Effects of placing micro-implants of melatonin in the mediobasal hypothalamus and preoptic area on the secretion of prolactin and β-endorphin in rams

1992 ◽  
Vol 134 (3) ◽  
pp. 437-448 ◽  
Author(s):  
G. A. Lincoln ◽  
K.-I. Maeda
Keyword(s):  
Body Weight ◽  
Preoptic Area ◽  
Plasma Concentrations ◽  
Prolactin Secretion ◽  
Early Summer ◽  
Mediobasal Hypothalamus ◽  
Continuous Administration ◽  
Blood Concentrations ◽  
Micro Implants ◽  
Short Days

ABSTRACT In a previous study, we showed that the local administration of melatonin into the mediobasal hypothalamus (MBH), but not the preoptic area (POA), caused a premature increase in the secretion of FSH and growth of the testes in sexually inactive Soay rams exposed to long days. To extend these observations, we have now measured blood concentrations of prolactin and β-endorphin and the associated peripheral responses in the same animals, to establish whether the treatments produced multiple endocrine changes such as those which occur following exposure to short days. Groups of rams were initially exposed to alternating 16 weekly periods of long days (16 h light: 8 h darkness; 16L:8D) and short days (8L:16D) for at least 9 months to entrain the seasonal cycles in the secretion of the pituitary hormones. The treatments were started at 10 weeks under long days, when the animals had a physiology characteristic of the early summer with high blood plasma concentrations of prolactin (associated with growth of the summer pelage), and low concentrations of β-endorphin (associated with low body weight). The animals were assigned at random to the following treatments: (i) micro-implants of melatonin in the MBH, (ii) microimplants of melatonin in the POA, (iii) empty implants in the MBH or POA to act as operated controls, and (iv) no surgery to act as unoperated controls (n=12 rams/treatment). The micro-implants consisted of 22-gauge stainless-steel needles with melatonin fused inside the tip. The implants were inserted bilaterally in the brain, and left in place for 12–14 weeks. The observations continued for a total of 28 weeks while the animals remained under long days. The administration of melatonin in the MBH induced a rapid decrease in plasma concentrations of prolactin while in the POA it induced a less marked but significant effect. The mean times to minimum concentrations of prolactin were 7·4±0·4, 17·3±2·8 and 26·0 ±0·3 weeks for the MBH, POA and combined control groups respectively (MBH vs control, P<0·001, POA vs control P<0·01. In the MBH group, the concentrations of prolactin subsequently increased to a maximum 6 weeks after the end of melatonin treatment. The changes in prolactin were accompanied by changes in growth and moulting of the pelage; only animals in the MBH group showed a conspicuous moult associated with the change from low to high prolactin secretion. There was also a marked effect of melatonin when given into the MBH, but not the POA, on plasma concentrations of β-endorphin, which was correlated with differences between groups in the cycle in body weight. In conclusion, continuous administration of melatonin into the MBH acts like a long-duration melatonin signal and induces a full sequence of biological responses normally evoked by transfer to short days. This is used as evidence that melatonin acts within or close to the MBH to induce the multiple effects of photoperiod in the ram. Journal of Endocrinology (1992) 134, 437–448

Reproductive effects of placing micro-implants of melatonin in the mediobasal hypothalamus and preoptic area in rams

1992 ◽  
Vol 132 (2) ◽  
pp. 201-215 ◽  
Author(s):  
G. A. Lincoln ◽  
K.-I. Maeda
Keyword(s):  
Reproductive Cycle ◽  
Preoptic Area ◽  
Plasma Concentrations ◽  
Mediobasal Hypothalamus ◽  
Reproductive Effects ◽  
Long Day ◽  
Reproductive Axis ◽  
Micro Implants ◽  
The Brain ◽  
Short Days

