Inhibitory effects of corticotrophin-releasing factor and β-endorphin on LH and FSH secretion in the lactating rat

1989 ◽  
Vol 120 (3) ◽  
pp. 509-515 ◽  
Author(s):  
K. Taya ◽  
S. Sasamoto
Keyword(s):  
Plasma Concentration ◽  
Opioid Peptides ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Rapid Decrease ◽  
Significant Decline ◽  
Plasma Prolactin ◽  
Inhibitory Effects ◽  
Corticotrophin Releasing Factor ◽  
Significant Change

ABSTRACT The roles of corticotrophin-releasing factor (CRF) and β-endorphin in the suppression of LH and FSH secretion during lactation were investigated using ovariectomized lactating rats separated from their litters overnight. Within 1 h of returning the pups to their mothers a marked fall in plasma LH concentration and a large increase in plasma prolactin were noted. However, resuckling caused no significant change in plasma concentration of FSH until 12 h after the return of the litter but a significant decline occurred thereafter. Twenty-four hours after removal of the litter, a single i.v. injection of 200 μl anti-LHRH serum caused similar changes in plasma concentrations of LH and FSH observed in nursing rats during suckling. These results suggest that the suckling stimulus itself is responsible for the suppression of LH as well as FSH, via inhibition of the secretion of LHRH. Twenty-four hours after removal of the litter, a single intracerebroventricular (i.c.v.) injection of either 10 μg CRF or β-endorphin resulted in a rapid decrease in plasma LH. Only β-endorphin caused a marked increase in plasma levels of prolactin within 1 h whereas FSH was less affected by either hormone. Repeated i.c.v. administration of 10 μg CRF or β-endorphin at 6-h intervals caused a prolonged inhibition of LH as well as FSH secretion during 48 h, with β-endorphin being less effective than CRF. These results demonstrate that the suckling stimulus alone suppressed the secretion of both LH and FSH, and suggest that this effect may be mediated by the inhibition of LHRH secretion from the hypothalamus. They also suggest that the suckling-induced inhibition of LHRH may be primarily mediated by endogenous CRF and opioid peptides. Journal of Endocrinology (1989) 120, 509–515

Regulation of the seasonal cycle of β-endorphin and ACTH secretion into the peripheral blood of rams

1990 ◽  
Vol 124 (3) ◽  
pp. 443-454 ◽  
Author(s):  
E. Ssewannyana ◽  
G. A. Lincoln ◽  
E. A. Linton ◽  
P. J. Lowry
Keyword(s):  
Plasma Concentration ◽  
Pituitary Gland ◽  
Plasma Levels ◽  
Seasonal Cycle ◽  
Plasma Concentrations ◽  
Pituitary Hormones ◽  
Similar Treatment ◽  
Corticotrophin Releasing Factor ◽  
Differential Control ◽  
Autumn And Winter

ABSTRACT In a group of 12 adult Soay rams living outdoors near Edinburgh there was a conspicuous seasonal cycle in the peripheral plasma concentrations of β-endorphin, ACTH and cortisol. The concentration of all three hormones increased 5- to 20-fold from winter to summer; the seasonal maximum occurring from May to July for ACTH and cortisol and in August for β-endorphin. At the peak of the cycle the ratio of β-endorphin to N-acetyl-β-endorphin was 22:1. The regulation of the seasonal cycle was investigated in a series of five experiments involving treatments with arginine vasopressin (AVP), corticotrophin-releasing factor (CRF) and the synthetic glucocorticoid, dexamethasone. Injection of AVP i.v. induced a dose-dependent increase in the plasma concentration of β-endorphin (AVP doses of 0, 0·07, 0·33 and 1·67 μg/kg). AVP (0·33 μg/kg) and CRF (1·67 μg/kg) given alone or in combination (equimolar doses), induced an increase in the plasma concentrations of β-endorphin and ACTH in spring, summer, autumn and winter, and produced a synergistic response when given together. The responses varied with season and were greatest in summer and autumn at the time of the seasonal increase in endogenous secretion. Dexamethasone injected i.v. at 68·04 μg/kg produced a decrease in the plasma concentrations of β-endorphin and ACTH, and the responses were also greatest in summer and autumn. A similar treatment with dexamethasone blocked the AVP-induced increase in the plasma levels of β-endorphin, indicating an action of dexamethasone on the pituitary gland. Administration of ACTH (0·33 μg/kg; i.v.) to rams pretreated with dexamethasone stimulated an increase in the plasma concentration of cortisol; this response varied with season, being greatest in spring at the time of the peak in the seasonal cycle in cortisol secretion. The administration of β-endorphin (0·33 pg/kg) failed to induce an increase in the plasma levels of cortisol at any season. Analysis of the hormone profiles in the control rams based on blood samples collected every 10 min for 8 h revealed pulsatile variations in the plasma concentration of ACTH; some of the spontaneous ACTH peaks were correlated with β-endorphin peaks. From these results in the Soay ram, we conclude that β-endorphin and ACTH are co-secreted from the pituitary gland following stimulation by AVP and CRF, and that adrenal glucocorticoids stimulated by ACTH can act in a negative feedback role at the level of the pituitary gland to inhibit the release of both β-endorphin and ACTH. These acute studies indicate a parallel control of β-endorphin and ACTH at all stages of the seasonal cycle, and a seasonal change in the secretion of AVP and CRF from the hypothalamus may constitute the 'drive' to the seasonal cycle in both β-endorphin and ACTH. There was, however, a notable difference in the timing of the seasonal cycle in β-endorphin compared with that of ACTH, which indicates some form of differential control of these two pituitary hormones. Journal of Endocrinology (1990) 124, 443–454

