AGE-RELATED CHANGES IN THE DEGRADATION OF THYROTROPHIN RELEASING HORMONE BY HUMAN AND RAT SERUM

1980 ◽  
Vol 86 (3) ◽  
pp. 397-402 ◽  
Author(s):  
NICKI WHITE ◽  
E. C. GRIFFITHS ◽  
S. L. JEFFCOATE ◽  
R. D. G. MILNER ◽  
M. A. PREECE

Changes in the rate of in-vitro degradation of thyrotrophin releasing hormone (TRH) in serum as related to age have been investigated in the rat and man. In rats, no inactivation was found up to the age of 15 days but thereafter an age-related increase in inactivation was detected with approximately 75% inactivation in 60 min at 40 days and reaching a maximum of 88–93% inactivation in adult male and female animals. The human serum samples studied (both male and female) showed a similar but less clear-cut pattern of inactivation of TRH compared with that found in the rat. A physiological role for these age-related changes in the degradation of TRH remains to be established but it has been concluded that the changes observed in both rat and man may be associated with growth and development, possibly by facilitating feedback control of thyrotrophin secretion through the degradation of TRH.

1976 ◽  
Vol 71 (1) ◽  
pp. 13-19 ◽  
Author(s):  
N. WHITE ◽  
S. L. JEFFCOATE ◽  
E. C. GRIFFITHS ◽  
K. C. HOOPER

SUMMARY The TRH-degrading activity of rat serum in vitro is five times more potent than that of human serum. In rats, it is significantly reduced in hypothyroidism (thiouracil-induced) and significantly increased in hyperthyroidism (T3 or T4-induced). This suggests a possible role in the regulation of adenohypophysial-thyroid function which is probably, in turn, dependent on thyroid hormone, rather than TSH, levels.


1983 ◽  
Vol 104 (3) ◽  
pp. 319-326 ◽  
Author(s):  
J. M. Kaufman ◽  
A. Elewaut ◽  
A. Vermeulen

Abstract. Levels of immunoreactive thyrotrophin-releasing hormone like material (IR-TRH LM) were measured in paired maternal and umbilical cord serum samples (n = 45) and in serum of non-pregnant women (n = 63), using a sensitive and specific radioimmunoassay. In all pairs IR-TRH LM in venous cord serum (mean 91.3 pg/ml, range 20–270) was markedly elevated as compared to maternal serum (mean 13.5 pg/ml, range 0–37, P < 0.001, the maternal levels being similar to those in non-pregnant women (mean 12.0 pg/ml, range 0–39, P > 0.1). In 23 cases IR-TRH LM was also measured in arterial cord serum: arterial and venous cord levels were highly significantly correlated (r = 0.904) with higher arterial levels in 22 out of 23 cases (mean 117.8 pg/ml, range 32–280 and 90.6 pg/ml, range 20–270, P < 0.001), suggesting that cord IR-TRH LM is not of placental origin. There was no correlation between individual levels of IR-TRH LM and either TSH, T4, T3 or FT4 levels in either maternal or cord serum. Agar gel electrophoresis and equilibrium dialysis of adult and cord serum pre-incubated with [125I]TRH or [3H]TRH revealed no protein binding. Cord IR-TRH LM was immunologically, as well as in paper electrophoresis and in gelfiltration, indistinguishable from synthetic and hypothalamic TRH. In vitro degradation of synthetic TRH was much slower in cord serum as compared to maternal and control serum (P < 0.001). In vitro degradation of cord IRTRH LM could not be demonstrated, neither by cord serum itself nor by adult serum, this in contrast to hypothalamus extracted TRH which was readily degraded by adult serum. Neither the presence of an inhibiting substance, nor methodological factors seem to account for the apparently different behaviour of cord IR-TRH. It is suggested that circulating IR-TRH could be closely related, but still different from tissue extracted and synthetic TRH.


