Induction of LH hypersecretion in cyclic rats during the afternoon of oestrus by oestrogen in conjunction with progesterone antagonism or opioidergic blockade

1988 ◽  
Vol 117 (2) ◽  
pp. 229-235 ◽  
Author(s):  
R. H. Lustig ◽  
D. W. Pfaff ◽  
J. Fishman
Keyword(s):  
Opiate Antagonist ◽  
Endogenous Opioid ◽  
Lh Surge ◽  
Ru 486 ◽  
Low Concentrations ◽  
Exogenous Oestrogen ◽  
Long Acting ◽  
Lh Secretion

ABSTRACT The pro-oestrous secretion of progesterone that follows the LH surge in the rat limits the expression of the daily signal for LH surge initiation until the following oestrous cycle. This study explored the role of endogenous opioid peptides in the extinction by progesterone of the signal for the LH surge induced by oestrogen. Intact cyclic rats underwent external jugular venous cannulation on dioestrus, and were allowed to elicit a spontaneous pro-oestrous LH surge. On the afternoon of pro-oestrus, rats received an s.c. injection of oestradiol and an s.c. injection of either oil, 17β-hydroxy-11β-(4-dimethylaminophenyl)17α-(prop-1-ynyl)oestra-4,9,dien-3-one (RU 486; a synthetic anti-progestin), or N-cyclopropylmethyl-6-desoxy-6-methylene-noroxy-morphone (nalmefene; a long-acting opiate antagonist). Repeat doses of each were administered on the morning of oestrus to maintain increased oestrogen levels, and either progesterone or opioidergic blockade. Plasma was obtained from 13.00 to 19.00 h on oestrus for determination of the concentration of rat LH. Rats treated with oestradiol alone demonstrated consistently low concentrations of LH throughout the afternoon of oestrus. Rats treated with both oestradiol and either RU 486 or nalmefene demonstrated spontaneous augmentations of rat LH concentration during the afternoon of oestrus, which, although of diminished amplitude as compared with that seen in pro-oestrus, were consistent with a reactivation of the LH surge-generating mechanism. Rats treated with nalmefene in the absence of oestradiol were unable to augment LH secretion spontaneously. These experiments suggest that antagonism of progesterone action at the time of the LH surge prevents the extinction of the LH surge signal, so that it may be reactivated the next day by exogenous oestrogen. They similarly demonstrate that persistent opioidergic antagonism will permit oestrogen to reactivate the daily LH surge signal. The similar properties of an anti-progestin and an anti-opiate in this study suggest that the pro-oestrous progesterone rise extinguishes consecutive daily LH surges, in part, through increases in opioidergic tone. J. Endocr. (1988) 117, 229–235

Opioidergic modulation of the oestradiol-induced LH surge in the rat: roles of ovarian steroids

1988 ◽  
Vol 116 (1) ◽  
pp. 55-69 ◽  
Author(s):  
R. H. Lustig ◽  
D. W. Pfaff ◽  
J. Fishman
Keyword(s):  
Opiate Receptors ◽  
Ovariectomized Rats ◽  
Low Doses ◽  
Opiate Antagonist ◽  
Lh Surge ◽  
Biphasic Effect ◽  
The Status ◽  
Long Acting ◽  
Time Specific ◽  
Lh Secretion