ABSTRACT The reproductive effects of placing micro-implants of melatonin in the mediobasal hypothalamus (MBH) and preoptic area (POA) were monitored in Soay rams. Groups of animals were initially conditioned to alternating 16 weekly periods of long days (16 h light:8 h darkness; 16L:8D) and short days (8L:16D) for at least 9 months to entrain the seasonal reproductive cycle. All experiments were then initiated at 10 weeks under long days when the animals were sexually inactive. In experiment 1, rams were exposed to short days for 14 weeks or maintained on long days to illustrate the photoperiodically induced re-activation and regression of the reproductive axis. In experiments 2–4, rams received micro-implants of melatonin in the MBH or POA, or received control treatments (sham-operated or no surgery) for 12–14 weeks while maintained on long days (total of 12 animals/treatment). The melatonin implants consisted of 22-gauge stainless-steel cannulae with melatonin fused inside the tip and were placed bilaterally in the brain. Incubation of the implants in Tricine-buffered saline (pH 8·0) at 37 °C showed that the release rate of melatonin was relatively constant after an initial peak in week 1 (means ± s.e.m.: 3·42 ± 0·43 μg/24 h). Rams with melatonin implants placed in the MBH, but not in the POA, showed a consistently earlier re-activation of the reproductive axis compared with the control animals in all three experiments (12/12 for MBH vs 2/12 for POA). The mean time to maximum testicular diameter was 12·2 ± 0·9, 21·6 ± 1·8 and 22·3 ± 1·2 weeks for the MBH, POA and combined control groups respectively (MBH vs control, P < 0·01; analysis of variance). The premature growth of the testes in the MBH group was associated with an earlier increase in the blood plasma concentrations of FSH and testosterone, and the appearance of the sexual skin coloration. Removal of the implants resulted in a decline in all reproductive parameters. The melatonin treatments did not cause a detectable increase in the peripheral concentrations of melatonin, or affect the diurnal rhythm in melatonin which reflected the long-day photoperiod. When implants containing 125I-labelled melatonin were introduced into the brain the associated radioactivity was localized to within 1 mm of the implants. The overall results demonstrate that the constant administration of melatonin into the MBH blocks the effect of the endogenous long-day melatonin signal and induces gonadal redevelopment. This provides the first evidence that melatonin acts within or close to the MBH to relay effects of photoperiod and influence the timing of the reproductive cycle in the ram. Journal of Endocrinology (1992) 132, 201–215

Regulation of the photoperiod-induced cycle in the peripheral blood concentrations of β-endorphin and prolactin in the ram: role of dopamine and endogenous opioids

1990 ◽  
Vol 127 (3) ◽  
pp. 461-469 ◽  
Author(s):  
E. Ssewannyana ◽  
G. A. Lincoln
Keyword(s):  
Plasma Concentrations ◽  
Prolactin Secretion ◽  
Endogenous Opioids ◽  
Fold Change ◽  
Opioid Antagonist ◽  
Light Cycle ◽  
Blood Concentrations ◽  
The Mean ◽  
Short Days

ABSTRACT In a group of adult Soay rams housed indoors under an artificial light cycle of alternating 16-week periods of long and short days, there was a conspicuous longterm cycle in the peripheral plasma concentrations of β-endorphin and prolactin. The levels of β-endorphin were highest under short days and lowest under long days (15-fold change), and inversely related to the changes in the plasma levels of prolactin (120-fold change). The role of dopamine in the control of β-endorphin and prolactin was investigated in a series of experiments, conducted under both long and short days, in which rams were treated with dopamine receptor agonists (dopamine and bromocriptine) and antagonists (pimozide and sulpiride). Naloxone (opioid antagonist) was also administered to assess the additional involvement of endogenous opioids. Dopamine injected i.v. (6·6 mg/kg every 10 min) did not significantly affect the mean plasma concentrations of β-endorphin and prolactin under either long or short days. Pimozide (0·08 mg/kg i.m. every 2 h) caused a large increase in the mean plasma concentrations of β-endorphin and prolactin under long days but not short days. Naloxone (1·6 mg/kg, i.v.), administered alone or in combination with dopamine or pimozide, had no effect on the mean plasma concentrations of β-endorphin and prolactin, except under short days when, combined with pimozide, it induced an increase in the plasma concentrations of the two polypeptides. Bromocriptine (0·06 mg/kg, s.c.) caused a significant decrease in the plasma concentrations of both β-endorphin and prolactin; this effect was most marked at the times of increased secretion (under short days for β-endorphin and under long days for prolactin). Sulpiride (0·59 mg/kg, s.c.) produced the converse effect and caused an increase in the plasma concentrations of β-endorphin and prolactin with the amplitude and duration of the effect varying with the stage of the photoperiod-induced cycle. From these results in the Soay ram, we conclude that dopamine inhibits β-endorphin and prolactin secretion by way of D2 receptors under both long and short days. Endogenous opioids interact with dopamine, augmenting this inhibition under short days. Differences in the acute responses in the secretion of β-endorphin and prolactin, and the inverse relationship between β-endorphin and prolactin during the cycle, indicate that different regulatory systems involving dopamine influence the two pituitary polypeptides. Journal of Endocrinology (1990) 127, 461–469