1996 ◽  
Vol 85 (4) ◽  
pp. 373-376 ◽  
Author(s):  
Patricia W. Slattum ◽  
Allen E. Cato ◽  
Gary M. Pollack ◽  
Kim L.R. Brouwer

1982 ◽  
Vol 54 (4) ◽  
pp. 763-768 ◽  
Author(s):  
Ronald E. Allen ◽  
Gail Robinson ◽  
Matthew J. Parsons ◽  
Robert A. Merkel ◽  
William T. Magee

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1473
Author(s):  
Belal I. Hanafy ◽  
Gareth W. V. Cave ◽  
Yvonne Barnett ◽  
Barbara K. Pierscionek

Cerium oxide nanoparticles (nanoceria) are generally known for their recyclable antioxidative properties making them an appealing biomaterial for protecting against physiological and pathological age-related changes that are caused by reactive oxygen species (ROS). Cataract is one such pathology that has been associated with oxidation and glycation of the lens proteins (crystallins) leading to aggregation and opacification. A novel coated nanoceria formulation has been previously shown to enter the human lens epithelial cells (HLECs) and protect them from oxidative stress induced by hydrogen peroxide (H2O2). In this work, the mechanism of nanoceria uptake in HLECs is studied and multiple anti-cataractogenic properties are assessed in vitro. Our results show that the nanoceria provide multiple beneficial actions to delay cataract progression by (1) acting as a catalase mimetic in cells with inhibited catalase, (2) improving reduced to oxidised glutathione ratio (GSH/GSSG) in HLECs, and (3) inhibiting the non-enzymatic glucose-induced glycation of the chaperone lens protein α-crystallin. Given the multifactorial nature of cataract progression, the varied actions of nanoceria render them promising candidates for potential non-surgical therapeutic treatment.


1977 ◽  
Vol 72 (3) ◽  
pp. 301-311 ◽  
Author(s):  
A. E. PANERAI ◽  
IRIT GIL-AD ◽  
DANIELA COCCHI ◽  
V. LOCATELLI ◽  
G. L. ROSSI ◽  
...  

SUMMARY To determine how the sensitivity of the ectopic anterior pituitary gland to the GH-releasing effect of thyrotrophin releasing hormone (TRH) might be affected by the time lapse from transplantation, TRH (0·15 and 0·6 μg) was injected i.v. into hypophysectomized (hypox)-transplanted rats under urethane anaesthesia 1,3, 8,15, 30 and 60 days after transplantation, and plasma samples were taken 5 and 10 min later. Baseline GH values gradually decreased with time from about 16·0 ng/ml (1 day) to about 3·0 ng/ml (30 and 60 days). The TRH-induced GH release was absent 1 day after transplantation, present only with the higher TRH dose 3 and 8 days after transplantation, and clearly elicitable, also with the lower TRH dose (0·15 μg), from 15 up to 60 days. Determination of plasma prolactin concentrations showed a decline from about 85·0 ng/ml (1 day) to about 32·0 ng/ml (8 days); subsequently (15–60 days) prolactin values stabilized. Plasma prolactin levels increased 15 and 60 days after transplantation only when a dose of 0·6 μg TRH was given. In intact weight-matched rats, TRH induced a GH response only at the dose of 1·2 μg while a short-lived but clear-cut prolactin response could be obtained even with the 0·3 μg dose. The present results indicate that: (1) disconnexion between the central nervous system and the anterior pituitary gland greatly enhances GH responsiveness while blunting prolactin responsiveness to TRH; (2) the sensitivity of the anterior pituitary gland to the GH-releasing effect of TRH increases with time from transplantation; (3) TRH is a more effective prolactin-than GH-releaser on the pituitary gland in situ.


