TSH SYNTHESIS AND RELEASE IN THE THYROIDECTOMIZED RAT:

1979 ◽  
Vol 92 (3) ◽  
pp. 489-501 ◽  
Author(s):  
O. Spira ◽  
A. Birkenfeld ◽  
J. Gross ◽  
A. Gordon
Keyword(s):  
Steady State ◽  
Compartmental Analysis ◽  
Fold Increase ◽  
Progressive Increase ◽  
Male Rats ◽  
Metabolic Clearance ◽  
Normal Value ◽  
Plateau Level ◽  
Tsh Levels ◽  
Stimulation Of

ABSTRACT Groups of surgically thyroidectomized (T) male rats were sacrificed at intervals during the period of 1 to 5 and 30 to 180 days after <UNK> Plasma T3, T4 and TSH levels and pituitary TSH content were measured by RIA. A drop of plasma T3 and T4 from normal to undetectable values occurred by day 3 post <UNK>. There was a progressive increase of plasma TSH from the normal value of 136 ± 14 ng/ml to 1623 ± 186 ng/ml (mean ± sem) at day 5 post T, reaching at 30 days a new plateau of 8618 ± 527 ng/ml. These levels remained unchanged up to 130 days post <UNK>. At 180 days, plasma TSH (4123 ± 991 ng/ml) fell significantly below the plateau level. Pituitary TSH content fell from the normal value of 80.9 ± 15.9 μg/mg to a nadir of 12.7 ± 1.4 μg/mg at day 4 post <UNK> and then slowly rose to 98.6 ± 5.9 μg/mg at 100 days, remaining at this level for another 30 days and finally declining significantly at 180 days post <UNK>. The rates of TSH release and synthesis were calculated using the metabolic clearance rates (MCR), determined from the curves of disappearance of injected [125I]-TSH by a non-compartmental analysis. The MCR values decreased, starting at 8 days after T, and reached about half the normal value from 30 days onwards (0.257 ± 0.03 to 0.144 ± 0.001 ml/min/100 g b.w.). The rate of TSH release was increased as early as the first day post <UNK>. A 6-fold increase was reached after 5 days and a new steady state of about 32-fold increase was attained within 1 month. TSH synthesis was also stimulated. However, it lagged behind the stimulation of the release for the first 4 days after <UNK>. The data indicate that: a) The depletion of thyroid hormones affects both synthesis and release of TSH. b) Under prolonged hypothyroidism TSH release and synthesis are in equilibrium, at a markedly enhanced rate. c) Very severe and prolonged hypothyroidism results in a decline in both pituitary and plasma TSH levels.

Effects of graded doses of triiodothyronine on TSH synthesis and secretion rates in hypothyroid rats

1981 ◽  
Vol 97 (1) ◽  
pp. 74-84 ◽  
Author(s):  
Th. Lemarchand-Béraud ◽  
C. Berthier
Keyword(s):  
Fold Increase ◽  
High Plasma ◽  
Male Rats ◽  
Slight Reduction ◽  
Metabolic Clearance ◽  
Clearance Rates ◽  
Tsh Secretion ◽  
Previously Treated ◽  
Secretion Rates ◽  
Tsh Levels

Abstract. The effects of a graded low dose of T3 on plasma TSH, anterior pituitary TSH content (AP-TSH) and on TSH synthesis and secretion rates, were studied in adult male rats previously treated for 7 days with 0.01% prophylthiouracil (PTU). Pituitary TSH content, plasma T3, T4 and TSH levels were measured by RIA at 0, 6, 12, 24 h after the injection of T3 ranging from 0.1 to 0.75 μg/100 g b.w. Saline treated normal rats served as control. The 7-day PTU treated rats displayed low but still detectable thyroid hormone plasma levels; high plasma TSH levels were observed, but with no further increase after TRH injection as the AP-TSH content was depleted. Injections of T3 increased plasma T3 in proportion with the dose given. Plasma T4 remained low and there was no significant decrease in plasma TSH until doses of 0.2 μg/100 g b.w. T3 was given. Then the transient TSH depression was dose-dependent from 0.2 to 0.75 μg/100 g b.w. The AP-TSH content increased regularly from 0.2 μg/T3 onwards, overlapping the transient inhibition of TSH secretion resulting in a 3-fold increase in the AP-TSH content, suggesting a positive action of T3 on TSH synthesis. In addition, TSH response to TRH was observed at every time studied after T3 injection. Then, the different groups were injected with [125I]rTSH in order to estimate metabolic clearance rates, TSH secretion and synthesis rates. The half-life of [125I]rTSH (22 min) and its metabolism clearance rates (16 ± 0.4 ml/h/100 g b.w.) were found similar in all groups. Whereas the TSH secretion rates was highly reduced in the normal rats receiving 0.3 μg T3 (156 ± 9 vs 408 ± 22 μg/24 h in normal rats), the PTU group displayed a 3-fold increased secretion rate (1222 ± 44 μg/24 h) which was not modified by the injection of 0.1–0.2 μg T3 and decreased to 868 and 472 μg/24 h with 0.3 μg and 0.75 μg T3, respectively. TSH synthesis rates were found highly increased in the PTU group (1222 ± 44 μg/d vs 408 ± 22 μg/d in normal rats) and was neither increased nor reduced in the 7-day PTU rats receiving 0.1–0.3 μg T3 but a slight reduction was observed only in the 0.75 μg T3 group. These data show that 0.1–0.2 μg/100 g b.w. T3 changed neither TSH secretion nor its synthesis rates while 0.3 μg more or less a replacement dose inhibited TSH secretion without changing TSH synthesis rates, resulting in a AP-TSH replenishment. Therefore, no direct positive effect of low doses of T3 on TSH synthesis could be demonstrated over 24 h while higher doses are capable of inhibiting first secretion and then synthesis of TSH.

