Insulin sensitivity, leptin, adiponectin, resistin, and testosterone in adult male and female rats after maternal-neonatal separation and environmental stress

2018 ◽  
Vol 314 (1) ◽  
pp. R12-R21 ◽  
Author(s):  
Hershel Raff ◽  
Brian Hoeynck ◽  
Mack Jablonski ◽  
Cole Leonovicz ◽  
Jonathan M. Phillips ◽  
...  

Care of premature infants often requires parental and caregiver separation, particularly during hypoxic and hypothermic episodes. We have established a neonatal rat model of human prematurity involving maternal-neonatal separation and hypoxia with spontaneous hypothermia prevented by external heat. Adults previously exposed to these neonatal stressors show a sex difference in the insulin and glucose response to arginine stimulation suggesting a state of insulin resistance. The current study used this cohort of adult rats to evaluate insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)], plasma adipokines (reflecting insulin resistance states), and testosterone. The major findings were that daily maternal-neonatal separation led to an increase in body weight and HOMA-IR in adult male and female rats and increased plasma leptin in adult male rats only; neither prior neonatal hypoxia (without or with body temperature control) nor neonatal hypothermia altered subsequent adult HOMA-IR or plasma adiponectin. Adult male-female differences in plasma leptin were lost with prior exposure to neonatal hypoxia or hypothermia; male-female differences in resistin were lost in the adults that were exposed to hypoxia and spontaneous hypothermia as neonates. Exposure of neonates to daily hypoxia without spontaneous hypothermia led to a decrease in plasma testosterone in adult male rats. We conclude that neonatal stressors result in subsequent adult sex-dependent increases in insulin resistance and adipokines and that our rat model of prematurity with hypoxia without hypothermia alters adult testosterone dynamics.

2013 ◽  
pp. S99-S108 ◽  
Author(s):  
R. ŠLAMBEROVÁ ◽  
E. MACÚCHOVÁ ◽  
K. NOHEJLOVÁ-DEYKUN ◽  
B. SCHUTOVÁ ◽  
L. HRUBÁ ◽  
...  

The aim of the present study was to compare the response to acute application of several drugs in adult male and female rats prenatally exposed to methamphetamine (MA). Spontaneous locomotor activity and exploratory behavior of adult male and female rats prenatally exposed to MA (5 mg/kg) or saline were tested in a Laboras apparatus (Metris B.V., Netherlands) for 1 h. Challenge dose of the examined drug [amphetamine – 5 mg/kg; cocaine – 5mg/kg; MDMA (3,4-methylenedioxymethamphetamine) – 5 mg/kg; morphine – 5 mg/kg; THC (delta9-tetrahydrocannabinol) – 2 mg/kg] or saline was injected prior to testing. Our data demonstrate that prenatal MA exposure did not affect behavior in male rats with cocaine or morphine treatment, but increased locomotion and exploration in females. Application of amphetamine and MDMA in adulthood increased activity in both sexes, while cocaine and THC only in female rats. Morphine, on the other hand, decreased the activity in the Laboras test in both sexes. As far as sex and estrous cycle is concerned, the present study shows that males were generally less active than females and also females in proestrus-estrus phase of the estrous cycle were more active than females in diestrus. In conclusion, the present study shows that the prenatal MA exposure does not induce general sensitization but affects the sensitivity to drugs dependently to mechanism of drug action and with respect to gonadal hormones.


2014 ◽  
Vol 115 (1-2) ◽  
pp. 43-59 ◽  
Author(s):  
Romana Šlamberová ◽  
Eva Macúchová ◽  
Kateryna Nohejlová ◽  
Andrea Štofková ◽  
Jana Jurčovičová

The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to adult amphetamine (AMP) treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed) were administered with AMP (5 mg/kg) or saline (1 ml/kg) in adulthood. Behaviour in unknown environment was examined in open field test (Laboras), active drug-seeking behaviour in conditioned place preference test (CPP), spatial memory in the Morris water maze (MWM), and levels of corticosterone (CORT) were analyzed by enzyme immunoassay (EIA). Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled) regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing) only in prenatally MA-exposed animals. AMP induced sensitization only in male rats, but not in females when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM test, AMP worsened the performance only in females, but not in males. On the other hand, males swam faster after chronic AMP treatment regardless of the prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in females in all measurement settings. In males, prenatal MA exposure and chronic adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult AMP treatment affects behaviour of adult rats, their spatial memory and stress response in sex-specific manner. The effect is also influenced by prenatal drug exposure.


2002 ◽  
Vol 283 (2) ◽  
pp. H562-H567 ◽  
Author(s):  
Denise M. Galipeau ◽  
Linfu Yao ◽  
John H. McNeill

Hyperinsulinemia and insulin resistance have been linked to hypertension; however, the influence of sex on this relationship has not been well studied. The purpose of this experiment was to compare the effects of chronic insulin treatment on insulin sensitivity and blood pressure in male and female rats. Male and female Wistar rats were treated with insulin (2 U/day) via subcutaneous sustained release implants for 5 wk. Systolic blood pressure was measured via the tail-cuff method before and after treatment, and insulin sensitivity was assessed with an oral glucose tolerance test. The insulin sensitivity of female rats was 4.5-fold greater than male rats. Chronic insulin treatment impaired insulin sensitivity in both sexes; however, this occurred to a greater degree in male rats. Blood pressure increased in male rats treated with insulin only. The results demonstrate that hyperinsulinemia and insulin resistance are associated with hypertension in male rats only. Therefore, the link between these conditions appears to depend on sex.