Pineal denervation by cervical sympathetic ganglionectomy suppresses the role of photoperiod on pregnancy or pseudopregnancy, body weight and moulting periods in the mink (Mustela vison)

1985 ◽  
Vol 107 (1) ◽  
pp. 31-39 ◽  
Author(s):  
L. Martinet ◽  
D. Allain ◽  
Y. Chabi
Keyword(s):  
Body Weight ◽  
Environmental Factors ◽  
Prolactin Secretion ◽  
Corpora Lutea ◽  
Progesterone Secretion ◽  
Cervical Ganglion ◽  
Cervical Sympathetic ◽  
Implantation Period ◽  
Short Days

ABSTRACT In mink, termination of the delayed implantation period, following reactivation of the corpora lutea, and onset of the spring moult are associated with a rise in prolactin secretion triggered by increasing daylength, while decreasing daylength induces the autumn moult. To establish whether suppression of the function of the pineal rendered the mink unresponsive to daylength changes, the superior cervical ganglion was removed bilaterally 2–4 weeks before mating. Intact and operated females were then left outdoors or were put under a lighting regime of either 15 h light: 9 h darkness (15L: 9D) or 8L: 16D. In July, at the end of the spring moult, the 15L: 9D lighting regime was changed to one of 8L: 16D. Under artificial photoperiods ganglionectomy suppressed the stimulatory role of long days and the inhibitory role of short days on prolactin secretion, and consequently on progesterone secretion and spring moult. Neither was the autumn moult, induced early in intact females by the change to a short photoperiod, advanced in ganglionectomized females, showing that the latter were unresponsive to the artificial modification of the photoperiod. However, in animals kept outdoors, prolactin and progesterone secretion and spring moult were not changed by ganglionectomy. Increase in body weight and autumn moult were only slightly delayed by the operation suggesting that other environmental factors had replaced the synchronizing effect of the daylength changes. Alternatively the desynchronization between intact females responsive to photoperiodism and those rendered unresponsive may be too slow to be observed soon after ganglionectomy. J. Endocr. (1985) 107, 31–39

Pharmacokinetics of Dopamine in Healthy Male Subjects

2000 ◽  
Vol 92 (2) ◽  
pp. 338-338 ◽  
Author(s):  
Drew A. MacGregor ◽  
Timothy E. Smith ◽  
Richard C. Prielipp ◽  
John F. Butterworth ◽  
Robert L. James ◽  
...  
Keyword(s):  
Body Weight ◽  
Washout Period ◽  
Pharmacokinetic Model ◽  
Plasma Concentrations ◽  
Healthy Male ◽  
Blood Concentrations ◽  
Homogeneous Population ◽  
Dopamine Infusion ◽  
Arterial Blood ◽  
Male Subjects