ABSTRACT Sex steroids convey information on the status of the reproductive system, which the brain is able to integrate to promote ovulation, in the form of the LH surge. The present studies examined the influence of alterations in central opioidergic tone to initiate the LH surge, and the roles of oestradiol and progesterone to effect changes in opioidergic tone, by antagonizing this activity using either naloxone or nalmefene (N-cyclopropylmethyl-6-desoxy-6-methylene-noroxymorphone), a long-acting μ- and κ-opiate antagonist. The timing and amplitude of the LH surge was examined in (1) cyclic rats in pro-oestrus and (2) ovariectomized rats with varying doses of oestradiol supplementation. Plasma was obtained hourly through an indwelling intra-atrial catheter between 13.00 and 19.00 h, and later assayed for LH and oestradiol concentrations by radioimmunoassay. Rats treated with either nalmefene or progesterone on pro-oestrus demonstrated similar advances in the time of initiation of the LH surge by 1–2 h compared with control rats. The effects of nalmefene and progesterone were evident within 2 and 3–5 h of their administration respectively. Conversely, rats treated with progesterone on dioestrus demonstrated low prooestrous oestradiol levels and abolition of the prooestrous LH surge, but continuous naloxone infusion restored the pro-oestrous LH surge, with raised oestradiol concentrations. In ovariectomized rats without oestradiol supplentation, nalmefene alone was able to increase basal LH levels, but unable to facilitate a spontaneous rise in LH amplitude indicative of an LH surge. Supplementation with low doses of oestradiol was itself ineffective in facilitating a spontaneous rise in LH concentration, but nalmefene co-administration significantly potentiated the ability of low doses of oestradiol to induce augmented LH secretion, in addition to advancing the timing of the spontaneous LH rise. Similarly, progesterone co-administration to ovariectomized, oestradiol-primed rats significantly advanced and augmented LH hypersecretion. The results of these experiments are consistent with the concept that central opioidergic systems normally restrain the initiation of the LH surge, and that blocking opiate receptors removes this inhibition. They advance the hypothesis that oestradiol, the essential signal for LH surge induction, has, as one consequence of its action, the time-specific inhibition of hypothalamic opioidergic tone in the afternoon, which would otherwise restrain the LH surge-generating mechanism. Finally, the biphasic effect of progesterone on the LH surge appears to be mediated through dichotomous actions on opioidergic tone; in the highoestrogen state, progesterone advances LH surge timing, mimicking the effect of an opiate antagonist, but in the low-oestrogen state, progesterone abolishes the subsequent LH surge, and its effect is negated by an opiate antagonist. J. Endocr. (1988) 116, 55–69

Treatment of Antidepressant-Resistant Bulimia with Naltrexone

1987 ◽  
Vol 16 (4) ◽  
pp. 305-309 ◽  
Author(s):  
Jeffrey M. Jonas ◽  
Mark S. Gold
Keyword(s):  
Eating Disorders ◽  
Preliminary Data ◽  
Endogenous Opioids ◽  
Opiate Antagonist ◽  
Percent Reduction ◽  
Bulimic Symptoms ◽  
Long Acting ◽  
Insight Into

Ten individuals with antidepressant-resistant bulimia were treated with the long-acting opiate antagonist naltrexone. Seven of the ten experienced at least a 75 percent reduction of their bulimic symptoms, and have maintained their improvment on three to five month follow-up. These preliminary data suggest that naltrexone may be of use in bulimia unresponsive to standard antidepressant therapy, and may provide insight into the role of endogenous opioids in the etiology of eating disorders.

scholarly journals Release of Norepinephrine in the Preoptic Area Activates Anteroventral Periventricular Nucleus Neurons and Stimulates the Surge of Luteinizing Hormone

Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 363-374 ◽  
Author(s):  
Raphael E. Szawka ◽  
Maristela O. Poletini ◽  
Cristiane M. Leite ◽  
Marcelo P. Bernuci ◽  
Bruna Kalil ◽  
...  
Keyword(s):  
Positive Feedback ◽  
Preoptic Area ◽  
Lh Surge ◽  
Ovx Rats ◽  
Selective Lesion ◽  
Periventricular Nucleus ◽  
Reverse Microdialysis ◽  
Fos Expression ◽  
Lh Secretion

The role of norepinephrine (NE) in regulation of LH is still controversial. We investigated the role played by NE in the positive feedback of estradiol and progesterone. Ovarian-steroid control over NE release in the preoptic area (POA) was determined using microdialysis. Compared with ovariectomized (OVX) rats, estradiol-treated OVX (OVX+E) rats displayed lower release of NE in the morning but increased release coincident with the afternoon surge of LH. OVX rats treated with estradiol and progesterone (OVX+EP) exhibited markedly greater NE release than OVX+E rats, and amplification of the LH surge. The effect of NE on LH secretion was confirmed using reverse microdialysis. The LH surge and c-Fos expression in anteroventral periventricular nucleus neurons were significantly increased in OVX+E rats dialyzed with 100 nm NE in the POA. After Fluoro-Gold injection in the POA, c-Fos expression in Fluoro-Gold/tyrosine hydroxylase-immunoreactive neurons increased during the afternoon in the A2 of both OVX+E and OVX+EP rats, in the locus coeruleus (LC) of OVX+EP rats, but was unchanged in the A1. The selective lesion of LC terminals, by intracerebroventricular N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, reduced the surge of LH in OVX+EP but not in OVX+E rats. Thus, estradiol and progesterone activate A2 and LC neurons, respectively, and this is associated with the increased release of NE in the POA and the magnitude of the LH surge. NE stimulates LH secretion, at least in part, through activation of anteroventral periventricular neurons. These findings contribute to elucidation of the role played by NE during the positive feedback of ovarian steroids.

