Age-related alterations in prolactin binding sites in the female rat

1991 ◽  
Vol 124 (3) ◽  
pp. 314-321 ◽  
Author(s):  
Philippe Schneiter ◽  
Marianne J. Reymond ◽  
Thérèse Lemarchand-Béraud

Abstract. Aging is associated with various neuroendocrine alterations, including in the rat a hypersecretion of PRL with maintained ovulations (repetitive pseudopregnancy) and a reduced activity of the hypothalamic dopaminergic neurons with loss of the neuron responsiveness to PRL, suggestive of age-related alterations in PRL receptors. In this study we have investigated PRL binding sites in the hypothalamus as well as in the mammary glands, the ovaries and the liver of young and old nulliparous female rats. The old rats (26-28 months) displayed spontaneous repetitive pseudopregnancies and they were compared with young (4-6 months) pseudopregnant rats; the binding studies were performed by saturation analysis using 125I-oPRL as ligand and particulate membrane preparations. In the hypothalamus, a negligible binding of PRL was observed in all fragments studied, mediobasal hypothalamus, median eminence, in both young and old rats and no characterization of the binding sites could be achieved. In the mammary glands, the number of PRL binding sites was appreciable in spite of the nulliparity of the rats, but it was smaller in the old than in the young rats (9.0±1.4 vs 14.9±1.2 fmol/mg protein; mean ± sem; p<0.02). In the ovaries, the density of PRL binding sites was similar in the old and young rats (112.6±9.7 vs 115.0±8.9 fmol/mg protein), illustrative of a maintained luteotropic effect of PRL with age in the rat. In contrast, in the liver a greater number of binding sites was found in the old than in the young rats (261.9±36.6 vs 63.6±5.8 fmol/mg protein; p<0.001), supportive of the ability of PRL to induce its own receptors in that tissue. The affinity constant of PRL binding was not altered with age in the tissues studied. These results are illustrative of tissue-specific modifications in the number of PRL binding sites with age and they are suggestive of a sustained biological activity of PRL in the old rats.

1978 ◽  
Vol 78 (2) ◽  
pp. 225-232 ◽  
Author(s):  
H. J. CHEN ◽  
P. G. WALFISH

SUMMARY The effects of ovariectomy and ovariectomy and treatment with oestradiol benzoate (OB) on the basal concentration of thyrotrophin (TSH), the total concentrations and concentrations of free tri-iodothyronine (T3) and thyroxine (T4), and the concentrations of TSH, T3 and T4 observed after treatment with thyrotrophin releasing hormone (TRH) were studied in old (16–17 months of age) constant oestrous and young (3–4 months of age) oestrous rats. The untreated old control rats had significantly (P< 0·001) lower basal total T4 concentrations and percentage and absolute concentrations of free T4 and lower percentage and absolute concentrations of free T3 than untreated young rats. The basal levels of TSH in these two groups were similar and the increases in TSH after injection of TRH were identical. Two weeks after ovariectomy, no significant additional differences in hormone concentrations between old and young rats were observed. However, release of TSH induced by TRH was increased by three- to fourfold in old rats after ovariectomy compared with nine- to tenfold in young ovariectomized rats (P<0·01). Basal T4 concentrations remained unchanged in old ovariectomized rats treated for 7 days with 2 μg OB/day compared with both intact and ovariectomized rats. However, T4 concentrations in OB-treated young rats were significantly (P<0·001) reduced. Treatment with OB significantly increased both basal and TRH-induced T3 and TSH levels in old and young rats although the young rats showed a greater response (P<0·001). Two hours after injection of TRH, serum T3 concentrations in old rats increased only after OB treatment and not after ovariectomy alone or in intact rats, whereas T3 concentrations rose in all three groups of young animals. These results indicate that (1) older female rats have lower total T4, free T4 and free T3 concentrations and a lower TSH response to TRH, (2) OB treatment in young rats suppresses serum T4 but increases serum T3 and results in a greater TSH response to TRH and (3) at least one of the mechanisms accounting for the alterations in thyroid function observed in the older female rat, in addition to possible concomitant primary thyroid gland hypofunction, is a hyporesponsiveness of pituitary thyrotrophs to both endogenous negative feedback signals from low serum thyroid hormone concentrations and exogenous TRH stimulation.


