Direct pituitary inhibition of prolactin secretion by dopamine and noradrenaline in sheep

1989 ◽  
Vol 123 (3) ◽  
pp. 393-402 ◽  
Author(s):  
G. B. Thomas ◽  
J. T. Cummins ◽  
B. W. Doughton ◽  
N. Griffin ◽  
G. A. Smythe ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Prolactin Secretion ◽  
Plasma Prolactin ◽  
Dependent Manner ◽  
Dopamine Receptor Antagonist ◽  
Peripheral Plasma ◽  
Series Of Experiments ◽  
Dose Dependent ◽  
Inhibitory Regulation ◽  
Sustained Increase

ABSTRACT The effects of dopamine, noradrenaline and 3,4-dihydroxyphenylacetic acid (DOPAC) on the release of prolactin were examined in ovariectomized ewes. Infusion of dopamine (0·5 or 1 μg/kg per min for 2 h i.v.) reduced plasma prolactin concentrations in a dose-dependent manner, whereas DOPAC (5 or 10 μg/kg per min for 2 h i.v.) had no effect. In a further series of experiments, ovariectomized hypothalamo-pituitary disconnected ewes were given dopamine or noradrenaline (each at 0·5 or 1 μg/kg per min for 2 h i.v.), and both amines reduced mean plasma concentrations of prolactin with similar potency in a dose-dependent manner. These effects were blocked by treatment with pimozide and prazosin respectively. During the infusion of dopamine, the peripheral plasma concentrations of DOPAC and 3,4-dihydroxyphenylethyleneglycol (DHPG) were increased (DOPAC, 22 ± 7 (s.e.m.) to 131 ± 11 nmol/l; DHPG, 2·9 ± 0·3 to 6·4 ± 0·2 nmol/l), but plasma concentrations of dopamine and noradrenaline did not change. Finally, administration of domperidone, a specific dopamine receptor antagonist that does not cross the blood-brain barrier, resulted in a sustained increase in plasma prolactin concentrations in ovariectomized ewes. We conclude that the secretion of prolactin from the pituitary gland is under dual inhibitory regulation by both dopamine and noradrenaline in the sheep. Journal of Endocrinology (1989) 123, 393–402

Role of extracellular calcium and calmodulin in prolactin secretion induced by hyposmolarity, thyrotropin-releasing hormone, and high K+ in GH4C1 cells

1990 ◽  
Vol 123 (2) ◽  
pp. 218-224 ◽  
Author(s):  
Xiangbing Wang ◽  
Noriyuki Sato ◽  
Monte A. Greer ◽  
Susan E. Greer ◽  
Staci McAdams
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxant ◽  
Prolactin Secretion ◽  
Thyrotropin Releasing Hormone ◽  
Dependent Manner ◽  
Cell Toxicity ◽  
High K ◽  
Dose Dependent ◽  
Smooth Muscle Relaxant

Abstract. The mechanism by which 30% medium hyposmolarity induces PRL secretion by GH4C1 cells was compared with that induced by 100 nmol/l TRH or 30 mmol/l K+. Removing medium Ca2+, blocking Ca2+ channels with 50 μmol/l verapamil, or inhibiting calmodulin activation with 20 μmol/l trifluoperazine, 10 μmol/l chlorpromazine or 10 μmol/l pimozide almost completely blocked hyposmolarity-induced secretion. The smooth muscle relaxant, W-7, which is believed relatively specific in inhibiting the Ca2+-calmodulin interaction, depressed hyposmolarity-induced PRL secretion in a dose-dependent manner (r = −0.991, p<0.01 ). The above drugs also blocked or decreased high K+-induced secretion, but had much less effect on TRH-induced secretion. Secretion induced by TRH, hyposmolarity, or high K+ was optimal at pH 7.3-7.65 and was significantly depressed at pH 6.0 or 8.0, indicating that release of hormone induced by all 3 stimuli is due to an active cell process requiring a physiologic extracellular pH and is not produced by nonspecific cell toxicity. The data suggest hyposmolarity and high K+ may share some similarities in their mechanism of stimulating secretion, which is different from that of TRH.