Trans-stimulation of 13NH4+ efflux provides evidence for the cytosolic origin of tracer in the compartmental analysis of barley roots

2003 ◽  
Vol 30 (12) ◽  
pp. 1233 ◽  
Author(s):  
Dev T. Britto ◽  
Herbert J. Kronzucker
Keyword(s):  
Compartmental Analysis ◽  
Fold Increase ◽  
Model System ◽  
Hordeum Vulgare L ◽  
Root Cells ◽  
Transport Studies ◽  
Efflux Kinetics ◽  
Insight Into ◽  
Pool Sizes ◽  
Stimulation Of

The analysis of tracer efflux kinetics is fundamental to membrane transport studies, but requires the rigorous identification of subcellular tracer sources. We present a solution to this problem through the analysis of sharp increases in 13NH4+ efflux from roots of radiolabelled barley (Hordeum vulgare L.) seedlings, in response to a 100-fold increase in external [NH4+]. By comparing these trans-stimulation data with a mathematical model incorporating changes in subcellular NH4+ fluxes and pool sizes, we show that the cytosol of root cells is the origin of the tracer efflux. Our analysis provides new insight into the rapidly occurring events underlying compensatory flux regulation during transitions from one nutritional steady state to another, and confirms the validity of compartmental analysis by tracer efflux (CATE) in this important model system.

scholarly journals Evidence that lanthanum ions stimulate calcium inflow to isolated hepatocytes

1981 ◽  
Vol 200 (1) ◽  
pp. 109-114 ◽  
Author(s):  
J C Parker ◽  
G J Barritt
Keyword(s):  
Plasma Membrane ◽  
Steady State ◽  
Initial Rate ◽  
Compartmental Analysis ◽  
Isolated Hepatocytes ◽  
Lanthanum Ions ◽  
Isolated Liver Cells ◽  
Isolated Liver ◽  
Predominant Effect ◽  
Stimulation Of

LaCl3 stimulated the initial rate of 45Ca2+ exchange measured under steady-state conditions in isolated liver cells. Cu2+ greater than La3+ = Fe3+ greater than Fe2+ = Zn2+ greater Ni2+ greater than Mn2+ also stimulated 45Ca2+ exchange. Compartmental analysis of 45Ca2+-exchange curves obtained in the presence or absence of La3+, and in the presence or absence of adrenaline, showed that the predominant effect of La3+ is to stimulate the inflow of Ca2+ to the cell from the medium. No evidence for an inhibition of Ca2+ outflow from the cell was obtained. In the presence of La3+, adrenaline caused no further stimulation of Ca2+ inflow to the cell. In the absence of adrenaline, La3+ increased the uptake of Ca2+ (measured by atomic-absorption spectroscopy) by isolated hepatocytes incubated at 1 degree C. The proposal that La3+ stimulates Ca2+ inflow to the liver cell by inducing a conformational change in the Ca2+-inflow transporter of the plasma membrane is briefly discussed.

SECRETION RATE AND METABOLIC CLEARANCE RATE OF PROLACTIN IN THE RAT DURING MID- AND LATE LACTATION

1979 ◽  
Vol 82 (3) ◽  
pp. 409-415 ◽  
Author(s):  
C. E. GROSVENOR ◽  
N. S. WHITWORTH
Keyword(s):  
Plasma Concentration ◽  
Clearance Rate ◽  
Secretion Rate ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Urethane Anaesthesia ◽  
Plateau Level ◽  
Stimulation Of

The prolactin concentration in the plasma of lactating rats rose less rapidly and attained a significantly lower plateau level in response to suckling on day 20–21 of lactation than it did on day 13–14 of lactation. Neither differences in suckling stimulation of the older pups nor a higher metabolic clearance rate (MCR) of prolactin were implicated in the reduced prolactin concentration seen in the late-lactating rats. The MCR was, in fact, slightly reduced in both conscious and late-lactating rats anaesthetized with urethane when compared with those in mid-lactation. The MCR of prolactin was not significantly altered by urethane anaesthesia in rats on either day of lactation. However, the secretion rate of prolactin, computed from the MCR multiplied by the equilibrum concentration of prolactin during suckling, was considerably reduced (665 to 392 ng/min) from mid- to late lactation. We conclude from these data that the reduced plasma concentration of prolactin in response to suckling in late lactation is the result of an impairment within the prolactin secretory mechanism.