Endogenous opioids and ventilatory responses to hypercapnia in normal humans

1985 ◽  
Vol 58 (5) ◽  
pp. 1415-1420 ◽  
Author(s):  
S. E. Weinberger ◽  
R. A. Steinbrook ◽  
D. B. Carr ◽  
E. R. von Gal ◽  
J. E. Fisher ◽  
...  
Keyword(s):  
Opioid Peptides ◽  
Endogenous Opioids ◽  
Opiate Antagonist ◽  
Endogenous Opioid Peptides ◽  
Short Term ◽  
Endogenous Opioid ◽  
Beta Endorphin ◽  
Ventilatory Responses ◽  
Normal Humans

Though administration of opioid peptides depresses ventilation and ventilatory responsiveness, the role of endogenous opioid peptides in modulating ventilatory responsiveness is not clear. We studied the interaction of endogenous opioids and ventilatory responses in 12 adult male volunteers by relating hypercapnic responsiveness to plasma levels of immunoactive beta-endorphin and by administering the opiate antagonist naloxone. Ventilatory responsiveness to hypercapnia was not altered by pretreatment with naloxone, and this by itself suggests that endogenous opioids have no role in modulating this response. However, there was an inverse relationship between basal levels of immunoactive beta-endorphin in plasma and ventilatory responsiveness to CO2. Furthermore, plasma beta-endorphin levels rose after short-term hypercapnia but only when subjects had been pretreated with naloxone. We conclude that measurement of plasma endorphin levels suggests relationships between endogenous opioid peptides and ventilatory responses to CO2 that are not apparent in studies limited to assessing the effect of naloxone.

Opioids and breathing

1985 ◽  
Vol 59 (6) ◽  
pp. 1675-1685 ◽  
Author(s):  
T. V. Santiago ◽  
N. H. Edelman
Keyword(s):  
Pain Modulation ◽  
Endogenous Opioids ◽  
Opiate Antagonist ◽  
Endogenous Opioid ◽  
Disease States ◽  
Specific Effects ◽  
Neonatal Life ◽  
Opiate Drugs ◽  
Recent Developments

This review summarizes recent developments on the effects of opiate drugs and the various endogenous opioid peptides on breathing. These developments include demonstration of receptors and site-specific effects of application of opioids in the pons and medulla, demonstration of variable tolerance of respiratory responses in addicted individuals as well as their offspring, and demonstration of an endogenous opioid influence on breathing in early neonatal life and in certain physiological settings and disease states. The validity and limitations of using naloxone as a tool to uncover postulated endogenous opioid influences are also discussed as well as the potential problems imposed by the various settings in which this opiate antagonist drug is used. It is concluded that some parallelism exists between the role of endogenous opioids in pain modulation and their role in respiration especially in adults. Although more studies are needed especially with regard to defining specific effects of the various opioid receptors and ligands, it is felt that the effects of endogenous opioids on the control of breathing will probably be one of modulating the responses to drugs or nociceptive respiratory stimuli through inhibitory pathways.

Control of luteinizing hormone secretion in ewes by endogenous opioids and the dopaminergic system during short seasonal anoestrus: rôle of plane of nutrition

1997 ◽  
Vol 65 (2) ◽  
pp. 217-224 ◽  
Author(s):  
F. Forcada ◽  
J. M. Lozano ◽  
J. A. Abecia ◽  
L. Zarazaga
Keyword(s):  
Luteinizing Hormone ◽  
Receptor Antagonist ◽  
Dopaminergic System ◽  
Hormone Secretion ◽  
Pulse Frequency ◽  
Endogenous Opioids ◽  
Endogenous Opioid ◽  
Luteinizing Hormone Secretion ◽  
Lh Secretion