Pharmacokinetics and Response to Treatment Using a Combination of Fludarabine and Alemtuzumab (FluCam) in Patients with Relapsed/Refractory CLL.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4991-4991
Author(s):  
T. Elter ◽  
J. Kilp ◽  
T. Piironen ◽  
P. Borchmann ◽  
H. Schulz ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Plasma Levels ◽  
Residual Disease ◽  
Single Agent ◽  
Plasma Concentrations ◽  
Response Rates ◽  
Response To Treatment ◽  
Synergistic Activity ◽  
Refractory Disease

Abstract Combination chemoimmunotherapy regimens have shown substantial efficacy in the treatment of lymphoproliferative disorders, particularly in comparison to the efficacy of single-agent therapies. Fludarabine has become an established treatment regimen in CLL, and although overall response rates (ORR) in previously untreated patients range between 60% to 80%, patients who are refractory to fludarabine have poor outcomes. Alemtuzumab, the anti-CD52 monoclonal antibody, is the most effective single-agent therapy in CLL, and is capable of inducing minimal residual disease (MRD)-negative responses even among patients with fludarabine-refractory disease. Our previous clinical experience with the combination of alemtuzumab and fludarabine (FluCam) resulted in 83% ORR in 36 patients with relapsed/refractory CLL, with 30% achieving a complete response (CR; Elter et al J Clin Oncol2005;23:7024–7031). In addition, among 12 patients with fludarabine-refractory disease, 8 achieved responses (4 CRs), and median time-to-progression (TTP) for all patients was 13 months. In order to optimize the dose and schedule of the FluCam combination, we performed pharmacokinetic (PK) analysis of the previously reported 6-cycle regimen. PK data were collected for a 14-patient cohort that participated in the phase 2 FluCam trial. Median patient age was 60 years (range, 49–73), 9 patients had Binet C disease (5 were Binet B), and patients received a mean 2.5 prior therapies. Alemtuzumab 30 mg (after initial dose escalation) and fludarabine 30 mg/m2 were administered on days 1–3 of a 28-day cycle for up to 6 cycles. PK parameters were measured from samples collected before each subsequent cycle, and at days 1, 4, 7, 14, 21, 28, and 42, for a total of 158 patient samples, of which 120 were tested. Plasma concentration of alemtuzumab increased steadily from day 1 to day 4 of therapy to a median Cmax 1.55 mg/mL, but decreased to a median 0.145 mg/mL by 7 days after initiation of treatment. By day 21 of therapy, alemtuzumab plasma concentration decreased to undetectable levels. Because efficacy of alemtuzumab has been shown to correlate with serum levels of this antibody, significant improvement in progression free survival (PFS) may require a elevated plasma levels of alemtuzumab for the duration of the treatment cycle. Therefore, the significant responses seen in this trial can be attributed to documented synergistic activity between alemtuzumab and fludarabine, which has been demonstrated both in vitro and in vivo. Despite low CD4 counts through the duration of therapy, favorable safety results seen in the trial could be attributed to opportunity for hematologic recovery between treatment cycles. Detailed PK analysis is currently being completed and will be presented at the conference. Conclusions: Treatment with the FluCam immunotherapy combination yielded positive results among patients with fludarabine resistant/refractory CLL, a difficult-to-treat population. As shown previously, response rates correlate with higher alemtuzumab plasma concentrations. Therefore, longer PFS durations may require longer, more sustained alemtuzumab plasma levels, which may be achieved with either consolidation or maintenance.

