scholarly journals Central and peripheral administration of kisspeptin activates gonadotropin but not somatotropin secretion in prepubertal gilts

Reproduction ◽  
2008 ◽  
Vol 135 (6) ◽  
pp. 879-887 ◽  
Author(s):  
Clay A Lents ◽  
Neely L Heidorn ◽  
C Richard Barb ◽  
J Joe Ford
Keyword(s):  
Hormone Secretion ◽  
Domestic Animals ◽  
Laboratory Animals ◽  
Dependent Manner ◽  
Serum Concentrations ◽  
Blood Samples ◽  
Somatotropic Hormone ◽  
Gh Secretion ◽  
To Receive ◽  
Dose Dependent

It is well established that kisspeptin signaling is necessary for the onset of puberty in laboratory animals. However, the role that kisspeptin may have in regulating puberty in large domestic animals is unknown. We tested the hypothesis that either central or peripheral infusion of kisspeptin would stimulate gonadotropin and GH secretion in prepubertal gilts. In experiment 1, prepubertal gilts were fitted with i.c.v. cannula and indwelling jugular catheters. Animals were randomly assigned to receive 0, 10, or 100 μg kisspeptin in saline. In experiment 2, prepubertal gilts, fitted with indwelling jugular catheters, randomly received 0, 1, 2.5, or 5 mg kisspeptin in saline intravenously. Serial blood samples were collected every 15 min for 3 h before and 5 h after infusions, and serum concentrations of LH, FSH, and GH were determined. Mean concentrations of LH and FSH remained at basal levels for control animals but were increased (P<0.001) for animals receiving i.c.v. infusion of kisspeptin. Area under the LH and FSH curves following i.c.v. infusion of kisspeptin increased (P<0.001) in a dose-dependent manner. Concentrations of GH were unaffected by i.c.v. treatment. Peripheral administration of kisspeptin increased (P<0.05) serum concentrations of LH but not FSH or GH. Thus, kisspeptin can activate gonadotropic but not somatotropic hormone secretion in prepubertal gilts. The present data support the concept that kisspeptin plays a role in the mechanism involved in initiating puberty in swine.

Changes in growth rate and thyroid- and sex-hormones blood levels in rats under sub-chronic lithium treatment

2006 ◽  
Vol 25 (5) ◽  
pp. 243-250 ◽  
Author(s):  
M S Allagui ◽  
N Hfaiedh ◽  
C Vincent ◽  
F Guermazi ◽  
J-C Murat ◽  
...  
Keyword(s):  
Growth Rate ◽  
Lithium Treatment ◽  
Lithium Carbonate ◽  
Serum Levels ◽  
Antagonistic Effect ◽  
Blood Levels ◽  
Vaginal Mucosa ◽  
Dependent Manner ◽  
Serum Concentrations ◽  
Dose Dependent

Lithium therapy, mainly used in curing some psychiatric diseases, is responsible for numerous undesirable side effects. The present study is a contribution to the understanding of the pathophysiological mechanisms underlying lithium toxicity. Male and female mature rats were divided into three batches and fed commercial pellets: one batch was the control and the second and third batches were given 2 g (Li1) and 4 g (Li2) of lithium carbonate/kg of food/day, respectively. After 7, 14, 21 and 28 days, serum levels of free tri-iodothyronine (FT3), thyroxine (FT4), testosterone and estradiol were measured. Attention was also paid to growth rate and a histological examination of testes or vaginal mucosa was carried out. In treated rats, a dose-dependent loss of appetite and a decrease in growth rate were observed, together with symptoms of polydypsia, polyuria and diarrhea. Lithium serum concentrations increased from 0.44 mM (day 7) to 1.34 mM (day 28) in Li1 rats and from 0.66 to 1.45 mM (day 14) in Li2 rats. Li2 treatment induced a high mortality after 14 days, reaching 50-60% in female and male animals. From these data, the LD50 (14 days Li2 chronic treatment) was calculated to be about 0.3 g/day per kilogram of animal, leading to Li serum concentrations of about 1.4 mM. A significant decrease of FT3 and FT4 was observed in treated rats. This effect appeared immediately for the highest dose and was more pronounced for FT3, resulting in an increase of the FT4/FT3 ratio. In males, testosterone decreased and spermatogenesis was stopped. Conversely, in females, estradiol increased in a dose-dependent manner as the animals were blocked in the diestrus phase at day 28. This finding supports a possible antagonistic effect of lithium on the estradiol receptors.

