Role of Endogenous Opioid Peptides in Mediating Progesterone-Induced Disruption of the Activation and Transmission Stages of the GnRH Surge Induction Process

Richter, Trevor; Spackman, D. S.; Robinson, Jane E.; Dye, S.; Harris, Thomas J.; Skinner, Donal C.; Evans, Neil P.

doi:10.1210/endo.142.12.8557

Cited by 11 publications

(8 citation statements)

References 54 publications

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“…10, top panel), after a delay corresponding to the duration of progesterone administration. A similar tendency of delayed surge onsets has been observed experimentally after progesterone treatments that were inefficient to block the surge (21). Because the experiments described in the literature have been conducted in induced (artificial) follicular phases, where the neurosecretory events are condensed compared to physiological follicular phases, the delays mentioned in our numerical experiments are greater than the corresponding ones in the biological experiments.…”

Section: Numerical Progesterone Blockadesupporting

confidence: 74%

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A Dynamical Model for the Control of the Gonadotrophin‐Releasing Hormone Neurosecretory System

Vidal

Clément

2010

J Neuroendocrinology

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The gonadotrophin-releasing hormone (GnRH) neurosecretory system involves both endocrine neurones and associated brain cells responsible for the control of GnRH release into the pituitary portal blood. Alternation between a pulsatile regime and the pre-ovulatory surge is the hallmark of GnRH secretion in ovarian cycles of female mammals. In previous studies, we have introduced a mathematical model of the pulse and surge GnRH generator and derived appropriate dynamics-based constraints on the model parameters, both to reproduce the right sequence of secretion events and to fulfil quantitative specifications on GnRH release. In the present study, we explain how these constraints amount to embedding time- and dose-dependent steroid control within the model. We further examine under which conditions the oestradiol-driven surge may be withdrawn by pre-surge progesterone administration and simulate both oestradiol and progesterone challenges in the pulsatile regime.

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Section: Numerical Progesterone Blockadesupporting

confidence: 74%

“…A series of studies (19)(20)(21)(22) have been dedicated to investigating experimental blockade of the oestradiol-induced GnRH surge by progesterone. It was first shown that progesterone acts centrally, on the hypothalamic level.…”

Section: Experimental Backgroundmentioning

confidence: 99%

A Dynamical Model for the Control of the Gonadotrophin‐Releasing Hormone Neurosecretory System

Vidal

Clément

2010

J Neuroendocrinology

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“…Endogenous opioid peptides are important regulators of the GnRH system, controlling both the preovulatory surge (17) and pulsatile secretion (18) of GnRH. OFQ has been shown to inhibit forskolin-induced GnRH secretion in a dose-dependent manner from rat hypothalamic fragments (19).…”

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confidence: 99%

Orphanin FQ: Evidence for a Role in the Control of the Reproductive Neuroendocrine System