Validation of a single-compartment approach to the calculation of secretion rates of ACTH

1978 ◽  
Vol 56 (3) ◽  
pp. 410-415 ◽  
Author(s):  
John S. Cowan
Keyword(s):  
Steady State ◽  
Infusion Rate ◽  
Fold Increase ◽  
Rapid Decline ◽  
Metabolic Clearance ◽  
Time Data ◽  
Plasma Acth ◽  
Entry Rate ◽  
Single Compartment ◽  
Secretion Rates

A single-compartment model used in this laboratory for continuously calculating ACTH secretion rates from measured plasma ACTH concentrations has been tested for its ability to follow changing rates of ACTH entry (rapid departure from steady state). ACTH was infused at known moderately high but physiological rates into anaesthetized dogs (Nembutal). Under such conditions endogenous secretion is initially <5% of infused rates. Orthogonal polynomials (ACTHt) were fitted to plasma ACTH vs. time data. Then [Formula: see text] where it was previously shown that the metabolic clearance rate of ACTH (MCR) lacked significant inter-animal or concentration-dependent variation, and its distribution volume (V) was also constant.The calculated ACTH entry rate curves (a) followed a 10-fold increase in infusion rate over 4 min and subsequent rapid decline with a lag of only about 1 min and, despite some blurring, gave an integrated response equal to 94 ± 5.5% of the known signal, and (b) followed a sinusoidal change in infusion rate (amplitude, 1.7 × base rate; period, 40 min) with a few percent error and negligible lag. These signals imitate (a) an abrupt stress response, and (b) other rapid departures from steady state.

DER EINFLUSS VON RESERPIN AUF DIE ANTITHYREOIDALE WIRKUNG VON KALIUMPERCHLORAT

1962 ◽  
Vol 39 (3) ◽  
pp. 423-430
Author(s):  
H. L. Krüskemper ◽  
F. J. Kessler ◽  
E. Steinkrüger
Keyword(s):  
Thyroid Gland ◽  
Male Rats ◽  
Normal Male ◽  
Tissue Respiration ◽  
List Type ◽  
Morphological Alterations ◽  
Hormone Synthesis ◽  
Stimulation Of

ABSTRACT 1. Reserpine does not inhibit the tissue respiration of liver in normal male rats (in vitro). 2. The decrease of tissue respiration of the liver with simultaneous morphological stimulation of the thyroid gland after long administration of reserpine is due to a minute inhibition of the hormone synthesis in the thyroid gland. 3. The morphological alterations of the thyroid in experimental hypothyroidism due to perchlorate can not be prevented with reserpine.

INDUCTION OF GOITRE BY PTU OR KClO4 IN MALE AND FEMALE RATS. EFFECT OF GONADECTOMY

1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia
Keyword(s):  
Iodine Content ◽  
High Plasma ◽  
Disc Electrophoresis ◽  
Female Rats ◽  
Male Rats ◽  
Adult Rats ◽  
Male And Female ◽  
Glucose Levels ◽  
Male And Female Rats ◽  
Tsh Levels

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.

scholarly journals Receptor-operated Ca2+ channels in gastric parietal cells: gastrin and carbachol induce Ca2+ influx in depleting intracellular Ca2+ stores

1993 ◽  
Vol 289 (1) ◽  
pp. 117-124 ◽  
Author(s):  
S Roche ◽  
J P Bali ◽  
R Magous
Keyword(s):  
Steady State ◽  
Receptor Activation ◽  
Parietal Cells ◽  
The Other ◽  
Bivalent Cation ◽  
Gtp Binding ◽  
Gastric Parietal Cells ◽  
Type Receptor ◽  
Ca2 Channels ◽  
Stimulation Of