scholarly journals Biochanin A, the Most Potent of 16 Isoflavones, Induces Relaxation of the Coronary Artery Through the Calcium Channel and cGMP-dependent Pathway

Planta Medica ◽  
2020 ◽  
Vol 86 (10) ◽  
pp. 708-716
Author(s):  
Thomas Migkos ◽  
Jana Pourová ◽  
Marie Vopršalová ◽  
Cyril Auger ◽  
Valérie Schini-Kerth ◽  
...  
Keyword(s):  
Coronary Arteries ◽  
Mechanism Of Action ◽  
Biochanin A ◽  
Dependent Manner ◽  
Major Mechanism ◽  
Camp Pathway ◽  
Clinical Interest ◽  
Series Of Experiments ◽  
Dose Dependent ◽  
Dependent Pathway

AbstractThe dietary intake of flavonoids seems to be inversely related to cardiovascular mortality. The consumption of isoflavonoids is increasing in the general population, especially due to the use of food supplements and a variety of isoflavonoid-rich foods. However, detailed studies on the vascular influence of individual pure isoflavonoids are mostly missing. For this study, 16 isoflavonoids were initially screened for their vasorelaxant properties on rat aortas. The 2 most potent of them, biochanin A and glycitein, were further tested for the mechanism of action on porcine coronary arteries. They both induced an endothelium independent vascular relaxation, with EC50 below 6 and 17 µM, respectively. Biochanin A, but not glycitein, was able to block the vasoconstriction caused by KCl, CaCl2, serotonin, and U46619 in a dose-dependent manner. Another series of experiments suggested that the major mechanism of action of biochanin A was the inhibition of L-type calcium channels. Moreover, biochanin A in relatively small concentrations (2 – 4 µM) interfered with the cGMP, but not cAMP, pathway in isolated coronary arteries. These results indicate that some isoflavonoids, in particular biochanin A, are able to have vasodilatory effects in micromolar concentrations, which is of potential clinical interest for the management of cardiovascular pathologies.

scholarly journals Seasonal effects of central leptin infusion on secretion of melatonin and prolactin and on SOCS-3 gene expression in ewes

2008 ◽  
Vol 198 (1) ◽  
pp. 147-155 ◽  
Author(s):  
D A Zieba ◽  
M Szczesna ◽  
B Klocek-Gorka ◽  
E Molik ◽  
T Misztal ◽  
...  
Keyword(s):  
Third Ventricle ◽  
Plasma Concentrations ◽  
Seasonal Effects ◽  
Cytokine Signaling ◽  
Dependent Manner ◽  
Suppressor Of Cytokine Signaling ◽  
Medial Basal Hypothalamus ◽  
Leptin Sensitivity ◽  
Dose Dependent ◽  
Short Days

Recent studies have demonstrated photoperiodic changes in leptin sensitivity of seasonal mammals. Herein, we examined the interaction of season (long days (LD) versus short days (SD)) and recombinant ovine leptin (roleptin) on secretion of melatonin and prolactin (PRL) and on mRNA expression of suppressor of cytokine signaling-3 (SOCS-3) in the medial basal hypothalamus (MBH) in sheep. Twenty-four Polish Longwool ewes, surgically fitted with third ventricle (IIIV) cannulas, were utilized in a replicated switchback design involving 12 ewes per season. Within-season and replicate ewes were assigned randomly to one of three treatments (four ewes/treatment) and infused centrally three times at 0, 1 and 2 h beginning at sunset. Treatments were 1) control, Ringer–Locke buffer; 2) L1, roleptin, 0.5 μg/kg BW; and 3) L2, roleptin, 1.0 μg/kg BW. Jugular blood samples were collected at 15-min intervals beginning immediately before the start of infusions and continued for 6 h. At the end of blood sampling, a washout period of at least 3 days elapsed before ewes were re-randomized and treated with one of the treatments described above (four ewes/treatment). Ewes were then killed and brains were collected for MBH processing. Leptin treatments increased (P<0.001) circulating leptin concentrations compared with controls during both seasons in a dose-dependent manner. Overall, mean plasma concentrations of melatonin were greater (P<0.001) during LD than SD. However, leptin treatments increased melatonin concentrations during SD in a dose-dependent manner and decreased it during LD. Similarly, plasma concentrations of PRL were greater (P<0.001) during LD than SD. However, unlike changes in melatonin, circulating PRL decreased (P<0.001) in response to leptin during LD. Semi-quantitative PCR revealed that leptin increased (P<0.001) SOCS-3 expression in the MBH region during LD in a dose-dependent manner. Data provide evidence that secretion of photoperiodic hormones such as melatonin and PRL are inversely regulated by leptin during SD and LD. However, the increase in expression of SOCS-3 in the MBH during LD compared with SD fails to fully explain these effects.

