites in the promoters of the genes (or host genes) were selected. During chronic exposure of BP the expression of miR-22-3p, -29a-3p, -126a-3p, -193b-5p in the lungs of male rats were significantly increased, while the level of miRNA-483-3p were decreased. Expression of miRNA-483-3p was up-regulated during chronic BP exposure in the lungs of female rats and the levels of other studied miRNAs were unchanged. In turn, changes in the expression of miRNAs were followed by changes in the expression of their target genes, including PTEN, EMP2, IGF1, ITGA6, SLC34A2, and the observed changes in female and male rat lungs were varied. Thus, our results suggest that sex-dependent epigenetic effects of BP may be based on different expression of AhR- and ER- regulated miRNAs.

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