Background Dopamine is an agonist of alpha, beta, and dopaminergic receptors with varying hemodynamic effects depending on the dose of drug being administered. The purpose of this study was to measure plasma concentrations of dopamine in a homogeneous group of healthy male subjects to develop a pharmacokinetic model for the drug. Our hypothesis was that dopamine concentrations can be predicted from the infusion dose using a population-based pharmacokinetic model. Methods Nine healthy male volunteers aged 23 to 45 yr were studied in a clinical research facility within our academic medical center. After placement of venous and arterial catheters, dopamine was infused at 10 microg x kg(-1) x min(-1) for 10 min, followed by a 30-min washout period. Subsequently, dopamine was infused at 3 microg x kg(-1) x min(-1) for 90 min, followed by another 30-min washout period. Timed arterial blood samples were centrifuged, and the plasma was analyzed by high-performance liquid chromatography. Mixed-effects pharmacokinetic models using NONMEM software (NONMEM Project Group, University of California, San Francisco, CA) were used to determine the optimal compartmental pharmacokinetic model for dopamine. Results Plasma concentrations of dopamine varied from 12,300 to 201,500 ng/l after 10 min of dopamine infusion at 10 microg x kg(-1) x min(-1). Similarly, steady-state dopamine concentrations varied from 1,880 to 18,300 ng/l in these same subjects receiving 3-microg x kg(-1) x min(-1) infusions for 90 min. A two-compartment model adjusted for body weight was the best model based on the Schwartz-Bayesian criterion. Conclusions Despite a homogeneous population of healthy male subjects and weight-based dosing, there was 10- to 75-fold intersubject variability in plasma dopamine concentrations, making standard pharmacokinetic modeling of less utility than for other drugs. The data suggest marked intraindividual and interindividual variability in dopamine distribution and/or metabolism. Thus, plasma dopamine concentrations in patients receiving dopamine infusion at identical rates may vary profoundly. Our data suggest that dosing dopamine based on body weight does not yield predictable blood concentrations.

Hypothalamic control of photoperiod-induced cycles in food intake, body weight, and metabolic hormones in rams

2001 ◽  
Vol 281 (1) ◽  
pp. R76-R90 ◽  
Author(s):  
Gerald A. Lincoln ◽  
Stewart M. Rhind ◽  
Sueli Pompolo ◽  
Iain J. Clarke
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Sheep Model ◽  
Blood Concentrations ◽  
Metabolic Hormones ◽  
Melanocyte Stimulating Hormone ◽  
Induced Changes ◽  
And Control ◽  
Short Days

This study used a hypothalamo-pituitary disconnected (HPD) sheep model to investigate the central regulation of long-term cycles in voluntary food intake (VFI) and body weight (BW). VFI, BW, and circulating concentrations of metabolic hormones [α-melanocyte-stimulating hormone (α-MSH), insulin-like growth factor-1 (IGF-1), insulin, and leptin] were measured in HPD and control Soay rams exposed to alternating 16 weekly periods of long and short days for 80 wk. In the controls, the physiology was cyclical with a 32-wk periodicity corresponding to the lighting regimen. VFI and BW increased under long days to a maximum early into short days, and there were associated increases in blood concentrations of α-MSH, insulin, and leptin. In the HPD rams, there were no significant photoperiod-induced changes in any of the parameters. VFI increased after surgery for 8 wk and then gradually declined, although BW increased progressively and the HPD rams became obese. Concentrations of α-MSH, insulin, and leptin in peripheral blood were permanently increased (>200%), and levels of IGF-1 decreased (<55%). The HPD lesion effectively destroyed the entire median eminence [no nerve terminals immunostained for tyrosine hydroxylase (TH) and gonadotropin-releasing hormone] and the adjacent arcuate nucleus (no perikarya immunostained for proopiomelanocortin or TH, and no cells expressed neuropeptide Y mRNA). The results support the conclusion that arcuate hypothalamic systems generate long-term rhythms in VFI, BW, and energy balance.

scholarly journals Bioavailability and Sustained Plasma Concentrations of CoQ10 in Healthy Volunteers by a Novel Oral Timed-Release Preparation

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 527 ◽  
Author(s):  
Alessio Martucci ◽  
Delia Reurean-Pintilei ◽  
Anamaria Manole
Keyword(s):  
Single Dose ◽  
Coenzyme Q10 ◽  
Plasma Concentrations ◽  
Antioxidant Properties ◽  
Sharp Decrease ◽  
Continuous Administration ◽  
Blood Concentrations ◽  
Mean Values ◽  
High Concentrations ◽  
Group B