Voluntary running of defined distances reduces body adiposity and its associated inflammation in C57BL/6 mice fed a high-fat diet

2017 ◽  
Vol 42 (11) ◽  
pp. 1179-1184 ◽  
Author(s):  
Lin Yan ◽  
Sneha Sundaram ◽  
Forrest H. Nielsen
Keyword(s):  
High Fat Diet ◽  
Plasma Concentrations ◽  
Standard Diet ◽  
Dependent Manner ◽  
High Fat ◽  
Body Adiposity ◽  
Chemotactic Protein ◽  
Voluntary Running ◽  
Significant Difference ◽  
Dose Dependent

This study investigated the effect of voluntary running of defined distances on body adiposity in male C57BL/6 mice fed a high-fat diet. Mice were assigned to 6 groups and fed a standard AIN93G diet (sedentary) or a modified high-fat AIN93G diet (sedentary; unrestricted running; or 75%, 50%, or 25% of unrestricted running) for 12 weeks. The average running distance was 8.3, 6.3, 4.2, and 2.1 km/day for the unrestricted, 75%, 50%, and 25% of unrestricted runners, respectively. Body adiposity was 46% higher in sedentary mice when fed the high-fat diet instead of the standard diet. Running decreased adiposity in mice fed the high-fat diet in a dose-dependent manner but with no significant difference between sedentary mice and those running 2.1 km/day. In sedentary mice, the high-fat instead of the standard diet increased insulin resistance, hepatic triacylglycerides, and adipose and plasma concentrations of leptin and monocyte chemotactic protein-1 (MCP-1). Running reduced these variables in a dose-dependent manner. Adipose adiponectin was lowest in sedentary mice fed the high-fat diet; running raised adiponectin in both adipose tissue and plasma. Running 8.3 and 6.3 km/day had the greatest, but similar, effects on the aforementioned variables. Running 2.1 km/day did not affect these variables except, when compared with sedentariness, it significantly decreased MCP-1. The findings showed that running 6.3 kg/day was optimal for reducing adiposity and associated inflammation that was increased in mice by feeding a high-fat diet. The findings suggest that voluntary running of defined distances may counteract the obesogenic effects of a high-fat diet.

Reversal of Dabigatran's Anticoagulant Activity in the Monkey by a Specific Antidote and Pharmacokinetic and Pharmacodynamic Modeling

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 22-22 ◽  
Author(s):  
Joshuaine Toth ◽  
Guanfa Gan ◽  
Joanne van Ryn ◽  
Holly Dursema ◽  
Jennifer Isler ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Anticoagulant Activity ◽  
Plasma Concentrations ◽  
Mass Action ◽  
Pharmacodynamic Modeling ◽  
Dependent Manner ◽  
Thrombin Time ◽  
Binding Interaction ◽  
Mass Action Kinetics ◽  
Dose Dependent