The mechanism whereby gastrin-type receptor and muscarinic M3-type receptor regulate free intracellular Ca2+ concentration ([Ca2+]i) was studied in rabbit gastric parietal cells stimulated by either gastrin or carbachol. Both agonists induced a biphasic [Ca2+]i response: a transient [Ca2+]i rise, followed by a sustained steady state depending on extracellular Ca2+. Gastrin and carbachol also caused a rapid and transient increase in Mn2+ influx (a tracer for bivalent-cation entry). Pre-stimulation of cells with one agonist drastically decreased both [Ca2+]i increase and Mn2+ influx induced by the other. Neither diltiazem nor pertussistoxin treatment had any effect on agonist-stimulated Mn2+ entry. Thapsigargin, a Ca(2+)-pump inhibitor, induced a biphasic [Ca2+]i increase, and enhanced the rate of Mn2+ entry. Preincubation of cells with thapsigargin inhibits the [Ca2+]i increase as well as Mn2+ entry stimulated by gastrin or by carbachol. Thapsigargin induced a weak but significant increase in Ins(1,4,5)P3 content, but this agent had no effect on the agonist-evoked Ins(1,4,5)P3 response. In permeabilized parietal cells, Ins(1,4,5)P3 and caffeine caused an immediate Ca2+ release from intracellular pools, followed by a reloading of Ca2+ pools which can be prevented in the presence of thapsigargin. We conclude that (i) gastrin and carbachol mobilize common Ca2+ intracellular stores, (ii) Ca2+ permeability secondary to receptor activation involves neither a voltage-sensitive Ca2+ channel nor a GTP-binding protein from the G1 family, and (iii) agonists regulate common Ca2+ channels in depleting intracellular Ca2+ stores.

scholarly journals FGF23, a novel muscle biomarker detected in the early stages of ALS

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ying Si ◽  
Mohamed Kazamel ◽  
Michael Benatar ◽  
Joanne Wuu ◽  
Yuri Kwon ◽  
...  
Keyword(s):  
Biomarker Discovery ◽  
Clinical Symptoms ◽  
Early Stage ◽  
Fold Increase ◽  
Progressive Increase ◽  
Molecular Signature ◽  
Muscle Membrane ◽  
Sequencing Project ◽  
Progressive Muscle Weakness ◽  
End Stage

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness. Skeletal muscle is a prime source for biomarker discovery since it is one of the earliest sites to manifest disease pathology. From a prior RNA sequencing project, we identified FGF23 as a potential muscle biomarker in ALS. Here, we validate this finding with a large collection of ALS muscle samples and found a 13-fold increase over normal controls. FGF23 was also increased in the SOD1G93A mouse, beginning at a very early stage and well before the onset of clinical symptoms. FGF23 levels progressively increased through end-stage in the mouse. Immunohistochemistry of ALS muscle showed prominent FGF23 immunoreactivity in the endomysial connective tissue and along the muscle membrane and was significantly higher around grouped atrophic fibers compared to non-atrophic fibers. ELISA of plasma samples from the SOD1G93A mouse showed an increase in FGF23 at end-stage whereas no increase was detected in a large cohort of ALS patients. In conclusion, FGF23 is a novel muscle biomarker in ALS and joins a molecular signature that emerges in very early preclinical stages. The early appearance of FGF23 and its progressive increase with disease progression offers a new direction for exploring the molecular basis and response to the underlying pathology of ALS.

scholarly journals Dengue Virus Induces the Expression and Release of Endocan from Endothelial Cells by an NS1–TLR4-Dependent Mechanism

2021 ◽  
Vol 9 (6) ◽  
pp. 1305
Author(s):  
Carlos Alonso Domínguez-Alemán ◽  
Luis Alberto Sánchez-Vargas ◽  
Karina Guadalupe Hernández-Flores ◽  
Andrea Isabel Torres-Zugaide ◽  
Arturo Reyes-Sandoval ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Mrna Expression ◽  
Cell Lines ◽  
Cell Activation ◽  
Dengue Infection ◽  
Elevated Serum ◽  
Fold Increase ◽  
Endothelial Cell Activation ◽  
Stimulation Of

A common hallmark of dengue infections is the dysfunction of the vascular endothelium induced by different biological mechanisms. In this paper, we studied the role of recombinant NS1 proteins representing the four dengue serotypes, and their role in promoting the expression and release of endocan, which is a highly specific biomarker of endothelial cell activation. We evaluated mRNA expression and the levels of endocan protein in vitro following the stimulation of HUVEC and HMEC-1 cell lines with recombinant NS1 proteins. NS1 proteins increase endocan mRNA expression 48 h post-activation in both endothelial cell lines. Endocan mRNA expression levels were higher in HUVEC and HMEC-1 cells stimulated with NS1 proteins than in non-stimulated cells (p < 0.05). A two-fold to three-fold increase in endocan protein release was observed after the stimulation of HUVECs or HMEC-1 cells with NS1 proteins compared with that in non-stimulated cells (p < 0.05). The blockade of Toll-like receptor 4 (TLR-4) signaling on HMEC-1 cells with an antagonistic antibody prevented NS1-dependent endocan production. Dengue-infected patients showed elevated serum endocan levels (≥30 ng/mL) during early dengue infection. High endocan serum levels were associated with laboratory abnormalities, such as lymphopenia and thrombocytopenia, and are associated with the presence of NS1 in the serum.

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