1992 ◽  
Vol 262 (5) ◽  
pp. E557-E560
Author(s):  
C. L. Tsai ◽  
H. F. Pu ◽  
C. P. Lau ◽  
P. S. Wang ◽  
T. K. Liu

The effects of aging on calcitonin (CT) secretion in female rats were investigated. Old (24 mo) at constant diestrus status and young (2 mo) at diestrus status rats were either ovariectomized (Ovx) or left intact as controls. Ovx rats were injected subcutaneously with estradiol benzoate (25 micrograms/kg body wt) or sesame oil one time per day for 3 days. All rats were infused with CaCl2 (10 mg/ml) at a rate of 2 ml/h for 30 min via a jugular catheter connected to a peristaltic pump. Blood samples (0.5 ml each) were collected at 0, 30, 60, and 120 min. The basal and post-CaCl2 levels of plasma Ca measured with radioimmunoassay were significantly higher (P less than 0.05-0.01) in old than in young female rats. The pre- and post-CaCl2 levels of plasma Ca and CT in young rats were not altered by Ovx or estradiol replacement. In old rats, Ovx caused a higher (P less than 0.01) level in plasma CT at 0 and 30 min after CaCl2 infusion. Both basal and stimulated levels of plasma CT were higher (P less than 0.01) in old Ovx than in young Ovx rats. These results demonstrated that 1) the increase of plasma CT in response to Ca challenge was greater in old than in young female rats, 2) the influence of estradiol and ovarian function on plasma CT concentration increases as a function of age, and 3) estradiol reduced the plasma CT in response to hypercalcemia in old Ovx rats. The sensitivity of the target tissue of young rats may be lower in response to the modulation of estrogen during hypercalcemia without compromising the secretion and hypocalcemic effect of CT in young rats. All suggested an age-related relationship between estrogen and CT secretion in minute-to-minute regulation during Ca infusion in rats.


1990 ◽  
Vol 126 (3) ◽  
pp. 461-466 ◽  
Author(s):  
M. N. Sillence ◽  
R. G. Rodway

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


2012 ◽  
Vol 56 (4) ◽  
pp. 259-264 ◽  
Author(s):  
Claudia Cardoso Netto ◽  
Vivian Cristine Correia Vieira ◽  
Lizanka Paola Figueiredo Marinheiro ◽  
Sherry Agellon ◽  
Hope Weiler ◽  
...  

OBJECTIVE: To analyze if female Wistar rats at 56 weeks of age are a suitable model to study osteoporosis. MATERIALS AND METHODS: Female rats with 6 and 36 weeks of age (n = 8 per group) were kept over a 20-week period and fed a diet for mature rodents complete in terms of Ca, phosphorous, and vitamin D. Excised femurs were measured for bone mass using dual-energy x-ray absorptiometry, morphometry, and biomechanical properties. The following serum mar-kers of bone metabolism were analyzed: parathyroid hormone (PTH), osteocalcin (OC), osteoprotegerin (OPG), receptor activator of nuclear factor Κappa B ligand (RANKL), C-terminal peptides of type I collagen (CTX-I), total calcium, and alkaline phosphatase (ALP) activity. RESULTS: Rats at 56 weeks of age showed important bone metabolism differences when compared with the younger group, such as, highest diaphysis energy to failure, lowest levels of OC, CTX-I, and ALP, and elevated PTH, even with adequate dietary Ca. CONCLUSION: Rats at 26-week-old rats may be too young to study age-related bone loss, whereas the 56-week-old rats may be good models to represent the early stages of age-related changes in bone metabolism.


Author(s):  
Ming Cheng ◽  
Bo Tan ◽  
Xiaojing Wu ◽  
Feng Liao ◽  
Fei Wang ◽  
...  