Abstract Abstract 22 Background: The objective of this study is to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of dabigatran (a small molecule thrombin inhibitor) and its antidote (a humanized Fab against dabigatran) in the monkey and to develop a combined mechanistic mathematical model to describe the data. Methods: There were three groups: control, antidote alone and dabigatran etexilate (DE) + antidote. Rhesus monkeys (n = 2/group) received either 12 mg/kg/day of DE or vehicle orally on Days 1–4, 15–18 and 29–32 with a single IV dose of the antidote administered 90 minutes after DE on Days 4, 18 and 32. Doses of the antidote were 30, 90 or 175 mg/kg, respectively. PK parameters of the antidote and sum dabigatran (dabigatran plus its glucuronides) were determined after measurements of plasma concentrations. Coagulation activity was measured using a diluted thrombin time assay to determine the activity of the unbound sum dabigatran. Results: The PK of the antidote were not affected by dabigatran. Clearance of the antidote was low (0.87 mL/min/kg) and steady-state volume of distribution was small (0.06 L/kg), indicating that the antidote was mostly restricted to plasma. The plasma profile of the antidote was bi-phasic with a short initial phase t1/2 of 0.4 hour (h) and a terminal phase t1/2 of 4.3 h. Immediately after antidote dosing, plasma concentrations of sum dabigatran increased, a consequence of the rapid redistribution of dabigatran and its glucuronides from tissue to plasma due to binding to the antidote. Complete reversal of dabigatran's anticoagulant activity was observed immediately after antidote dosing at all three dose levels, as measured by the diluted thrombin time assay, which indicates that all dabigatran was bound to the antidote. The degree to which this reversal effect was maintained over an extended period (24 h) was dose-dependent. A mechanistic ordinary differential equation model, based on the mass action kinetics for describing the distribution, binding and elimination of dabigatran and its antidote, was developed by combining the PK models for dabigatran and the antidote and adding the binding interaction (1:1 stoichiometry) between the two compounds. The distribution and elimination parameters of the dabigatran-antidote complex were assumed to be the same as those of the antidote, based on similar measured PK parameters of the antidote with and without dabigatran in the monkey. The combined PK/PD model of dabigatran and antidote was able to describe the in vivo PK/PD data observed in monkeys. Conclusion: The dabigatran-specific antidote successfully reversed the anticoagulant activity of dabigatran in the monkey in a dose-dependent manner, and our combined mathematical model accurately describes monkey PK/PD data of sum dabigatran and its antidote. Insights gained from this model will be used to guide model development for clinical trials. Disclosures: Toth: Boehringer Ingelheim: Employment. Gan:Boehringer Ingelheim: Employment. van Ryn:Boehringer Ingelheim: Employment. Dursema:Boehringer Ingelheim: Employment. Isler:Boehringer Ingelheim: Employment. Coble:Boehringer Ingelheim: Employment. Burke:Boehringer Ingelheim: Employment. Lalovic:Boehringer Ingelheim: Employment. Olson:Boehringer Ingelheim: Employment.

A neuroendocrine model for prolactin as the key mediator of seasonal breeding in birds under long- and short-day photoperiods

2003 ◽  
Vol 81 (4) ◽  
pp. 350-358 ◽  
Author(s):  
Peter J Sharp ◽  
Dominique Blache
Keyword(s):  
Breeding Season ◽  
Plasma Concentrations ◽  
Prolactin Secretion ◽  
Gonadotropin Releasing Hormone ◽  
Critical Threshold ◽  
Plasma Prolactin ◽  
Seasonal Breeding ◽  
Releasing Hormone ◽  
Short Day ◽  
Long Day

Seasonal breeding is associated with sequential increases in plasma luteinizing hormone (LH) and prolactin in the short-day breeding emu, and in long-day breeding birds that terminate breeding by the development of reproductive photorefractoriness. A model of the avian neuroendocrine photoperiodic reproductive response is proposed, incorporating a role for prolactin, to account for neuroendocrine mechanisms controlling both long- and short-day breeding. The breeding season terminates after circulating concentrations of prolactin increase above a critical threshold to depress gonadotropin releasing hormone (GnRH) neuronal and gonadotrope (LH) activity. Subsequently, photorefractoriness develops for prolactin secretion and for LH secretion, independently of high plasma prolactin. The breeding season in the emu is advanced compared with long-day breeders, because after photorefractiness for both LH and prolactin secretion is dissipated, plasma concentrations of both hormones increase to maximum values while days are still short.Key words: seasonal breeding, prolactin, gonadotropin releasing hormone, photorefactoriness.