Effect of pinealectomy on the plasma concentrations of prolactin, cortisol and testosterone in sheep in short and skeleton long photoperiods

1984 ◽  
Vol 100 (3) ◽  
pp. 287-294 ◽  
Author(s):  
B. R. Brinklow ◽  
J. M. Forbes
Keyword(s):  
Plasma Levels ◽  
Plasma Cortisol ◽  
Plasma Concentrations ◽  
Plasma Prolactin ◽  
Long Photoperiod

ABSTRACT Two experiments were carried out to investigate the effects of pinealectomy on the responses of prolactin, cortisol and testosterone to skeleton long photoperiods (7 h light: 10 h darkness: 1 h light: 6 h darkness; 7L: 10D: 1L: 6D) compared with short photoperiods (8L: 16D) in lambs. The first experiment included 23 female Suffolk cross sheep aged 10 months, of which six were pinealectomized. The skeleton long photoperiod significantly increased plasma levels of prolactin but this was blocked by pinealectomy; there was a peak around dusk and a trough around dawn and at the time of the 1-h period of light. There was no effect of either photoperiod or pinealectomy on plasma levels of cortisol. Testosterone was not measured in this experiment. In the second experiment there were 12 intact males and 11 castrated males aged 3 months; six of the lambs in each group were pinealectomized. Prolactin was again greatly stimulated by skeleton long photoperiods and the effect was blocked by pinealectomy; there was a trough in plasma prolactin at dawn in all groups. In addition, castration increased prolactin levels on two of the four sampling days. Plasma cortisol concentrations were significantly lower under skeleton long photoperiods and this was also blocked by pinealectomy; there was no effect of castration. Testosterone was much higher in intact males. After 10 weeks of exposure, skeleton long photoperiods produced significantly lower concentrations than short photoperiods in the intact ram with pineal glands but not in those which were pinealectomized. J. Endocr. (1984) 100, 287–294

Influence of opioid peptides on release from vasopressin and oxytocin neurones of the hypothalamoneurohypophyseal system: effects of naloxone in the conscious rat

1990 ◽  
Vol 68 (5) ◽  
pp. 568-574 ◽  
Author(s):  
Savio W. T. Cheng ◽  
Edward F. O'Connor ◽  
William G. North
Keyword(s):  
Plasma Concentration ◽  
Opioid Peptides ◽  
Plasma Concentrations ◽  
Plasma Osmolality ◽  
Plasma Sodium ◽  
Endogenous Opioid ◽  
Salt Loading ◽  
Conscious Rats ◽  
Basal Plasma ◽  
Acute And Chronic Treatments

We examined the effects of acute and chronic treatments with naloxone on release of vasopressin and oxytocin from the hypothalamoneurohypophyseal system (HNS) in conscious, chronically instrumented Long–Evans rats. Plasma concentrations of vasopressin-associated neurophysin and oxytocin-associated neurophysin were evaluated before and during an intravenous infusion of 18% saline at 100 μL∙kg−1 body weight∙min−1 for 60 min. Acute treatment with naloxone (2.75 μmol/kg, intravenous) did not measurably alter basal plasma osmolality or vasopressin-associated neurophysin concentration, but it caused a three-fold rise in basal plasma oxytocin-associated neurophysin concentration (16 ± 2 to 46 ± 3 fmol/mL, p < 0.005). Chronic treatment with naloxone (13.75 μmol/day, subcutaneous pellets) increased plasma osmolality (292 ± 1 to 300 ± 2 mosmol/kg H2O, p < 0.01) by day 5, but it had no measurable effects on basal vasopressin- or oxytocin-associated neurophysin concentration. There were also no significant differences in plasma sodium concentration (144.8 ± 1.1 vs. 142.2 ± 1.4 mequiv./L) under both conditions. Acute and chronic treatments with naloxone accompanied by salt loading produced a five- and four-fold decrease in the rates that plasma concentration of vasopressin-associated neurophysin changed with plasma osmolality, compared with untreated salt-loaded control rats. For oxytocin secretion from the HNS, both treatments accompanied by salt loading substantially decreased the threshold for changes in relation to plasma osmolality; the rise in plasma concentration of oxytocin-associated neurophysin was similar at all levels of hyperosmotic stimulation. A strongly correlated relationship between plasma oxytocin-associated neurophysin and plasma osmolality (r = 0.739) found for control animals became poorly correlated following treatments (acute, r = 0.173; chronic, r = −0.079). Our results suggest that in conscious rats, endogenous opioid peptides enhance the secretion of vasopressin from neurones of the HNS in response to hyperosmotic stimulation but inhibit both basal and stimulated release of oxytocin.Key words: naloxone, vasopressin, oxytocin, neurophysin, conscious rats.