Long-term and excessive alcohol consumption are risk factors for osteoporosis. Excessive drinking can reduce bone density and also cause imbalance of gut microbiota. And gut microbiota can affect bone metabolism through various mechanisms, and the regulation of gut microbiota is closely related to age. However, the effects of gut microbiota on alcohol-induced osteoporosis at different ages are unclear. In this study, young and old rats were used to induce osteoporosis by long-term alcohol consumption, and alcohol metabolism, bone morphology, bone absorption and immune activity of rats were analyzed to determine the effects of alcohol on rats of different ages. In addition, changes of gut microbiota in rats were analyzed to explore the role of gut microbiota in alcohol-induced osteoporosis in rats of different ages. The results showed the ability of alcohol metabolism was only associated with age, but not with alcohol consumption. Long-term alcohol consumption resulted in the changes of bone metabolism regulating hormones, bone loss, activation of receptor activator of NF-κB ligand (RANKL) signaling and inflammatory response. And osteoporosis was more severe in old rats than young rats, suggesting that alcohol-induced osteoporosis is age-related. In addition, long-term drinking also affected the composition of gut microbiota in rats, with a significant increase in the proportion of pro-inflammatory microorganisms. Overall, this study found that long-term alcohol consumption induced osteoporosis and affected the composition of gut microbiota. And alcohol can activate T lymphocytes directly or indirectly by regulating the changes of gut microbiota to produce cytokines, and further activate osteoclasts. In addition, the osteoporosis was more severe in the old rats than young rats, which may be due to the higher diversity and stronger regulation ability of gut microbiota in young rats compared with old rats.


1996 ◽  
Vol 271 (6) ◽  
pp. R1625-R1631 ◽  
Author(s):  
S. T. Davidge ◽  
C. A. Hubel ◽  
M. K. McLaughlin

We tested the hypothesis that an increase in endogenous lipid peroxidation over time is associated with an impairment of endothelium-dependent vascular function in resistance-sized mesenteric arteries that is due in part to alterations of arachidonate metabolism. Susceptibility to red blood cell hemolysis and sera levels of malondialdehyde were increased (P < 0.05) from 20 wk (n = 12) to 40 wk (n = 12) in female Sprague-Dawley rats. Arteries were studied in a myograph by examining the endothelial modification of phenylephrine vasoconstriction and the relaxation responses of the mesenteric arteries to methacholine. We observed the following. 1) An increase in sensitivity to alpha 1-adrenergic stimulation occurred between 20 and 40 wk of age. Cyclooxygenase inhibition decreased the sensitivity to phenylephrine only in the arteries from the 40-wk-old rats, indicating that a cyclooxygenase-dependent vasoconstrictor was modifying the phenylephrine response. 2) Nitric oxide synthase inhibition caused a greater increase in phenylephrine sensitivity in the arteries from the 20-wk-old rats than those from the 40-wk-old rats, indicating that nitric oxide modification of phenylephrine sensitivity decreased with age. 3) Endothelium-independent relaxations were not affected between 20 and 40 wk of age. 4) At 40 wk, the sensitivity to the methacholine-mediated relaxation response decreased without impairing the maximal relaxation response. This reduced sensitivity was removed with cyclooxygenase inhibition or thromboxane A2/prostaglandin H2 (PGH2) receptor blockade. 5) Aortas from the 40-wk-old rats had an increased expression of PGH synthase. Collectively, these observations indicate that, in the female rat, an increase in lipid peroxidation over time is associated with changes in endothelium-dependent vascular function that were due in part to a cyclooxygenase-dependent vasoconstrictor.


1982 ◽  
Vol 95 (1) ◽  
pp. 37-41 ◽  
Author(s):  
M. Wilkinson ◽  
R. Bhanot ◽  
J. A. Pincock ◽  
L. Donald

We have investigated whether sexual maturation in female rats is affected by repeated flurothyl-induced convulsions. This treatment had no effect on the normal age-related increase in body weight though puberty (vaginal opening) was significantly delayed when compared with non-convulsed control rats. In an attempt to probe the mechanism of this delaying effect we observed that (1) anterior pituitary response to gonadotrophin releasing hormone in vitro was normal in terms of LH release but FSH secretion was impaired and (2) progesterone injection in oestrogen-primed convulsed rats failed to generate an ovulatory-type surge of LH or FSH. Basal serum levels and basal in-vitro secretion of LH and FSH were normal. We conclude that repeated convulsions adversely affect the hypothalamo-pituitary-gonadotrophin system of immature female rats.