Involvement of the adrenal gland in the suckling-induced decrease in LH and FSH secretion and the concomitant increase in prolactin secretion in the rat

1990 ◽  
Vol 125 (2) ◽  
pp. 279-285 ◽  
Author(s):  
K. Taya ◽  
S. Sasamoto
Keyword(s):  
Adrenal Gland ◽  
Ovarian Function ◽  
Plasma Concentrations ◽  
Prolactin Secretion ◽  
Plasma Prolactin ◽  
Luteal Function ◽  
Follicular Maturation ◽  
High Concentrations ◽  
Ovulatory Follicles

ABSTRACT The role of the adrenal gland in the regulation of gonadotrophin and prolactin secretion in the lactating rat was investigated. Changes in secretion of LH, FSH, prolactin, ACTH, β-lipotrophin (β-LPH), inhibin, corticosterone and progesterone after adrenalectomy were examined during the second half of lactation. Follicular maturation was determined by the ability of the follicles to ovulate in response to 10IU human chorionic gonadotrophin (hCG). Adrenalectomy on day 10 of lactation prevented an increase in plasma concentrations of LH and FSH in response to ovariectomy performed at the same time as adrenalectomy, and markedly stimulated secretion of ACTH, β-LPH and prolactin. Adrenalectomy reduced the number of follicles capable of ovulating in response to hCG. Concentrations of inhibin and progesterone in the plasma significantly decreased after adrenalectomy, indicating that development of ovulatory follicles and luteal function had been suppressed. Abolishing the increase in plasma concentrations of LH and inducing a decrease in FSH in the plasma by adrenalectomy therefore prevented maturation of a new set of follicles usually seen during the second half of lactation in rats. The decrease in plasma concentrations of LH also inhibited the ability of the corpus luteum to secrete progesterone, although high concentrations of plasma prolactin were maintained in adrenalectomized lactating rats. These results indicate that the pituitary-adrenal system is capable of influencing the maintenance of a normal secretion of gonadotrophin and prolactin as well as the maintenance of ovarian function during lactation in the rat. Journal of Endocrinology (1990) 125, 279—285

EFFECT OF RESERPINE ON PLASMA CONCENTRATIONS OF GROWTH HORMONE AND PROLACTIN IN THE DOMESTIC FOWL

1978 ◽  
Vol 79 (1) ◽  
pp. 153-154 ◽  
Author(s):  
S. HARVEY ◽  
C. G. SCANES ◽  
A. CHADWICK ◽  
N. J. BOLTON
Keyword(s):  
Growth Hormone ◽  
New Jersey ◽  
New Brunswick ◽  
Biogenic Amines ◽  
Domestic Fowl ◽  
Plasma Concentrations ◽  
Prolactin Secretion ◽  
Peripheral Plasma ◽  
Rutgers University

Department of Zoology, University of Hull, Hull, HU6 7RX, * Department of Physiology, Rutgers University, New Brunswick, New Jersey 08903, U.S.A. and †Department of Pure and Applied Zoology, University of Leeds, Leeds, LS2 9JT (Received 9 June 1978) It has been established that biogenic amines are involved in control of the secretion of prolactin (MacLeod, 1976) and growth hormone (GH; Martin, 1976) in mammals. In birds there is very little evidence for this, although in the domestic fowl it has recently been demonstrated that sytemically administered catecholamines (adrenaline and noradrenaline) markedly lower the concentration of GH in the peripheral plasma (Harvey & Scanes, 1978) and that serotonin stimulates the release of prolactin from incubated hemipituitary glands (Border & Chadwick, 1977). Therefore, to elucidate further the possible involvement of biogenic amines in the regulation of GH and prolactin secretion, the effect of reserpine (a 5-hydroxytryptamine- and catecholamine-depleting agent) on the concentrations