Coenzyme Q10 (CoQ10) is a natural compound with potent antioxidant properties. Its provision through diet does not always allow adequate levels in the human body, and supplementation is often necessary. This bioavailability study intended to explore the plasma concentration levels of a novel CoQ10 oral preparation (COQUN®, Coenzyme Q10 Miniactives Retard 100 mg capsules) mimicking assumption on a regular basis. Twenty-four healthy adults tested a single dose of CoQ10 100 mg in one day to assess bioavailability. After a one week wash-out period, they were randomly assigned (1:1) to continuous administration for four weeks: Group A (n = 12) 100 mg once a day (OD); and Group B (n = 12) 100 mg twice a day (BID). During the single dose phase, Cmax was observed at 4 h, and the mean values of AUCt and Tmax were 8754 μg/mL·h and 4.29 h, respectively. The multiple dose phase showed increasing plasma levels up to 7 days after the start of administration, and sustained high concentrations during the all administration period. No relevant adverse events were reported. These results show that Miniactives® technology can release CoQ10 to allow high constant blood concentrations without a sharp decrease. This may be the first step of evidence for a potential new antioxidative treatment in human chronic diseases deserving high CoQ10 levels.

scholarly journals Response of Pre-pubertally Castrated Rams and Ewes to Artificial PhotoperiodChanges in Plasma LH and Prolactin

1986 ◽  
Vol 39 (4) ◽  
pp. 417
Author(s):  
AL Poulton
Keyword(s):  
Plasma Concentrations ◽  
Prolactin Secretion ◽  
Light Regime ◽  
Constant Light ◽  
Ovarian Activity ◽  
Artificial Light ◽  
Short Days

Castrate rams and ovariectomized ewes were maintained in the presence of entire rams and ewes and subjected to successive periods of alternating 6 h light: 18 h darkness ('short' days) and 18 h light: 6 h darkness ('long' days) preceeded by a period of 12 h light: 12 h darkness ('constant' light days). Plasma concentrations of LH and prolactin were measured in the castrate animals in order to determine how LH and prolactin secretion responded to (i) the artificial light regime and (ii) corresponding periods of elevated or depressed testicular and ovarian activity in the entire rams and ewes.

INFLUENCE OF METYRAPONE ON PLASMA CONCENTRATIONS OF TESTOSTERONE AND ANDROSTENEDIONE IN MAN

1971 ◽  
Vol 68 (3) ◽  
pp. 576-584 ◽  
Author(s):  
K. O. Nilsson ◽  
B. Hökfelt
Keyword(s):  
Body Weight ◽  
Male Patient ◽  
Gradual Increase ◽  
Plasma Concentrations ◽  
Plasma Testosterone ◽  
Testosterone Levels ◽  
Basal Plasma ◽  
Normal Males ◽  
A Minor ◽  
Secondary Hypogonadism

ABSTRACT Metyrapone was administered either orally, 750 mg every four h, in a total of six doses, or intravenously 30 mg per kg body weight as a four h infusion. In three males with normal endocrine functions, metyrapone given orally or intravenously induced a fall in plasma testosterone and an elevation of androstenedione within 2–8 h. When metyrapone was administered to a patient given dexamethasone to suppress endogenous ACTH production, the androstenedione levels did not alter whereas the testosterone levels showed a slight, transient decrease. In two normal females metyrapone administration was followed by a marked increase in plasma androstenedione whereas testosterone showed only a minor, gradual increase. In one male patient with Addison's disease the basal plasma testosterone was normal whereas the level of androstenedione was low. Following metyrapone intravenously, there was a slight suppression of plasma testosterone but no change in the androstenedione concentration. In one patient with primary hypogonadism, two with secondary hypogonadism and two with Klinefelter's syndrome the plasma testosterone was low under basal conditions and did not change following metyrapone. Basal plasma androstenedione was within the range for normal males and increased markedly following metyrapone in all the cases.