Serotonin stimulates GH secretion through a direct pituitary action: studies in hypophysectomized autografted animals and in perifused pituitaries

1986 ◽  
Vol 113 (3) ◽  
pp. 317-322 ◽  
Author(s):  
F. López ◽  
D. Gónzalez ◽  
E. Aguilar
Keyword(s):  
Plasma Volume ◽  
Direct Action ◽  
Experimental Models ◽  
Male Rats ◽  
Blood Samples ◽  
Kidney Capsule ◽  
Gh Secretion ◽  
Significant Release ◽  
The Right ◽  
Dose Dependent

Abstract. To analyze a possible direct action of serotonin (5-hydroxytryptamine) at pituitary level in GH secretion, two experimental models were used: hypophysectomized autografted rats and perifused pituitaries. Adult male rats were hypophysectomized and their own pituitaries placed under the right kidney capsule. Ten days later an intra-atrial cannula was inserted. The next day, blood samples were obtained before and every 10 min during a 2 h period after the injection of saline or 5-hydroxytryptamin (1 or 2 mg/kg iv). Plasma volume was replaced with saline. Both doses of 5-hydroxytryptamine elicit a strong release of GH, the effect being dose-dependent. In pituitaries perifused with 5-hydroxytryptamine (100 μm during 115 min or 1, 10 and 100 μm during 15 min), a significant release of GH was also observed. These results suggested that 5-hydroxytryptamine may stimulate GH secretion through a direct pituitary action.

Growth hormone secretion in the guinea-pig

1990 ◽  
Vol 124 (3) ◽  
pp. 371-380 ◽  
Author(s):  
B. Gabrielsson ◽  
K. M. Fairhall ◽  
I. C. A. F. Robinson
Keyword(s):  
Growth Hormone ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Physiological Control ◽  
Gh Secretion ◽  
Dose Dependent Fashion ◽  
Growth Promoting ◽  
Dose Dependent

ABSTRACT The guinea-pig is unusual in that it continues to grow at a normal rate after hypophysectomy. Although its pituitary gland appears to contain a GH, this has not been isolated or characterized, and nothing is known about its secretion or physiological control. We have identified guinea-pig GH, established a sensitive heterologous radioimmunoassay and adapted our automatic blood microsampling method to study spontaneous GH secretion in this species. In male guinea-pigs, GH is released in an episodic pattern, reminiscent of the rat. Large multicomponent pulses of GH secretion occur every 3–4 h between periods of low or undetectable GH release, whereas most females showed a more uniform pulsatile pattern with pulses every 1–2 h. GH was released in response to GH-releasing factor (GRF) injections (2, 10 or 20 μg [Nle27]-GRF(1–29)NH2) in a dose-dependent fashion, and i.v. infusion of somatostatin (50 μg/h) blocked spontaneous GH pulses, eliciting a rebound release (from 2·0±0·8 (s.e.m.) to 36±17 μg/l 30 min after stopping the infusion). Infusions of a GH-releasing hexapeptide (100 or 400 μg/h for 4 h) also released GH. These results provide the first description of the pattern of GH release in the guinea-pig, and suggest that the striking episodic pattern is controlled by the same hypothalamic peptides that regulate GH in other species. Since the guinea-pig grows well in the absence of GH, this species may use GH for its metabolic, rather than growth-promoting actions. The guinea-pig may well prove a useful model, now that methods are available for studying its endogenous GH secretion. Journal of Endocrinology (1990) 124, 371–380

THE INFLUENCE OF GROWTH HORMONE TREATMENT ON THYROID FUNCTION IN SWINE

1990 ◽  
Vol 70 (3) ◽  
pp. 991-995 ◽  
Author(s):  
R. N. KIRKWOOD ◽  
P. A. THACKER ◽  
B. LAARVELD
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Key Words ◽  
Growth Hormone Treatment ◽  
Sampling Period ◽  
Hormone Treatment ◽  
Serum Concentrations ◽  
Significant Treatment ◽  
Blood Samples ◽  
To Receive

Twelve castrated male pigs of Yorkshire and Landrace breeding were selected at 95.9 ± 1.6 kg body weight (BW) and allocated equally to receive daily injections of either porcine growth hormone (pGH) at 90 μg kg−1 BW or vehicle buffer for four consecutive days. Following the last pGH injection, the pigs were infused via indwelling vena caval cannulae with thyrotropin-releasing hormone (TRH) at 0.5 μg kg−1 BW. Blood samples were obtained at 10 and 0 min before TRH and thereafter at 10-min intervals for 90 min. Serum concentrations of thyroxine and thyrotropin were lower (P < 0.06 and P < 0.1, respectively) but those of triiodothyronine higher (P < 0.01) in pGH-treated pigs throughout the sampling period. There were no significant treatment-by-time interactions indicating that the thyroid response to TRH was not influenced by pGH treatment. Key words: Swine, thyroid, growth hormone, somatotropin