2008 ◽  
Vol 294 (4) ◽  
pp. R1165-R1174 ◽  
Author(s):  
Steven A. Bloomer ◽  
Kyle E. Brown ◽  
Garry R. Buettner ◽  
Kevin C. Kregel

Environmental heat stress is associated with an age-related increase in hepatic oxidative damage and an exaggerated state of oxidative stress. The purpose of this investigation was to evaluate the regulation of hepatic iron after heat stress. A secondary aim was to determine a potential role for iron in heat stress-induced liver injury. Hyperthermia-induced alterations in hepatic iron were evaluated in young (6 mo) and old (24 mo) Fischer 344 rats by exposing them to a two-heat stress protocol. Livers were harvested at several time points after the second heating and assayed for labile and nonheme iron. In the control condition, there was no difference in labile iron between age groups. Both labile iron and storage iron were not altered by hyperthermia in young rats, but both were increased immediately after heating in old rats. To evaluate a role for iron in liver injury, hepatic iron content was manipulated in young and old rats, and then both groups were exposed to heat stress. Iron administration to young rats significantly increased hepatic iron content and ferritin but did not affect markers of lipid peroxidation under control conditions or after heat stress. In old rats, iron chelation with deferoxamine prevented the increase in nonheme iron, labile iron, ferritin, and lipid peroxidation after heat stress. These results suggest that iron may play a role in hepatic injury after hyperthermia. Thus, dysregulation of iron may contribute to the gradual decline in cellular and physiological function that occurs with aging.


2011 ◽  
Vol 300 (4) ◽  
pp. R1001-R1008 ◽  
Author(s):  
Robert L. Thunhorst ◽  
Connie L. Grobe ◽  
Terry G. Beltz ◽  
Alan Kim Johnson

These experiments examined water-drinking and arterial blood pressure responses to β-adrenergic receptor activation in young (4 mo), “middle-aged” adult (12 mo), and old (29 mo) male rats of the Brown-Norway strain. We used isoproterenol to simultaneously activate β1- and β2-adrenergic receptors, salbutamol to selectively activate β2-adrenergic receptors, and the combination of isoproterenol and the β2-adrenergic receptor antagonist ICI 118,551 to stimulate only β1-adrenergic receptors. Animals received one of the drug treatments, and water drinking was measured for 90 min. About 1 wk later, animals received the same drug treatment for measurement of arterial blood pressure responses for 90 min. In some rats, levels of renin and aldosterone secretion in response to isoproterenol or salbutamol were measured in additional tests. Old and middle-aged rats drank significantly less after isoproterenol than did young rats and also had greater reductions in arterial blood pressure. Old and middle-aged rats drank significantly less after salbutamol than did young rats, although reductions in arterial blood pressure were equivalent across the ages. The β2-adrenergic antagonist ICI 118,551 abolished drinking after isoproterenol and prevented most of the observed hypotension. Renin secretion after isoproterenol and salbutamol was greater in young rats than in middle-aged rats, and wholly absent in old rats. Aldosterone secretion was reduced in old rats compared with young and middle-aged rats after treatment with isoproterenol, but not after treatment with salbutamol. In conclusion, there are age-related differences in β-adrenergic receptor-mediated drinking that can be explained only in part by age-related differences in renin secretion after β-adrenergic receptor stimulation.


1978 ◽  
Vol 79 (2) ◽  
pp. 191-199 ◽  
Author(s):  
N. S. WHITWORTH ◽  
C. E. GROSVENOR

Prolactin passes from the systemic circulation of lactating rats into the milk where it can be consumed by the young rats during suckling. 131I-Labelled rat prolactin was detected in the plasma of 9- to 14-day-old rats after being nursed by mothers previously injected with 131I-labelled rat prolactin and after the pups had received 131I-labelled rat prolactin by gastric intubation. It was estimated that 16% of the 131I-labelled rat prolactin given by gastric intubation subsequently appeared in the plasma of the neonate. Gastric administration of 10·5 or 21·0 μg B-1 rat prolactin significantly raised the level of prolactin in the plasma of 13-day-old pups, but a similar increase was not observed when 27-day-old rats were given 46·2 μg B-1 prolactin by gastric intubation. The concentration of prolactin in the plasma of 13- to 14-day-old rats rose to 55 ng/ml 30 min after the onset of nursing by mothers whose mammary glands were full of milk, whereas the concentration in the plasma of offspring suckled by mothers with empty mammary glands remained at basal values. It is concluded that the intestine of the newborn rat is permeable to prolactin and that milk may constitute an exogenous source of prolactin for the suckled offspring.


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