Declining Plasma Progesterone Levels Eliminate Endogenous Opioid Peptide Suppression of LH Pulse Frequency on Day 22 of Gestation in the Rat

1988 ◽  
Vol 48 (6) ◽  
pp. 584-590 ◽  
Author(s):  
Elisa Devorshak-Harvey ◽  
Antonella Bona-Gallo ◽  
Robert V. Gallo
1989 ◽  
Vol 122 (2) ◽  
pp. 509-517 ◽  
Author(s):  
R. J. E. Horton ◽  
H. Francis ◽  
I. J. Clarke

ABSTRACT The natural opioid ligand, β-endorphin, and the opioid antagonist, naloxone, were administered intracerebroventricularly (i.c.v.) to evaluate effects on LH secretion in ovariectomized ewes and in ovariectomized ewes treated with oestradiol-17β plus progesterone either during the breeding season or the anoestrous season. Ovary-intact ewes were also studied during the follicular phase of the oestrous cycle. Jugular blood samples were taken at 10-min intervals for 8 h and either saline (20–50 μl), 100 μg naloxone or 10 μg β-endorphin were injected i.c.v. after 4 h. In addition, luteal phase ewes were injected i.c.v. with 25 μg β-endorphin(1–27), a purported endogenous opioid antagonist. In ovariectomized ewes, irrespective of season, saline and naloxone did not affect LH secretion, but β-endorphin decreased the plasma LH concentrations, by reducing LH pulse frequency. The effect of β-endorphin was blocked by administering naloxone 30 min beforehand. Treating ovariectomized ewes with oestradiol-17β plus progesterone during the breeding season reduced plasma LH concentrations from 6–8 μg/l to less than 1 μg/l. In these ewes, saline did not alter LH secretion, but naloxone increased LH pulse frequency and the plasma concentrations of LH within 15–20 min. During anoestrus, the combination of oestradiol-17β plus progesterone to ovariectomized ewes reduced the plasma LH concentrations from 3–5 μg/l to undetectable levels, and neither saline nor naloxone affected LH secretion. During the follicular phase of the oestrous cycle, naloxone enhanced LH pulse frequency, which resulted in increased plasma LH concentrations; saline had no effect. In these sheep, β-endorphin decreased LH pulse frequency and the mean concentrations of LH, and this effect was prevented by the previous administration of naloxone. The i.c.v. administration of β-endorphin(1–27) to luteal phase ewes did not affect LH secretion. These data demonstrate the ability of a naturally occurring opioid peptide to inhibit LH secretion in ewes during the breeding and non-breeding seasons, irrespective of the gonadal steroid background. In contrast, whilst the gonadal steroids suppress LH secretion in ovariectomized ewes during both seasons, they only appear to activate endogenous opioid peptide (EOP)-mediated inhibition of LH secretion during the breeding season. Furthermore, these data support the notion that LH secretion in ovariectomized ewes is not normally under the control of EOP, so that naloxone has no effect. Journal of Endocrinology (1989) 122, 509–517


1991 ◽  
Vol 3 (6) ◽  
pp. 709 ◽  
Author(s):  
AS Nanda ◽  
WR Ward ◽  
H Dobson

To create a clearly defined and uniform feedback phase of oestradiol, 1 mg oestradiol benzoate (OE2) was injected i.m. either 15-43 days post partum in 7 cows (Expt 1), or 12 h after prostaglandin oestrus synchronization of 4 cyclic cows (Expt 2 and 3). An endogenous opioid peptide (EOP) antagonist (250 mg naloxone), an EOP agonist (300 mg morphine), or a combination of the two was given in Expt 1, 2 and 3 respectively as a single i.v. injection in cows 16-18 h after OE2, i.e. in the negative feedback phase and before the expected onset of an induced luteinizing hormone (LH) surge. Blood samples were collected every 15 min for 1 h before and 2 h after each treatment. In Expt 1, naloxone failed to increase LH release when given during the negative feedback phase, but caused excessive release in one cow in which the LH surge had just begun. In all cows in Expt 2, morphine suppressed LH release (P less than 0.05). In Expt 3, naloxone prevented the suppressive effects of morphine for the first hour after treatment; a transient rise in LH occurred in one cow in which treatment was given 1 h before the start of the LH surge. In Expt 4, 250 mg naloxone was injected i.v. into 4 cows that had a plasma progesterone concentration of 1.5-3.1 ng mL-1 in the luteal phase of the oestrous cycle: naloxone failed to increase LH concentrations. It is concluded that LH can be further suppressed by opiates given to cows during the negative feedback phase of oestradiol.(ABSTRACT TRUNCATED AT 250 WORDS)