Intranasal Cocaine: Dose Relationships of Psychological Effects and Plasma Levels

1983 ◽  
Vol 12 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Craig Van Dyke ◽  
James Ungerer ◽  
Peter Jatlow ◽  
Paul Barash ◽  
Robert Byck
Keyword(s):  
Plasma Concentration ◽  
Plasma Levels ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Psychological Effects ◽  
Acute Tolerance ◽  
Lidocaine Hydrochloride ◽  
Intranasal Cocaine ◽  
Cocaine Hydrochloride ◽  
Repeated Doses

We compared the psychological effects of three doses of intranasal cocaine hydrochloride (.2, .75, and 1.5 mg/kg) with cocaine plasma concentrations in four volunteers. Intranasal lidocaine hydrochloride (.2 mg/kg) was used as a topically active placebo. Peak “high” ratings were related to both dose and peak plasma concentrations. At a given plasma concentration, “high” ratings were greater when plasma levels were increasing than when they were decreasing. This indicates that acute tolerance by tachyphylaxis occurred after single doses. The cocaine “high” was a pleasant feeling but was without distinctive sensations. The dramatic effects of intranasal cocaine on the street may be related to larger or repeated doses as well as the setting.

Plasma Levels of Prolactin and Gonadotropins during the Reproductive Cycle of White-Crowned Sparrows (Zonotrichia leucophrys)

The Auk ◽  
1987 ◽  
Vol 104 (2) ◽  
pp. 208-217 ◽  
Author(s):  
Eve S. Hiatt ◽  
Arthur R. Goldsmith ◽  
Donald S. Farner
Keyword(s):  
Plasma Levels ◽  
Time Course ◽  
Plasma Concentrations ◽  
Gonadal Development ◽  
Prolactin Secretion ◽  
Temporal Association ◽  
Plasma Prolactin ◽  
Free Living ◽  
Zonotrichia Leucophrys ◽  
Testicular Weight

Abstract Plasma concentrations of prolactin, LH, and FSH were measured in free-living pairs of Zonotrichia leucophrys pugetensis throughout the natural breeding season, and during a photoperiodically induced cycle of gonadal development and regression in both sexes of captive Z. l. gambelii under controlled conditions. In free-living male Z. l. pugetensis plasma levels of FSH, which correlate well with changes in testicular weight reported previously, are higher than in females. Although only females of this species incubate, maximal levels of prolactin are observed in both sexes during late incubation. This is consistent with observations in other avian species and suggestive of a role for prolactin in incubation and associated parental behavior. The temporal association of elevated FSH with high levels of prolactin in females may represent a mechanism for maturation of ovarian follicles for the next clutch in this race, which typically raises as many as 3 broods per season. In the laboratory study on Z. l. gambelii, prolactin secretion in both sexes appears to have been induced photoperiodically in the absence of other environmental stimuli associated with incubation. The time course and magnitude of plasma prolactin levels were similar in both sexes, although levels were considerably lower than values obtained from incubating birds during the field study. Plasma levels of LH and FSH in females increased rapidly in response to photostimulation and began to decline after one week, whereas in males the pattern of increase and decrease of both gonadotropins was more gradual.

