Evaluation of thyroid function in neonatal and adult rats: The neglected endocrine mode of action

2003 ◽  
Vol 75 (11-12) ◽  
pp. 2055-2068 ◽  
Author(s):  
M. S. Christian ◽  
N. A. Trenton

Although known to regulate growth and development, cellular metabolism, the use of oxygen, and basal metabolic rate, thyroid hormones have been only minimally evaluated in neonatal rodents at critical times of development. Despite some modulation of metabolic rate by other hormones, such as testosterone, growth hormone, and norepinephrine, 3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4) are the most important metabolic rate modulators. Endpoints used for thyroid function assessment in neonatal and adult rats include thyroid-stimulating hormone (TSH), T3, and T4 levels and histopathology. In rodents, decreased serum levels of T3 and T4 and increased serum TSH levels, with sustained release of TSH and resultant follicular cell hypertrophy/hyperplasia, are typical hormonal and histopathological findings attributable to compounds altering thyroid function. Hypothyroidism early in the neonatal period can affect reproductive endpoints in both male and female rats, with the critical period of exposure being the first two weeks postnatal. Hypothyroidism has been shown to reduce gonadotrophin levels and delay pubertal spermatogenesis in male rats and to block gonadotropin-induced first ovulation in immature female rats by decreasing FSH and luteinizing hormone (LH) serum concentrations. Inclusion of evaluations of TSH, T3, and T4 assays in multigeneration and developmental neurotoxicity protocols may assist in risk assessments.

1989 ◽  
Vol 120 (2) ◽  
pp. 261-268 ◽  
Author(s):  
A. Kooy ◽  
R. F. A. Weber ◽  
M. P. Ooms ◽  
J. T. M. Vreeburg

ABSTRACT The effects of the transplantable purely prolactin-secreting tumour 7315b on serum gonadotrophins were studied in adult rats. Possible contributions of the adrenals to the tumour-induced inhibition of serum LH and FSH were evaluated. The suppressive actions of tumour 7315b on serum gonadotrophins in gonadectomized plus adrenalectomized male and female rats were compared. Within 4 weeks after inoculation of tumour 7315b in intact male rats very high levels of prolactin and decreased serum levels of gonadotrophins and testosterone were recorded. At autopsy reduced weights of testes and accessory sex organs and slightly increased adrenal weights were found. In addition, in animals treated with a small testosterone-filled capsule after castration, tumour 7315b reduced serum concentrations of LH and FSH. Adrenalectomy did not prevent this suppressive action of the tumour on the post-castration rise of serum gonadotrophins. Suppression of serum gonadotrophins during hyperprolactinaemia was greater in gonadectomized plus adrenalectomized female rats than in male rats, indicating that the degree of the tumour-induced suppression of LH and FSH after castration is determined to a large extent by the sex of the animal. The purely prolactin-secreting tumour 7315b has therefore been shown to be a suitable model for studying the effects of severe hyperprolactinaemia on the pituitary-gonadal axis in rats. Journal of Endocrinology (1989) 120, 261–268


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 2021 ◽  
pp. 1-9
Author(s):  
Mohammad-Sedigh Khosravi ◽  
Alireza Samimiat ◽  
Bahar Mazaheri ◽  
Farzaneh Ashrafi ◽  
Ardeshir Talebi ◽  
...  