Comparison of ramp and square-wave exposure to thyrotrophin-releasing hormone or depolarizing K+ on cytosolic Ca2+ concentration and prolactin secretion in GH4C1 cells

1994 ◽  
Vol 142 (1) ◽  
pp. 145-152
Author(s):  
N Sato ◽  
X Wang ◽  
M A Greer
Keyword(s):  
Hormone Secretion ◽  
Wave Exposure ◽  
Rate Of Change ◽  
Second Phase ◽  
Tissue Fluid ◽  
Dependent Manner ◽  
Thyrotrophin Releasing Hormone ◽  
Releasing Hormone ◽  
Square Wave ◽  
Dose Dependent

Abstract The standard method of studying hormone secretion in vitro is to make instantaneous changes in the concentration of stimulators in the medium. However, in vivo the extracellular concentration of such substances changes more gradually; secretion does not occur in square-wave bursts and agonists or antagonists transmitted through the bloodstream are diluted and diffused by plasma or tissue fluid to further decelerate the rate of change in concentration at the cell surface. We have therefore compared in GH4C1 cells the dynamics of changes in cytosolic Ca2+ concentration ([Ca2+]i) and prolactin (PRL) secretion in response to two very different secretagogues, thyrotrophin-releasing hormone (TRH) and depolarizing K+, using a square-wave or ramp exposure for 5 min. The dynamics of hormone secretion were analysed by column perifusion (2 × 106 cells/column). Ca2+ dynamics were monitored by dual excitation microfluorimetry from 20–30 optically isolated cells using the Ca2+ indicator, fura-2. With square-wave exposure, both TRH (0·1–100 nm) and K+ (10–50 mm) induced dose-dependent increases in [Ca2+]i and PRL secretion. Concentrations of TRH >1 nm caused a two-phase increase in [Ca2+]i with an initial high-amplitude first phase and a low-amplitude second phase. Depolarizing K+ induced a sharp increase in [Ca2+]i which peaked within 15 seconds, then declined gradually on a sloping plateau. Both TRH and K+ induced an acute dose-dependent PRL secretory burst peaking within 2·5 min with a subsequent rapid decline. With ramp exposure, high doses of TRH (final concentration 10–100 nm) triggered an acute rise in [Ca2+]i; however, the peaks were clearly lower than those induced by the maximum concentration reached given as a square-wave. TRH (0·1–100 nm) induced PRL secretion in a dose-dependent manner. Ramp depolarizing K+ induced dose-dependent parallel 'ramp' increases in [Ca2+]i concentration and PRL secretion without a 'burst' rise in either. These data suggest that a rise in [Ca2+]i plays a more critical role in K+-induced than in TRH-induced PRL secretion; intracellular transduction systems which do not involve [Ca2+]i appear more important for the latter. Journal of Endocrinology (1994) 142, 145–152

Randomized, Dose-Escalation Study of SD/01 Compared With Daily Filgrastim in Patients Receiving Chemotherapy

2000 ◽  
Vol 18 (13) ◽  
pp. 2522-2528 ◽  
Author(s):  
Eileen Johnston ◽  
Jeffrey Crawford ◽  
Susan Blackwell ◽  
Toni Bjurstrom ◽  
Pamela Lockbaum ◽  
...  
Keyword(s):  
Self Regulation ◽  
Clinical Settings ◽  
Serum Concentrations ◽  
Dose Escalation Study ◽  
Significant Toxicity ◽  
Dose Dependent Fashion ◽  
Chemotherapy Induced Neutropenia ◽  
Cell Mobilization ◽  
To Receive ◽  
Dose Dependent

PURPOSE: To explore the use of SD/01 (a polyethylene glycol–conjugated filgrastim shown in preclinical studies to have a prolonged half-life) in patients with chemotherapy-induced neutropenia. PATIENTS AND METHODS: Thirteen patients with non–small-cell lung cancer were randomized to receive daily filgrastim (5 μg/kg/d) or a single injection of SD/01 (30, 100, or 300 μg/kg) 2 weeks before chemotherapy and again 24 hours after administration of carboplatin and paclitaxel. Pharmacodynamic, pharmacokinetic, and safety analyses were performed. RESULTS: Peak serum concentrations of SD/01 and the duration of increased serum concentrations were dependent on the SD/01 dose. SD/01 concentrations remained increased longer in patients with chemotherapy-induced neutropenia. Prechemotherapy median absolute neutrophil counts (ANCs) in patients receiving SD/01 were increased in a dose-dependent fashion, with the duration of this effect also being dose dependent. After chemotherapy, median ANC nadirs were similar in the filgrastim cohort and the cohort receiving SD/01 30 μg/kg, with higher nadirs seen in the cohorts receiving SD/01 100 or 300 μg/kg. Dose-limiting toxicities were not noted. CD34+ cells were mobilized in all cohorts. CONCLUSION: A single dose of SD/01 increases the serum concentration of SD/01 for several days in a dose-dependent fashion and is not associated with significant toxicity. The effects of SD/01 on ANC and CD34+ cell mobilization are comparable or greater than those achieved with daily filgrastim. The self-regulation of this molecule provides a potential therapeutic advantage in a variety of clinical settings associated with neutropenia.