1984 ◽  
Vol 101 (1) ◽  
pp. 87-NP ◽  
Author(s):  
M. O. Dada ◽  
G. T. Campbell ◽  
C. A. Blake

ABSTRACT We analysed cell types in the pars distalis of normal young adult male and female rats with respect to their percentages and the relative volumes they occupy. In male rats the percentages of the cell types were: prolactin 49·80, GH 22·67, LH 5·04, FSH 4·22, ACTH 2·93 and TSH 2·09, The volume densities were: prolactin 20·48, GH 20·95, LH 7·34, FSH 6·73, ACTH 3·75 and TSH 3·19. In female rats the percentages of the cell types were: prolactin 52·40, GH 20·30, LH 5·89, FSH 4·06, ACTH 2·53, TSH 2·40 and the volume densities were: prolactin 28·09, GH 20·86, LH 8·11, FSH 5·46, ACTH 3·49 and TSH 2·91. The percentages of pars distalis cells which did not stain with the antisera to the six classical hormones were 17·47 in male and 16·48 in female rats. The results suggest that (1) in both sexes the number (N) of prolactin cells > N of GH cells > N of gonadotrophs > N of TSH or ACTH cells, (2) the percentage of each cell type was similar in both sexes, (3) the volume density (Vv) of prolactin cells was greater than the Vv of GH cells in female but not in male rats and in both sexes the Vv of GH cells > the Vv of gonadotrophs > the Vv of TSH or ACTH cells, (4) in both sexes the volume (V) of prolactin cells < the V of GH cells < the V of gonadotrophs, the V of TSH cells or the V of ACTH cells, (5) the V of prolactin cells was greater in female than in male rats and (6) approximately 17% of the cells in the pars distalis of both sexes did not contain 'immunoreactive' prolactin, GH, LH, FSH, TSH or ACTH. J. Endocr. (1984) 101, 87–94


Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2689-2699 ◽  
Author(s):  
A. C. Kentner ◽  
S. A. McLeod ◽  
E. F. Field ◽  
Q. J. Pittman

Inflammatory molecules, such as cyclooxygenase (COX), a prostaglandin synthetic enzyme, have been identified as a marker of depressive symptomology. Previously, we have observed elevated basal COX-2 expression in the hypothalamus of adult male rats treated neonatally with lipopolysaccharide (LPS), which might suggest a phenotype for disrupted hedonic behavior, a symptom of depression. However, COX-2 and its contribution to the expression of anhedonic behavior has not been investigated in these males or in female rats across the estrous cycle, which is the purpose of the current work. Here, we examine the effects of a neonatal LPS challenge or saline on the sucrose preference test as a measure of anhedonia, and hypothalamic COX-2 expression, in adult male and freely cycling female rats. Our data indicate a sex difference in that neonatal LPS at postnatal d 14 causes elevated basal expression of hypothalamic COX-2 in male, but not in female, rats. Additionally, baseline sucrose preference in male and female rats was unaltered as a function of neonatal LPS treatment or estrous cycle stage. In both male and female animals, 50 μg/kg LPS in adulthood caused elevated plasma IL-6 and hypothalamic COX-2 expression in neonatally saline-treated rats but significantly less so in neonatally LPS-treated rats of both sexes; this neonatal programming was not evident for sucrose preference or for total fluid intake (even after much higher doses of LPS). Our data are suggestive of a dissociation between inflammation and anhedonic behavior and a differential effect of neonatal inflammation in males and females.


1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Song ◽  
Fang Yuan ◽  
Xiaohong Li ◽  
Xipeng Ma ◽  
Xinmin Yin ◽  
...  

Abstract Background Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the USA. Dietary copper-fructose interactions alter gut microbial activity and contribute to the development of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine whether dietary copper-fructose interactions alter gut microbial activity in a sex-differential manner and whether sex differences in gut microbial activity are associated with sex differences in hepatic steatosis. Methods Male and female weanling Sprague-Dawley (SD) rats were fed ad libitum with an AIN-93G purified rodent diet with defined copper content for 8 weeks. The copper content is 6 mg/kg and 1.5 mg/kg in adequate copper diet (CuA) and marginal copper diet (CuM), respectively. Animals had free access to either deionized water or deionized water containing 10% fructose (F) (w/v) as the only drink during the experiment. Body weight, calorie intake, plasma alanine aminotransferase, aspartate aminotransferase, and liver histology as well as liver triglyceride were evaluated. Fecal microbial contents were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Fecal and cecal short-chain fatty acids (SCFAs) were determined by gas chromatography-mass spectrometry (GC-MS). Results Male and female rats exhibit similar trends of changes in the body weight gain and calorie intake in response to dietary copper and fructose, with a generally higher level in male rats. Several female rats in the CuAF group developed mild steatosis, while no obvious steatosis was observed in male rats fed with CuAF or CuMF diets. Fecal 16S rRNA sequencing analysis revealed distinct alterations of the gut microbiome in male and female rats. Linear discriminant analysis (LDA) effect size (LEfSe) identified sex-specific abundant taxa in different groups. Further, total SCFAs, as well as, butyrate were decreased in a more pronounced manner in female CuMF rats than in male rats. Of note, the decreased SCFAs are concomitant with the reduced SCFA producers, but not correlated to hepatic steatosis. Conclusions Our data demonstrated sex differences in the alterations of gut microbial abundance, activities, and hepatic steatosis in response to dietary copper-fructose interaction in rats. The correlation between sex differences in metabolic phenotypes and alterations of gut microbial activities remains elusive.


2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.


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