Backgrounds. Cisplatin (CP) still is a novel choice for solid tumor therapy, but it is accompanied with the side effect of nephrotoxicity. Hydration may reduce the risk of CP-induced nephrotoxicity, while the issue is still challenging. In this study, five types of hydration protocols including saline, mannitol, dextrose saline, saline plus furosemide, and saline plus mannitol were examined in both sexes of rats during CP therapy. Methods. Seventy-six male and female Wistar rats in 14 groups of experiments were subjected to CP therapy, and five types of hydration protocols were implemented, and the induced nephrotoxicity was evaluated via biochemical markers, kidney function parameters, and pathology investigation. Results. Male and female rats had different responses to hydration protocol types. The higher mortality rate was seen in female rats that received mannitol or dextrose hydration types. In addition, the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and sodium excretion fraction (ENa%) increased and the clearance of Cr (ClCr) decreased significantly ( P < 0.05 ) in female rats hydrated with saline plus furosemide or mannitol plus saline-treated groups. The worsened condition in male rats is observed in the mannitol hydration group with a significant decrease of ClCr and significant increase of serum BUN and Cr and ENa% ( P < 0.05 ). The higher kidney tissue damage score (KTDS) in the mentioned groups verified the findings. Conclusion. Hydration with mannitol or dextrose promotes the risk of nephrotoxicity during CP therapy with more intensity on the female.


1976 ◽  
Vol 71 (1) ◽  
pp. 109-114 ◽  
Author(s):  
I. DONIACH ◽  
D. J. SHALE

SUMMARY From the differences in radiation profiles between 131I and 125I isotopes of iodine it would be expected that they would show different effects on thyroid function. The differences should lead to lower rates of thyroid gland destruction with 125I and hence less post-irradiation hypothyroidism. This difference in biological effect has been demonstrated in rats by indirect assessment of thyroid function. In this report the long-term effects of a range of similar doses of 131I and 125I were compared, in male and female rats, by direct assessment of thyroid function. Seventeen months after receiving 25 and 125 μCi of 131I, male and female rats showed significant elevation of serum TSH concentration and a reduction in 3 h radioiodine uptake. Rats receiving 1 and 5 μCi of 131I and all doses of 125I showed no significant changes in thyroid function. These findings confirm the previously reported differences in effect between the 131I and 125I isotopes of iodine in the rat.


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.


1980 ◽  
Vol 86 (1) ◽  
pp. 79-92 ◽  
Author(s):  
W. P. HERMANS ◽  
E. C. M. VAN LEEUWEN ◽  
M. H. M. DEBETS ◽  
F. H. DE JONG

Administration of steroid-free bovine follicular fluid (bFF), containing inhibin-like activity, depressed levels of FSH measured 4 h after injection in intact adult and 35-day-old female rats, but not in younger females. Suppression of FSH was also observed in intact male rats, aged 55 days, but not in older and younger male rats. Eight hours after injection of bFF, FSH levels were depressed in 15-day-old and older immature and adult rats of both sexes. Male and female rats, gonadectomized 2 days earlier, responded similarly to bFF treatment as did the intact animals. In a second experiment it was found that the rise of FSH levels, occurring within 8 h of gonadectomy, decreased with age in male and increased with age in female rats. Steroid treatment was found to prevent the rise in FSH levels partially in 15-day-old male and completely in 25-day-old female rats, whereas treatment with bFF was fully effective in blocking the FSH rise in both immature and adult rats of both sexes. It is concluded that inhibin might be a major physiological factor in a fast-acting control of FSH concentrations from at least the age of 25 days onwards in female rats. In male rats its physiological significance might be limited to the prepubertal period, despite the fact that pituitary secretion of FSH is suppressed by exogenous inhibin-like activity at all ages studied.


2011 ◽  
Vol 301 (5) ◽  
pp. L804-L811 ◽  
Author(s):  
Edgar E. Kooijman ◽  
Stephanie R. Kuzenko ◽  
Denghuang Gong ◽  
Michael D. Best ◽  
Hans G. Folkesson