Lipopolysaccharide induces fever and depresses locomotor activity in unrestrained mice

1994 ◽  
Vol 266 (1) ◽  
pp. R125-R135 ◽  
Author(s):  
W. Kozak ◽  
C. A. Conn ◽  
M. J. Kluger
Keyword(s):  
Locomotor Activity ◽  
Food Intake ◽  
Body Temperature ◽  
Guinea Pigs ◽  
Time Course ◽  
Laboratory Animals ◽  
Dependent Manner ◽  
Basic Biology ◽  
Freely Moving ◽  
Dose Dependent

The purpose of this study was to characterize the basic biology of fever to lipopolysaccharide (LPS) in unrestrained mice. Although LPS has been shown to induce fevers in many laboratory animals (e.g., rats, guinea pigs, rabbits), there is some question of whether LPS causes a fall or rise in body temperature (Tb) in mice. Tb was measured by biotelemetry in unrestrained mice maintained at an ambient temperature of 30 degrees C. Intraperitoneal injections of LPS at doses of 1.0, 2.5, and 3.0 mg/kg induced dose-independent prompt decreases of Tb for 5.7 h. After this postinjection reduction, Tb increased and reached a peak at approximately 24 h postinjection. The peak rises in Tb were dose dependent. Changes in Tb due to LPS were accompanied by suppression of locomotor activity. Indomethacin, at a dose that did not affect normal Tb, enhanced the temperature-lowering effect of LPS as well as inhibited the febrile rise of Tb after LPS. Indomethacin did not modify the reduction in activity caused by the injections of LPS. Food intake of the mice was decreased by LPS in a dose-dependent manner, and tolerance developed to a second injection of LPS. We conclude that freely moving mice can develop pronounced and reproducible fevers in response to LPS, which is different in time course, dose-dependent profile, induction of pyrogenic tolerance profile, and mode of inhibition by indomethacin from those responses that have been observed in other species studied so far.

Trypsinization of bovine parathyroid cells abolishes Ca2+-regulated parathyroid hormone secretion

1989 ◽  
Vol 122 (1) ◽  
pp. 213-218 ◽  
Author(s):  
R. Muff ◽  
J. A. Fischer
Keyword(s):  
Protein Kinase C ◽  
Parathyroid Hormone ◽  
Protein Kinase ◽  
Adrenergic Receptors ◽  
Hormone Secretion ◽  
Dependent Manner ◽  
Kinase C ◽  
And Control ◽  
Β Adrenergic Receptors ◽  
Dose Dependent

ABSTRACT The secretion of parathyroid hormone (PTH) is inversely related to the extracellular Ca2+ concentration (Cae2+). To test the hypothesis that a Ca2+ sensor on the surface of parathyroid cells is involved in Ca2+-regulated PTH secretion, limited trypsinization of bovine parathyroid cells was carried out. Treatment with trypsin (1·1–10 mg/ml) inhibited, in a dose-dependent manner, PTH secretion stimulated by lowering Cae2+ from 2·0 to 0·5 mmol/l. In control cells, activation of protein kinase C with 12-O-tetradecanoylphorbol-13-acetate (TPA) enhanced PTH secretion at 2·0 mmol Cae2+/1 but not at 0·5 mmol Cae2+/1. In trypsinized cells, however, TPA enhanced PTH secretion at both 0·5 and 2·0 mmol Cae2+/1. Isoproterenol-stimulated PTH secretion was maintained in trypsinized cells, but reduced cyclic AMP production revealed that some β-adrenergic receptors were destroyed. The cytosolic free Ca2+ concentration (Cai2+), as measured with fura-2, was raised within seconds in response to increasing Cae2+ from 0·5 to 2·0 mmol/l and was then lowered within 1 min to a sustained plateau; the changes were the same in trypsinized and control cells. In conclusion, trypsinization of parathyroid cells abolished Ca2+-regulated PTH secretion without affecting Cai2+. Journal of Endocrinology (1989) 122, 213–218