1987 ◽  
Vol 115 (2) ◽  
pp. 333-339 ◽  
Author(s):  
S. C. Stansfield ◽  
P. G. Knight ◽  
N. Z. Al-Mauly ◽  
M. J. Bryant

ABSTRACT Prepubertal ewes can, under certain circumstances, be stimulated to ovulate by the novel introduction of a ram. The endocrine response to the presence of the ram is characterized by a rapid increase in the frequency of episodic release of LH. The purpose of this study was to investigate the effect of the presence of a ram on LH pulse frequency in vivo, gonadotrophin-releasing hormone (GnRH) and β-endorphin concentrations in the median eminence, and on the influence of the endogenous opioid peptide agonist [d-Ala2,N-Phe4,Met(0)ol5]-enkephalin (FK 33–824) on basal and depolarization-induced release of GnRH from median eminence tissue superfused in vitro. The study was performed at two prepubertal ages in August and September. In September, the introduction of a ram resulted in an increase in pulsatile release of LH, which was associated with an increase in the rate of basal release of GnRH from median eminence tissue superfused in vitro, and the development of a marked ability of FK 33–824 to suppress depolarization-induced release of GnRH. The concentration of β-endorphin in the median eminence was reduced in animals exposed to the ram at this time. In contrast, the introduction of a ram in August failed to stimulate an increase in LH pulse frequency, basal release of GnRH in vitro was not altered and FK 33–824 was ineffective in reducing depolarization-induced release of GnRH. These results suggest that the premature onset of reproductive activity induced by exposure to the ram may involve the participation of the endogenous opioid peptide system. J. Endocr. (1987) 115, 333–339


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 927
Author(s):  
KK DurgaRao Viswanadham ◽  
Roland Böttger ◽  
Lukas Hohenwarter ◽  
Anne Nguyen ◽  
Elham Rouhollahi ◽  
...  

Opioids account for 69,000 overdose deaths per annum worldwide and cause serious side effects. Safer analgesics are urgently needed. The endogenous opioid peptide Leu-Enkephalin (Leu-ENK) is ineffective when introduced peripherally due to poor stability and limited membrane permeability. We developed a focused library of Leu-ENK analogs containing small hydrophobic modifications. N-pivaloyl analog KK-103 showed the highest binding affinity to the delta opioid receptor (68% relative to Leu-ENK) and an extended plasma half-life of 37 h. In the murine hot-plate model, subcutaneous KK-103 showed 10-fold improved anticonception (142%MPE·h) compared to Leu-ENK (14%MPE·h). In the formalin model, KK-103 reduced the licking and biting time to ~50% relative to the vehicle group. KK-103 was shown to act through the opioid receptors in the central nervous system. In contrast to morphine, KK-103 was longer-lasting and did not induce breathing depression, physical dependence, and tolerance, showing potential as a safe and effective analgesic.


1984 ◽  
Vol 123 (1) ◽  
pp. 148-155 ◽  
Author(s):  
Mitsuaki Suda ◽  
Kazuwa Nakao ◽  
Makoto Sakamoto ◽  
Takaaki Yoshimasa ◽  
Narito Morii ◽  
...  

2019 ◽  
Vol 33 (5) ◽  
pp. 577-588 ◽  
Author(s):  
Fabrício Calvo ◽  
Rafael Carvalho Almada ◽  
Tayllon dos Anjos-Garcia ◽  
Luiz Luciano Falconi- Sobrinho ◽  
Tatiana Paschoalin-Maurin ◽  
...  