Cell membrane phospholipids, like phosphatidylinositol 4,5-bisphosphate [PI( 4 , 5 )P2], can regulate epithelial Na channel (ENaC) activity. Gender differences in lung ENaC expression have also been demonstrated. However, the effects in vivo on alveolar fluid clearance are uncertain. Thus PI( 4 , 5 )P2 effects on alveolar fluid clearance were studied in male and female rats. An isosmolar 5% albumin solution was intrapulmonary instilled; alveolar fluid clearance was studied for 1 h. Female rats had a 37 ± 19% higher baseline alveolar fluid clearance than male rats. Bilateral ovariectomy attenuated this gender difference. Compared with controls, PI( 4 , 5 )P2 instillation (300 μM) increased alveolar fluid clearance by ∼93% in both genders. Amiloride or the specific αENaC small-interfering RNA inhibited baseline and PI( 4 , 5 )P2-stimulated alveolar fluid clearance in both genders, indicating a dependence on amiloride-sensitive pathways. The fraction of amiloride inhibition was greater in PI( 4 , 5 )P2-instilled rats (male: 64 ± 10%; female: 70 ± 11%) than in controls (male: 30 ± 6%; female: 44 ± 8%). PI( 4 , 5 )P2 instillation lacked additional alveolar fluid clearance stimulation above that of terbutaline, nor did propranolol inhibit alveolar fluid clearance after PI( 4 , 5 )P2 instillation, indicating that PI( 4 , 5 )P2 stimulation was not secondary to endogenous β-adrenoceptor activation. PI( 4 , 5 )P2 amine instillation resulted in an intermediate alveolar fluid clearance stimulation, suggesting that, to reach maximal alveolar fluid clearance stimulation, PI( 4 , 5 )P2 must reside in cell membranes. In summary, PI( 4 , 5 )P2 instillation upregulated in vivo alveolar fluid clearance similar to short-term β-adrenoceptor upregulation of alveolar fluid clearance. PI( 4 , 5 )P2 stimulation was mediated partly by increased amiloride-sensitive Na transport. There exist important gender-related effects suggesting a female advantage that may have clinical implications for resolution of acute lung injury.


1981 ◽  
Vol 98 (3) ◽  
pp. 396-401 ◽  
Author(s):  
B. Stringer ◽  
D. Wynford-Thomas ◽  
B. Jasani ◽  
E. D. Williams

Abstract. Adult male rats were fed a goitrogen, aminotriazole, for 74 days at a dose known to suppress thyroid function completely. At the end of this period, these animals along with matched controls were killed in groups of seven at 3 hourly intervals throughout a 24 hour period, and serum TSH, T3, T4 and albumin assayed. No significant circadian rhythms of T3, T4 or albumin were found in either, but a highly significant rhythm of TSH was demonstrated both in controls and goitrogen treated groups, with a diminished relative amplitude in the latter. The results indicate that a significant diurnal rhythm of serum TSH persists in the rat despite long-term blockade of thyroid hormone synthesis and that the existence of this rhythm is therefore independent of the presence of circulating T3 or T4.


2011 ◽  
Vol 89 (9) ◽  
pp. 623-630 ◽  
Author(s):  
Wael M. El-Sayed ◽  
Mohamed Ali Al-Kahtani

Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140–170 g). Oseltamivir was administered at 2.2 mg·kg–1·day–1 for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats.


1979 ◽  
Vol 237 (3) ◽  
pp. E224 ◽  
Author(s):  
F Azizi

As the age of young adult male rats increased from 30 to 150 days, the serum thyroxine (T4) decreased by 50% and the serum thyroid-stimulating hormone (TSH) increased by 250%. There was no change in the serum triiodothyronine (T3). The increment in serum TSH after injection of thyrotropin-releasing hormone (TRH) was not significantly different at any of the ages studied, but the old animals had significantly lower increments in serum T4 and T3 after subcutaneous administration of bovine TSH. Despite a higher basal serum TSH, the older rats had a lesser increase in serum TSH after thyroidectomy or propylthiouracil. Thus, 1) there is a progressive decline in intrinsic thyroid function between 30 and 150 days of age in male rats, and 2) pituitary TSH response to fall in serum concentration of thyroid hormones is also decreased with age.


Sign in / Sign up

Export Citation Format

Share Document