et al. 2007

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Orphanin FQ (OFQ), also known as nociceptin, is a member of the endogenous opioid peptide family that has been functionally implicated in the control of pain, anxiety, circadian rhythms, and neuroendocrine function. In the reproductive system, endogenous opioid peptides are involved in the steroid feedback control of GnRH pulses and the induction of the GnRH surge. The distribution of OFQ in the preoptic area and hypothalamus overlaps with GnRH, and in vitro evidence suggests that OFQ can inhibit GnRH secretion from hypothalamic fragments. Using the sheep as a model, we examined the potential anatomical colocalization between OFQ and GnRH using dual-label immunocytochemistry. Confocal microscopy revealed that approximately 93% of GnRH neurons, evenly distributed across brain regions, were also immunoreactive for OFQ. In addition, almost all GnRH fibers and terminals in the external zone of the median eminence, the site of neurosecretory release of GnRH, also colocalized OFQ. This high degree of colocalization suggested that OFQ might be functionally important in controlling reproductive endocrine events. O RPHANIN FQ (OFQ), also known as nociceptin, is a member of the family of endogenous opioid peptides, which also includes ␤-endorphin, enkephalins, and dynorphin (1). Whereas sharing some homology with dynorphin, OFQ does not exhibit appreciable binding affinity for classical opioid receptors (1, 2); rather it functions as an endogenous ligand for the opioid receptor like (ORL)-1 receptor (1). OFQ cells are present in the preoptic area, anterior hypothalamus, and arcuate nucleus of the hypothalamus of the rat (3) and human (4). Functionally, OFQ has been implicated in a variety of systems including pain (5), anxiety (6), cardiovascular function (7), food intake (8), circadian rhythms (9), and cognition (10). There is also evidence that OFQ may play a role in neuroendocrine function: intracerebroventricular delivery of OFQ in the rat stimulates GH and prolactin (11, 12) and has been reported to both stimulate (13) and inhibit (14) corticosterone secretion. Sinchak et al. (15) have shown that OFQ delivered into the ventromedial nucleus facilitates lordosis in female rats in a dose-dependent manner. However, there has been relatively little attention to the possible role of OFQ in reproductive neuroendocrine function, specifically in the control of GnRH secretion.GnRH neurons, and their projections to the median eminence, control the secretion of pituitary LH and thus comprise the final common pathway for the neuroendocrine control of reproduction (16). Endogenous opioid peptides are important regulators of the GnRH system, controlling both the preovulatory surge (17) and pulsatile secretion (18) of GnRH. OFQ has been shown to inhibit forskolin-induced GnRH secretion in a dose-dependent manner from rat hypothalamic fragments (19). OFQ cells in the preoptic area and anterior hypothalamus overlap the site of a majority of GnRH perikarya (20 -22). In addition, OFQ fibers and ORL-1 receptors are present in high abund...

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“…This includes the regulation of hormone release in the hypothalamic-pituitary axis (Goodman et al, 1995;Richter et al, 2001;Pimpinelli et al, 2006;Brunton and Russell, 2008) and placenta (Belisle et al, 1988;Ahmed et al, 1989;Cemerikic et al, 1991), in pain modulation during pregnancy and labor (Dabo et al, 2010), and in the regulation of uterine motility (Zhu and Pintar, 1998). We characterised the effect of a met-enkephalin analog DAMEA on spontaneous human myometrial contractility.…”

Section: Discussionmentioning

confidence: 99%

Opioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-labouring myometrium

Fanning

McMorrow

Campion

et al. 2013

European Journal of Pharmacology

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TitleOpioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-laboring myometrium AbstractThe existence of opioid receptors in mammalian myometrial tissue is now widely accepted. Previously enkephalin degrading enzymes have been shown to be elevated in pregnant rat uterus and a met-enkephalin analogue has been shown to alter spontaneous contractility of rat myometrium. Here we have undertaken studies to determine the effects of met-enkephalin on in vitro human myometrial contractility and investigate the expression of opioid receptors in pregnant myometrium. Myometrial biopsies were taken from women undergoing elective caesarean delivery at term. Organ bath experiments were used to investigate the effect of the met-enkephalin analogue [D-Ala 2, D-met 5] enkephalin (DAMEA) on spontaneous contractility. A confocal immunofluorescent technique and real time PCR were used to determine the expression of protein and mRNA respectively for two opioid receptor subtypes, mu and delta. DAMEA had a concentration dependent inhibitory effect on contractile activity (1X10 -7 M to 1X10 -4 M; 54% reduction in contractile activity, P<0.001 at 1X10 -4 M concentration). Mu and delta opioid receptor protein sub-types and their respective mRNA were identified in all tissues sampled. This is the first report of opioid receptor expression and of an opioid mediated uterorelaxant action in term human non-laboring myometrium in vitro.

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Role of Endogenous Opioid Peptides in Mediating Progesterone-Induced Disruption of the Activation and Transmission Stages of the GnRH Surge Induction Process

Cited by 11 publications

References 54 publications

A Dynamical Model for the Control of the Gonadotrophin‐Releasing Hormone Neurosecretory System

A Dynamical Model for the Control of the Gonadotrophin‐Releasing Hormone Neurosecretory System

Orphanin FQ: Evidence for a Role in the Control of the Reproductive Neuroendocrine System

Opioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-labouring myometrium

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