Interleukin 6 inhibits human thyroid peroxidase gene expression

1991 ◽  
Vol 124 (3) ◽  
pp. 290-294 ◽  
Author(s):  
Tan Tominaga ◽  
Shunichi Yamashita ◽  
Yuji Nagayama ◽  
Shigeki Morita ◽  
Naokata Yokoyama ◽  
...  
Keyword(s):  
Gene Expression ◽  
Interleukin 6 ◽  
Interleukin 1 ◽  
Hormone Secretion ◽  
Interferon Γ ◽  
Human Thyroid ◽  
Thyroid Peroxidase ◽  
Dependent Manner ◽  
Human Thyroid Peroxidase ◽  
Dose Dependent

Abstract. It has been reported that cytokines, especially interleukin 1 and interferon-γ, inhibit the thyroid hormone secretion and the gene expression of human thyroid peroxidase and thyroglobulin. Interleukin 6 has recently been found to be an important cytokine for the regulation of immunoendocrine interaction and intrathyroidal production of interleukin 6 has been reported. Therefore, we investigated the regulation of thyroid hormone secretion and thyroid peroxidase messenger RNA by interleukin 6 in human thyrocytes to clarify further the functional role of interleukin 6 in thyroid glands. Thyrocytes dispersed from Graves' thyroid tissues were incubated with TSH with or without interleukin 6. TSH (5 U/l stimulated the expression of thyroid peroxidase mRNA transcripts (4.0, 3.2, 2.1, and 1.7 kb, respectively), although unstimulated thyrocytes contained the low level of 3.2 kb thyroid peroxidase mRNA transcript. Interleukin 6 (104-105 U/l) inhibited TSH-induced thyroid peroxidase mRNA in a dose-dependent manner, although the basal level of thyroid peroxidase mRNA expression was not suppressed by interleukin 6. Interleukin 6 also inhibited 8-bromo-cyclic adenosine monophosphate-induced thyroid peroxidase mRNA levels. In contrast, the γ-action mRNA hybridization signal was not altered in control or treated cells. Subsequently, interleukin 6 inhibited TSH-induced T3 secretion in a dose-dependent manner after 72 h treatment. However, interleukin 6 did not affect DNA synthesis. Pretreatment with specific antibody against interleukin 6 selectively restored the inhibitory effect of interleukin 6 on thyroid peroxidase gene expression. Our results suggest that interleukin 6 plays an inhibitory role in the thyroid gland, in addition to interleukin 1 and interferon γ.

scholarly journals Development and Validation of a Quantitative UHPLC-MS/MS Method for the Determination of Alpha-Chloralose in Feline Blood and Application on Blood Samples Collected From Cats With Symptoms of Alpha-Chloralose Poisoning

2021 ◽  
Author(s):  
Ulrika Windahl ◽  
Sandra Lundgren ◽  
Margareta Sprycha ◽  
Cecilia Tegner ◽  
Kristoffer Dreimanis ◽  
...  
Keyword(s):  
Limit Of Detection ◽  
Anaesthetic Agent ◽  
Domestic Animals ◽  
Laboratory Animals ◽  
Limit Of Quantification ◽  
Blood Samples ◽  
Body Tissues ◽  
Alpha Chloralose ◽  
Development And Validation ◽  
Clinical Cases

Abstract Alpha-chloralose (AC) is used as a rodenticide as well as an anaesthetic agent in laboratory animals. It was previously also used as an avicide. Detection of AC in blood samples or post-mortem in body tissues is key for diagnosis of clinical cases and a requirement for surveillance of secondary toxicosis, including potential cases in wild animals. Reports on poisoning of humans and non-laboratory animals confirmed by detection of AC or its metabolites are available, although rarely on domestic animals. Furthermore, reports on clinical cases in domestic animals rarely report quantifications of AC in blood or body tissues. The present study describes the validation of a quantitative UHPLC-MS/MS method that can be used in cases of suspected AC poisoning in cats. The validation study showed the method to be fit for purpose. In serum the limit of quantification was 100 ng/mL and the limit of detection 30 ng/mL. The new analytical method was applied on blood samples collected from 20 individual cats with a preliminary clinical diagnosis of acute AC poisoning. Alpha-chloralose was confirmed in all 20 feline blood samples, and the concentration range of AC was 538 -17 500 ng/mL. The quantitative method developed in this study was found to be a fast and selective method for confirmation of AC poisoning using blood samples from cats.

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