AbstractThe role of endogenous opioids and the dopaminergic system on the inhibition of luteinizing hormone (LH) secretion during early and late anoestrus, together with its modulation by the plane of nutrition were investigated in ewes with a short anoestrous season. In early anoestrus (22 March; day 0), two groups of ovariectomized, oestradiol-treated adult Rasa Aragonesa ewes, maintained under natural photoperiod at 41°N, were given enough food to provide 1·4 × (high; H; no. = 6) or 0·5 × (low; L; no. = 6) energy requirements for maintenance. The effects of administration of the opiate receptor antagonist naloxone (1 mg/kg at four 1-h intervals) (day 15) and of the dopaminergic2 receptor antagonist pimozide (0·08 mg/kg) (day 21) on LH secretion were assessed. A second experiment was carried out in late anoestrus (21 June) using the same protocol. A significant increase in LH pulse frequency after naloxone treatment for both H and L groups was detected in late anoestrus. Number ofLH pulses after naloxone injections in early anoestrus also increased in H (P < 0·05) and L ewes (P = 0·08). The effect of pimozide injection on mean LH pulse frequency was greater in early than in late anoestrus, especially in ewes receiving a high plane of nutrition (P < 0·05 and P = 0·07 for H and L ewes, respectively in April and P = 0·07 for H ewes in July). A significant increase of LH pulse amplitude was also detected in early anoestrus in H ewes (P < 0·01). These results provide evidence that endogenous opioid mechanisms are involved in the inhibition ofLH pulsatile release both in early and late anoestrus in ewes with a short seasonal anoestrus. The ability of pimozide to increase LH pulse frequency in early anoestrus could be enhanced by a high plane of nutrition in the breed studied.

Growth hormone, prolactin and cortisol nyctohemeral variations during naloxone-induced opiate receptor blockade in man

1982 ◽  
Vol 100 (3) ◽  
pp. 321-326 ◽  
Author(s):  
G. Delitala ◽  
M. Giusti ◽  
G. Rodriguez ◽  
G. Mazzocchi ◽  
S. Ferrini ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Bolus Injection ◽  
Opiate Receptors ◽  
Opiate Receptor ◽  
Normal Male ◽  
Opiate Antagonist ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Blood Specimens

Abstract. To evaluate the role of endogenous opioid peptides in prolactin (Prl), growth hormone (GH) and cortisol neuroregulation, 50 mg of the opiate antagonist naloxone was infused over 24 h to 6 normal male volunteers. An additional naloxone dose (5 mg) was given iv as a bolus injection at 20.00 h. Blood specimens were collected hourly by means of a portable constant withdrawal pump. Naloxone failed to alter 24 h secretion of GH and Prl. The sleep-related GH and Prl rise was also unaffected by the opiate blocker. Moreover, naloxone failed to alter the circadian rhythm of cortisol and its 24 h concentration. The results do not suggest a major role of opiate receptors in spontaneous GH, Prl and cortisol secretion in man.

Role of male novelty and familiarity in male-induced LH secretion in female sheep

2012 ◽  
Vol 24 (4) ◽  
pp. 523 ◽  
Author(s):  
T. Jorre de St Jorre ◽  
P. A. R. Hawken ◽  
G. B. Martin
Keyword(s):  
Lh Surge ◽  
Gonadotrophin Secretion ◽  
Lh Secretion ◽  
Female Sheep

Ewes supposedly need to be separated from rams before male stimuli can increase gonadotrophin secretion and induce ovulation. In the present study, we investigated the LH response of ewes to ‘novel’ and ‘familiar’ rams after varying periods of separation. In Experiment 1, ewes (n = 8 per treatment) were separated from familiar rams for 15 min or 1 month and then exposed to either familiar rams, novel rams or novel wethers. After 15 min or 1 month of separation, exposure to novel rams increased pulsatile LH secretion (P < 0.05) and induced an LH surge in all ewes whereas exposure to familiar rams or novel wethers had no effect on LH secretion (P > 0.1). After 1 month of separation, re-exposure to the same familiar rams increased pulsatile LH secretion (P < 0.05) in six of eight ewes, but only induced an LH surge in two of eight ewes. In Experiment 2, familiar rams were removed and returned after 15 min, 1 day or 17 days (n = 5 per treatment). None of these treatments affected LH secretion. We conclude that separation of ewes from rams is a prerequisite for familiar rams to increase LH secretion, but is not necessary if the rams are novel.