Epileptiform seizures in domestic fowl. VII. Plasma phenytoin concentrations and anticonvulsant activity

1978 ◽  
Vol 56 (2) ◽  
pp. 310-315 ◽  
Author(s):  
H. L. Davis ◽  
D. D. Johnson ◽  
R. D. Crawford
Keyword(s):  
Plasma Concentration ◽  
Plasma Levels ◽  
Domestic Fowl ◽  
Anticonvulsant Activity ◽  
Plasma Concentrations ◽  
Anticonvulsant Effect ◽  
Complete Protection ◽  
Intermittent Photic Stimulation ◽  
The Relationship ◽  
Epileptiform Seizures

Acute dose–response studies with phenytoin were conducted to determine the relationship between plasma levels and anticonvulsant effect in epileptic chickens. Phenytoin produced statistically significant reductions in both the incidence and severity of seizures in photosensitive epileptic chickens when the plasma concentrations exceeded 8.15 ± 0.89 μg/ml. A high correlation exists between plasma phenytoin concentrations and both the reduction in incidence or severity of seizures. However, the appearance of plasma concentration dependent neurological toxicities resulted in a failure to achieve complete protection against intermittent photic stimulation induced seizures.

The Effect of Halofenate or Halofenate Free Acid on Human, Rat and Guinea Pig Platelet Aggregation

1976 ◽  
Vol 35 (02) ◽  
pp. 358-363 ◽  
Author(s):  
D.H Minsker ◽  
P.T Jordan ◽  
P Kling ◽  
A MacMillan ◽  
H.B Hucker ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Plasma Concentration ◽  
Guinea Pig ◽  
Plasma Levels ◽  
Human Platelet ◽  
Free Acid ◽  
Secondary Phase ◽  
Inhibitory Effects ◽  
Human Platelet Aggregation ◽  
Induced Aggregation

SummaryHalofenate free acid (HFA), the major metabolite of the hypolipemic agent halofenate, blocked the secondary phase of human platelet aggregation induced by ADP, epinephrine, or thrombin; higher concentrations of clohbrate free acid (CFA) were required to produce similar inhibitory effects on platelet aggregation. HFA and CFA inhibited collagen-induced aggregation of human, rat, or guinea pig platelets. Halofenate orally administered to rats caused inhibition of collagen-induced aggregation when plasma levels of HFA exceeded 300 μg/ml, a clinically achievable human plasma concentration. The platelet inhibitory effects of clofibrate administration were less than those observed with halofenate administration.

Met-enkephalin stimulates secretion of ACTH in sheep

1986 ◽  
Vol 111 (3) ◽  
pp. 463-467 ◽  
Author(s):  
X.-M. Wang ◽  
J. P. Coghlan ◽  
M. Congiu ◽  
B. A. Scoggins ◽  
E. M. Wintour
Keyword(s):  
Opioid Peptides ◽  
Plasma Concentrations ◽  
Combined Effect ◽  
Corticotrophin Releasing Factor ◽  
Conscious Sheep ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Acth Release

ABSTRACT The ability of opioid peptides to affect plasma immunoreactive ACTH concentrations was examined in conscious sheep. Plasma concentrations of ACTH were significantly increased by an i.v. infusion of Met-enkephalin and its analogue (FK-33824). There was a dose-dependent increase in plasma concentrations of ACTH with a graded administration of FK-33824. The combined effect of Met-enkephalin and ovine corticotrophin-releasing factor (oCRF) or FK-33824 and oCRF on plasma concentrations of ACTH was greater than the effect of each peptide when given individually. This study demonstrates that Met-enkephalin and its analogue stimulate ACTH release in sheep. J. Endocr. (1986) 111, 463–467

Plasma concentrations of prolactin during egg laying and incubation in the ruffed grouse (Bonasa umbellus)

1979 ◽  
Vol 57 (8) ◽  
pp. 1624-1627 ◽  
Author(s):  
R. J. Etches ◽  
A. Garbutt ◽  
A. L. Middleton
Keyword(s):  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Egg Laying ◽  
Plasma Prolactin ◽  
Ruffed Grouse ◽  
Bonasa Umbellus ◽  
High Concentration ◽  
Double Antibody ◽  
High Concentrations

The plasma concentration of prolactin was measured following experimental photostimulation, during oviposition and during incubation in plasma from ruffed grouse by heterologous double-antibody radioimmunoassay. A slight increase in plasma prolactin was noted after photo-stimulation and a much larger increase was observed as subsequent eggs were laid. When the last egg was laid, plasma prolactin was maximal. This high concentration was maintained throughout incubation and declined to basal values when incubation was terminated by removal of the eggs. In hens that failed to incubate, plasma prolactin declined after the last oviposition.Brood patch development began before the first egg was laid but was not completed until incubation was initiated. Therefore, the patch began to develop when plasma concentrations of prolactin were slightly elevated but it was not fully formed until high concentrations of prolactin were maintained for several days.

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