Effects of ageing and exogenous melatonin on pituitary responsiveness to GnRH in rats

Reproduction ◽  
2000 ◽  
pp. 151-156 ◽  
Author(s):  
E Diaz ◽  
D Pazo ◽  
AI Esquifino ◽  
B Diaz
Keyword(s):  
Body Weight ◽  
Reproductive System ◽  
Plasma Concentrations ◽  
Pituitary Hormones ◽  
Female Rats ◽  
Control Groups ◽  
Melatonin Treatment ◽  
Exogenous Melatonin ◽  
Reproductive Axis ◽  
Effect Of Age

The effect of age and melatonin on the activity of the neuroendocrine reproductive system was studied in young cyclic (3-5 months-old), and old acyclic (23-25 month-old) female rats. Pituitary responsiveness to a bolus of GnRH (50 ng per 100 g body weight) was assessed at both reproductive stages in control and melatonin-treated (150 micrograms melatonin per 100 g body weight each day for 1 month) groups. After this experiment, female rats were treated for another month to study the influence of ageing and melatonin on the reproductive axis. Plasma LH, FSH, prolactin, oestradiol and progesterone were measured. A positive LH response to GnRH was observed in both control groups (cyclic and acyclic). However, a response of greater magnitude was observed in old acyclic rats. Melatonin treatment reduced this increased response in acyclic rats and produced a pituitary responsiveness similar to that of young cyclic rats. FSH secretion was independent of GnRH administration in all groups, indicating desynchronization between LH and FSH secretion in response to GnRH in young animals and during senescence. No effect on prolactin was observed. Significantly higher LH (3009.11 +/- 1275.08 pg ml(-1); P < 0.05) and FSH concentrations (5879.28 +/- 1631.68 pg ml(-1); P < 0.01) were seen in acyclic control rats. After melatonin treatment, LH (811.11 +/- 89.71 pg ml(-1)) and FSH concentrations (2070 +/- 301.62 pg ml(-1)) decreased to amounts similar to those observed in young cyclic rats. However, plasma concentrations of oestradiol and progesterone were not reduced. In conclusion, the results of the present study indicate that, during ageing, the effect of melatonin is exerted primarily at the hypothalamo-pituitary axis rather than on the ovary. Melatonin restored the basal concentrations of pituitary hormones and pituitary responsiveness to similar values to those observed in young rats.

scholarly journals Ileal transposition helps to regulate plasma hepatokine levels in obese Zucker (Crl:ZUC(ORL)-Leprfa) rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dominika Stygar ◽  
Tomasz Sawczyn ◽  
Agnieszka Dulska ◽  
Elżbieta Chełmecka ◽  
Łukasz Mielańczyk ◽  
...  
Keyword(s):  
Body Weight ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
The Body ◽  
Retinol Binding Protein ◽  
Fibroblast Growth Factor 21 ◽  
Adult Males ◽  
Total Lipids ◽  
Ileal Transposition ◽  
Sham Surgery

AbstractWe studied the long-term effect of ileal transposition (IT) metabolic surgery on the hepatokines: retinol-binding protein-4 (RBP4), α-2-HS-glycoprotein (aHSG/fetuin-A), and fibroblast growth factor 21 (FGF21), C-reactive protein (CRP) plasma levels, glucose metabolism, body weight, liver histology, as well as total lipids concentration in muscle, liver, and fat tissue of obese Zucker (Crl:ZUC(ORL)-Leprfa) rats. 14 adult males were randomly submitted either to IT or SHAM (control) surgery. Pre-operative hepatokines plasma levels were not significantly different in rats submitted to IT or SHAM protocol. Three months after the procedures the plasma levels of RBP4, aHSG, FGF21, and CRP were significantly lower in IT-operated animals when compared to SHAM-operated group. Three and 12 weeks after the IT and SHAM surgery, the AUCOGTT were significantly lower than AUCOGTT before the surgery. HOMA-IR was lower in rats after IT surgery in comparison to the SHAM-operated rats. Muscle and liver total lipids concentration was reduced after the IT procedure when compared to pre-IT conditions. IT had a significant reductive impact on the body weight in comparison to SHAM surgery in the 4th, 6th, 8th, and 10th week after the surgery. We conclude that IT reduces hepatokines’ plasma concentrations, muscle and liver total lipids concentration but not the inflammatory processes in the liver of Zucker (Crl:ZUC(ORL)-Leprfa) rats.

Sign in / Sign up

Export Citation Format

Share Document