scholarly journals KNDy (Kisspeptin/Neurokinin B/Dynorphin) Neurons Are Activated during Both Pulsatile and Surge Secretion of LH in the Ewe

Endocrinology ◽  
2012 ◽  
Vol 153 (11) ◽  
pp. 5406-5414 ◽  
Author(s):  
Christina M. Merkley ◽  
Katrina L. Porter ◽  
Lique M. Coolen ◽  
Stanley M. Hileman ◽  
Heather J. Billings ◽  
...  
Keyword(s):  
Negative Feedback ◽  
Positive Feedback ◽  
Neurokinin B ◽  
Lh Surge ◽  
Short And Long Term ◽  
Positive And Negative Feedback ◽  
Kndy Neurons ◽  
Lh Secretion

Abstract KNDy (kisspeptin/neurokinin B/dynorphin) neurons of the arcuate nucleus (ARC) appear to mediate the negative feedback actions of estradiol and are thought to be key regulators of pulsatile LH secretion. In the ewe, KNDy neurons may also be involved with the positive feedback actions of estradiol (E2) to induce the LH surge, but the role of kisspeptin neurons in the preoptic area (POA) remains unclear. The goal of this study was to identify which population(s) of kisspeptin neurons is (are) activated during the LH surge and in response to the removal of E2-negative feedback, using Fos as an index of neuronal activation. Dual-label immunocytochemistry for kisspeptin and Fos was performed on sections containing the ARC and POA from ewes during the luteal phase of the estrous cycle, or before or after the onset of the LH surge (experiment 1), and from ovary-intact, short-term (24 h) and long-term (&gt;30 d) ovariectomized (OVX) ewes in anestrus (experiment 2). The percentage of kisspeptin neurons expressing Fos in both the ARC and POA was significantly higher during the LH surge. In contrast, the percentage of kisspeptin/Fos colocalization was significantly increased in the ARC, but not POA, after both short- and long-term E2 withdrawal. Thus, POA kisspeptin neurons in the sheep are activated during, and appear to contribute to, E2-positive feedback, whereas ARC kisspeptin (KNDy) neurons are activated during both surge and pulsatile modes of secretion and likely play a role in mediating both positive and negative feedback actions of E2 on GnRH secretion in the ewe.

Interaction of dopaminergic and antiserotoninergic drugs in the control of prolactin and LH release in normal women

1980 ◽  
Vol 93 (3) ◽  
pp. 271-276 ◽  
Author(s):  
Antonio E. Pontiroli ◽  
Miriam Alberetto ◽  
Gabriele Pellicciotta ◽  
Emilio De Castro e Silva ◽  
Anna De Pasqua ◽  
...  
Keyword(s):  
Experimental Animal ◽  
Lh Surge ◽  
Inhibiting Effect ◽  
Lh Release ◽  
Normal Women ◽  
Plasma Prl ◽  
Lh Secretion

Abstract. Prolactin (Prl) release, both in the experimental animal and in man, is stimulated by serotonin (5HT) and inhibited by dopamine (DA). Data also suggest that LH release in the animal is stimulated by norepinephrine and inhibited by DA. The role of 5HT in the control of LH release is less clear. It would appear to stimulate episodic LH release and to inhibit the LH surge at the pro-oestrus in animals, but the effect of 5HT on LH release has not yet been evaluated in man. In the present paper we have studied the effect of various DA-ergic drugs (DA, iv 1-dopa, po 1-dopa and bromoergocriptine) and of two anti-5HT drugs, metergoline and methysergide, on Prl and LH release in normal women. DA-ergic drugs lowered plasma Prl and LH levels; anti-5HT drugs, at doses able to lower Prl levels, did not affect basal LH release nor the inhibiting effect of iv 1-dopa on LH release. These data indicate that DA inhibits both LH and Prl release in normal women, and that 5HT stimulates Prl release but is not involved in the regulation of LH secretion. The fact that, at variance to all the DA-ergic drugs used, the two anti-5HT drugs did not vary LH release, suggests that metergoline and methysergide are devoid of DA-ergic activity in man, at least at the doses able to inhibit Prl release.

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