Background: The endogenous opioid peptide system has been implicated in the neural modulation of fear and anxiety organised by the dorsal midbrain. Furthermore, previous results indicate a fundamental role played by inferior colliculus (IC) opioid mechanisms during the expression of defensive behaviours, but the involvement of the IC µ1-opioid receptor in the modulation of anxiety- and panic attack-related behaviours remains unclear. Using a prey-versus-snake confrontation paradigm, we sought to investigate the effects of µ1-opioid receptor blockade in the IC on the defensive behaviour displayed by rats in a dangerous situation. Methods: Specific pathogen-free Wistar rats were treated with microinjection of the selective µ1-opioid receptor antagonist naloxonazine into the IC at different concentrations (1.0, 3.0 and 5.0 µg/0.2 µL) and then confronted with rattlesnakes ( Crotalus durissus terrificus). The defensive behavioural repertoire, such as defensive attention, flat back approach (FBA), startle, defensive immobility, escape or active avoidance, displayed by rats either during the confrontations with wild snakes or during re-exposure to the experimental context without the predator was analysed. Results: The blockade of µ1-opioid receptors in the IC decreased the expression of both anxiety-related behaviours (defensive attention, FBA) and panic attack-related responses (startle, defensive immobility and escape) during the confrontation with rattlesnakes. A significant decrease in defensive attention was also recorded during re-exposure of the prey to the experimental apparatus context without the predator. Conclusion: Taken together, these results suggest that a decrease in µ1-opioid receptor signalling activity within the IC modulates anxiety- and panic attack-related behaviours in dangerous environments.


1988 ◽  
Vol 116 (3) ◽  
pp. 403-411 ◽  
Author(s):  
S. C. Stansfield ◽  
P. G. Knight ◽  
C. M. Howles ◽  
F. J. Cunningham

ABSTRACT Evidence from several species suggests that the endogenous opioid peptides participate in the regulation of gonadotrophin and prolactin secretion. The aim of the present study involving intact and ovariectomized prepubertal ewe lambs was to compare the effects in vivo of an opioid peptide agonist d-Ala2,N-Phe4,Met(0)ol5]-enkephalin (FK 33–824) and antagonist, naloxone, on concentrations of LH and prolactin in plasma, and levels of neurotransmitter metabolites in cerebrospinal fluid (CSF), with their effects in vitro on the release of gonadotrophin-releasing hormone (GnRH) and neurotransmitters from isolated median eminences. Infusion of FK 33–824 (0·5 mg/30 min) in vivo depressed plasma LH levels in both intact and ovariectomized lambs; this effect could be reversed by naloxone. In ovariectomized lambs, the inhibitory action of FK 33–824 on plasma LH levels was associated with a 13% rise in the concentration of the metabolite of 5-hydroxytryptamine, 5-hydroxyindolacetic acid (5-HIAA). Concurrent administration of naloxone resulted in an abrupt 33% fall in CSF levels of 5-HIAA. No significant changes in plasma concentrations of prolactin or CSF concentrations of the metabolites of dopamine were observed in response to the administration of FK 33–824 or FK 33–824 plus naloxone. That FK 33–824 inhibited LH release through a central mechanism was confirmed using superfused median eminences in vitro. Thus FK 33–824 (1 μmol/l) greatly diminished the release of GnRH induced by the introduction of a depolarizing stimulus (36 mmol K+/l) in tissue obtained from both intact and ovariectomized ewe lambs. Since neurotransmitter levels in superfusate samples were below the limit of detection of the high-performance liquid chromatography assay, it remains to be ascertained whether FK 33–824 concomitantly affected neurotransmitter release. These results lead us to conclude that FK 33–824 inhibits the secretion of LH, but not prolactin, in intact and ovariectomized prepubertal ewe lambs. The action of FK 33–824 is mediated, at the level of the median eminence, through a reduction of GnRH release. It is tentatively suggested that FK 33–824 may exert this inhibitory effect by stimulating the release of 5-hydroxytryptamine. J. Endocr. (1988) 116, 403–411


Neuropeptides ◽  
1996 ◽  
Vol 30 (4) ◽  
pp. 335-344 ◽  
Author(s):  
M.G Kolta ◽  
J.M Ngong ◽  
L.P Rutledge ◽  
K Pierzchala ◽  
G.R Van Loon

2013 ◽  
Vol 23 (15) ◽  
pp. 4347-4350 ◽  
Author(s):  
Julie E. Pickett ◽  
Kunihiko Nagakura ◽  
Anna R. Pasternak ◽  
Steven G. Grinnell ◽  
Susruta Majumdar ◽  
...  

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