2005 ◽  
Vol 38 (2) ◽  
pp. 245-256 ◽  
Author(s):  
L WILLEMS ◽  
A ZATTA ◽  
K HOLMGREN ◽  
K ASHTON ◽  
J HEADRICK

2003 ◽  
Vol 73 (2) ◽  
pp. 120-126 ◽  
Author(s):  
Cassidy

Interest in the physiological role of bioactive compounds present in plants has increased dramatically over the last decade. Of particular interest in relation to human health are the class of compounds known as the phytoestrogens, which embody several groups of non-steroidal oestrogens including isoflavones & lignans that are widely distributed within the plant kingdom. Data from animal and in vitro studies provide plausible mechanisms to explain how phytoestrogens may influence hormone dependent states, but although the clinical application of diets rich in these oestrogen mimics is in its infancy, data from preliminary studies suggest potential beneficial effects of importance to health. Phytoestrogens are strikingly similar in chemical structure to the mammalian oestrogen, oestradiol, and bind to oestrogen receptors (ER) with a preference for the more recently described ERb. This suggests that these compounds may exert tissue specific effects. Numerous other biological effects independent of the ER (e.g. antioxidant capacity, antiproliferative and antiangiogenic effects) have been ascribed to these compounds. Whether phytoestrogens have any biological activity in humans, either hormonal or non hormonal is a contentious issue and there is currently a paucity of data on human exposure. Much of the available data on the absorption and metabolism of dietary phytoestrogens is of a qualitative nature; it is known that dietary phytoestrogens are metabolised by intestinal bacteria, absorbed, conjugated in the liver, circulated in plasma and excreted in urine. Recent studies have addressed quantitatively what happens to isoflavones following ingestion – with pure compound and stable isotope data to compliment recent pharmacokinetic data for soy foods. The limited studies conducted so far in humans clearly confirm that soya isoflavones can exert hormonal effects. These effects may be of benefit in the prevention of many of the common diseases observed in Western populations (such as breast cancer, prostate cancer, menopausal symptoms, osteoporosis) where the diet is typically devoid of these biologically active naturally occurring compounds. However since biological effects are dependent on many factors including dose, duration of use, protein binding affinity, individual metabolism and intrinsic oestrogenic state, further clinical studies are necessary to determine the potential health effects of these compounds in specific population groups. However we currently know little about age related differences in exposure to these compounds and there are few guidelines on optimal dose for specific health outcomes.


Genetika ◽  
2014 ◽  
Vol 46 (1) ◽  
pp. 287-301 ◽  
Author(s):  
Biljana Bufan ◽  
Jasmina Djikic ◽  
Mirjana Nacka-Aleksic ◽  
Zorica Stojic-Vukanic ◽  
Mirjana Dimitrijevic ◽  
...  

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis, a prototype of Th1/Th17-mediated organ-specific autoimmune disease. In the rat, susceptibility to development of these diseases is shown to be strain-and age-dependent. In adult rats of distinct strains, it correlates with splenic dendritic cell (DC) subset composition, which also exhibit age-related changes. The aim of this study was to examine influence of aging on: i) Albino Oxford (relatively resistant to EAE) and Dark Agouti (susceptible to EAE) rat development of EAE and ii) their splenic conventional (OX62+) DC population in respect to its subset composition and expression of mRNAs for proinflammatory and immunosuppressive cytokines. We used 3month-old (young) and 26-month-old (aged) rats of AO and DA strain. The rats were immunized for EAE with rat spinal cord homogenate in complete Freund?s adjuvant and clinical course of the disease was followed. Fresh OX62+DCs were examined for the expression of CD4 (using flow cytometry) and genes encoding cytokines influencing DC activation/maturation (TNF-? and IL-6) using RT-PCR. Additionally, in vitro lipopolysaccharide (LPS) activated/matured DCs were examined for the expression of genes encoding cytokines controlling Th1/Th17 cell polarization using RT-PCR. With aging, AO rats became more susceptible, whereas DA rats largely lose their susceptibility to the induction of EAE. In AO rats aging shifted CD4+:CD4DC ratio towards CD4-cells, producing large amount of proinflammatory cytokines, whereas in DA rats CD4+:CD4-DC ratio remained stable with aging. In fresh DCs from rats of both the strains the expression of TNF-? mRNA increased with aging, whereas that of IL-6 mRNA decreased and increased in DCs from AO and DA rats, respectively. Following in vitro LPS stimulation OX62+ DCs from aged AO rats up-regulated the expression of mRNA for IL-23p19 (specific subunit of IL-23; crucial for sustained IL-17 production) and IL-1? (positive IL-17 regulator), whereas down-regulated the expression of IL-10 (negative IL-17 regulator) when compared with young strain-matched rats. In DA rats aging incresed IL-23p19 mRNA expression in LPS-stimulated DCs, whereas exerted the opposing effects on the expression of mRNAs for IL-10 and IL-1? compared to AO rats. Irrespective of the rat strain, aging did not influence mRNA expression for IL-12p35 (driving Th1 polarization) in DCs. Overall, results suggest role of changes in the expression of genes encoding proinflammatory and immunosuppressive cytokines in development of age-related alterations in rat susceptibility to EAE induction.


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