Role of the adrenal cortex in chronic stress-induced inhibition of prolactin secretion in male rats

1989 ◽  
Vol 120 (2) ◽  
pp. 269-273 ◽  
Author(s):  
A. López-Calderón ◽  
C. Ariznavarreta ◽  
M. D. Calderón ◽  
J. A. F. Tresguerres ◽  
M. I. Gonzalez-Quijano
Keyword(s):  
Adrenal Cortex ◽  
Chronic Stress ◽  
Immobilization Stress ◽  
Plasma Concentrations ◽  
Inhibitory Effect ◽  
Prolactin Secretion ◽  
Male Rats ◽  
Prolonged Release ◽  
Plasma Prolactin

ABSTRACT The response of prolactin to chronic stress in intact, adrenalectomized and adrenomedullectomized male rats was studied. Immobilization stress in intact animals induced a significant increase in plasma concentrations of prolactin after 20 and 45 min and a significant decrease when the rats were submitted to chronic restraint (6 h daily for 4 days). Five weeks after adrenomedullectomy, plasma prolactin and corticosterone responses to chronic stress were not modified. In contrast, the inhibitory effect of chronic stress on prolactin secretion was totally suppressed by adrenalectomy. When treated with dexamethasone during the 4 days of restraint, adrenalectomized stressed rats showed similar plasma concentrations of prolactin to the intact stressed rats. These data indicate that the adrenal cortex is able to play an inhibitory role on prolactin secretion during stress only through a prolonged release of glucocorticoids. Journal of Endocrinology (1989) 120, 269–273

Probucol Slows the Progression of Cataracts in Streptozotocin-Induced Hyperglycemic Rats

Pharmacology ◽  
2019 ◽  
Vol 103 (3-4) ◽  
pp. 212-219 ◽  
Author(s):  
Kentaro Higashi ◽  
Asami Mori ◽  
Kenji Sakamoto ◽  
Kunio Ishii ◽  
Tsutomu Nakahara
Keyword(s):  
Horizontal Plane ◽  
Plasma Concentrations ◽  
Antioxidant Properties ◽  
Digital Camera ◽  
Lipid Lowering ◽  
Protein Carbonyls ◽  
Dependent Manner ◽  
Cataract Formation ◽  
Camera System ◽  
Dose Dependent

We examined the effect of probucol, an antihyperlipidemic drug with potent antioxidant properties, on cataract formation in streptozotocin (STZ)-induced hyperglycemic rats that were given 5% D-glucose as drinking water. Probucol treatment was initiated immediately after the induction of hyperglycemia was confirmed. Using full horizontal-plane lens images captured with an original digital camera system, the opacity of central region of lens was assessed by measuring the opaque area in the region. Central opacities were detected after 3 weeks of hyperglycemia, and progressed in a time-dependent manner. The majority of STZ-induced hyperglycemic rats developed severe cataracts after 9 weeks of hyperglycemia. Probucol slowed the progression of cataracts in a dose-dependent manner. Levels of sorbitol and protein carbonyls in lenses of STZ-induced hyperglycemic rats were higher than those of control rats. Probucol suppressed the increase in protein carbonyls, but not of sorbitol, in lenses of STZ-induced hyperglycemic rats. Probucol had no significant effect on increases in plasma concentrations of glucose, total cholesterol, and triglyceride observed in STZ-induced hyperglycemic rats. These results suggest that probucol slows the progression of sugar cataracts, independent of its lipid-lowering effects. The beneficial effect of probucol on cataracts is partially attributable to the attenuation of oxidative damage to lens proteins.

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