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

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

scholarly journals Regulation of Luteinizing Hormone and Catecholamine Release

1984 ◽  
Author(s):  
◽  
Benjamin Adler
Keyword(s):  
Median Eminence ◽  
Positive Feedback ◽  
Ovarian Hormones ◽  
Ovariectomized Rats ◽  
Ovarian Hormone ◽  
Synthesis Inhibitor ◽  
Feedback Effects ◽  
Lh Surge ◽  
Lh Release ◽  
Lh Secretion

These studies tested the interrelated hypotheses that the ovarian hormones produce their positive feedback effects on luteinizing hormone (LH) secretion through activation of noradrenergic and adrenergic systems in specific hypothalamic regions. Furthermore, the ovarian hormones may alter the activity of opioid neuropeptide and Gamma-Aminobutyric Acid (GABA) systems to produce these alterations in catecholamine transmission and gonadotropin secretion. Radioimmunoassays were utilized to determine plasma LH and median eminence LHRH, and hypothalamic catecholamine concentrations were measured by radioenzymatic assay. The first two studies tested whether epinephrine (EPI) synthesis inhibition blocks the accumulation of median eminence LHRH that precedes the ovarian hormone-induced LH surge and also to test whether the stimulatory ovarian hormone regimen enhances the activity of hypothalamic EPI systems. Ovariectomized rats were primed with estradiol (EB), followed 2 days later by progesterone (Prog.). Animals were treated before Prog, administration with saline, one of the EPI synthesis inhibitors SKF 64139 or LY 78335, or the norepinephrine (NE) synthesis inhibitor, FLA-63. The catecholamine synthesis inhibitors blocked or delayed the LH surge. FLA-63 completely prevented the accumulation of LHRH in the median eminence that preceded the rise in LH release. However, selective reduction in EPI levels with SKF 64139 only partially prevented this increase in LHRH. A second EPI synthesis inhibitor, LY 78335, delayed both the LH surge and the rise in LHRH. In a second experiment, the administration of EB plus Prog, to ovariectomized rats increased the alpha-methyltyrosine (aMT) induced depletion of EPI in the medial basal hypothalamus (MBH). The depletion of NE after synthesis inhibition was enhanced in both the MBH and preoptic-anterior hypothalamus (POA). Experiments 3 and 4 examined a possible mechanism underlying these ovarian hormone effects on LH release and catecholamine activity. These studies tested whether the opiate antagonist, naloxone, which increases LH release, enhances the activity of NE and EPI neurons in the hypothalamus, and also tested whether morphine, an opiate agonist which decreases LH release, depresses the activity of hypothalamic NE and EPI activity. Administration of naloxone to EB-primed rats increased LH release and potentiated the depletion of NE in the POA and MBH, and enhanced the decline of EPI and dopamine (DA) in the MBH, suggesting increased catecholamine activity in these regions. Administration of the opiate agonist, morphine, to rats pretreated with EB and Prog., decreased LH and decreased the depletion of the catecholamines in the POA and MBH, suggesting reduced activity. In most cases, naloxone antagonized the inhibitory effect of morphine. Experiments 3, 6, and 7 examined the involvement of (GABA) systems in the positive feedback effects of EB and Prog, on LHRH and LH release. These studies tested 1) the effects of GABAergic drugs on the LH surge induced by EB and Prog., 2) whether GABA agonists reduce NE and EPI activity in the hypothalamus, and 3) whether a GABA agonist prevents the accumulation of median eminence LHRH induced by EB and Prog. Ovariectomized rats received the stimulatory EB plus Prog, treatment. Simultaneously with Prog., rats received either saline, the barbiturate, phenobarbital, the GABAg agonist, baclofen, the GABA^ agonist, muscimol, or either the GABA^ antagonist, bicuculline, or the putative GABAg antagonist, 5-aminovalerate. Additional experiments tested the effects of the GABA drugs on LH release in ovariectomized, hormonally untreated rats and in response to exogenous LHRH. The LH surge induced by EB+Prog. was blocked by treatment with either baclofen, muscimol, or phenobarbital. Bicuculline was ineffective in preventing the effect of baclofen and phonobarbital but partially prevented the effect of muscimol. Neither baclofen nor muscimol significantly affected LH release in hormonally untreated, ovariectomized rats or in rats receiving LHRH administration. In the results of Experiment 6, in EB plus Prog.-treated rats, baclofen and muscimol significantly reduced the concentrations of EPI and NE in the POA and MBH and prevented their decline after administration of otMT, suggesting decreased catecholamine transmission. In Experiment 7, rats were primed with the ovarian hormones and received, concurrently with Prog., either saline, or baclofen. The GABAg agonist, baclofen, blocked the LH surge and selectively increased LHRH concentrations. Experiment 8 tested 1) whether baclofen reverses the enhancement of LH release and catecholamine activity produced by naloxone, and 2) whether the opiate antagonist, nalmefene, prevents the blockade of the LH surge produced by baclofen. In the first study of Experiment 8, naloxone increased LH release and enhanced catecholamine activity in EB-primed rats. Baclofen was unable to reverse these effects. In the second study, baclofen administration to EB plus P treated rats blocked the LH surge and concomitant administration of nalmefene was unable to prevent this effect of baclofen. These results suggest that: 1) the ovarian hormones activate both NE and EPI systems to stimulate the early afternoon rise of LHRH in the median eminence and to induce the subsequent LH surge, 2) the ovarian hormones may produce their positive feedback effects on LH secretion by removing an inhibitory GABA or opioid neuropeptide influence on catecholamine transmission, allowing NE and EPI to stimulate LHRH, and subsequently, LH release, and 3) these modulatory actions of GABA and opiates may represent effects of two parallel, yet independent hypothalamic systems which regulate catecholamine neurotransmission and subsequently LH secretion.

scholarly journals Pup removal suppresses estrogen-induced surges of LH secretion and activation of GnRH neurons in lactating rats

2006 ◽  
Vol 191 (1) ◽  
pp. 339-348 ◽  
Author(s):  
Atsushi Fukushima ◽  
Ping Yin ◽  
Maho Ishida ◽  
Nobuhiro Sugiyama ◽  
Jun Arita
Keyword(s):  
Third Ventricle ◽  
Acute Effect ◽  
Suppressive Effect ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Indwelling Catheter ◽  
Lh Surge ◽  
Gnrh Neurons ◽  
Double Immunohistochemical Staining ◽  
Lh Secretion

During lactation, the suckling stimulus exerts profound influences on neuroendocrine regulation in nursing rats. We examined the acute effect of pup removal on the estrogen-induced surge of LH secretion in ovariectomized lactating rats. Lactating and nonlactating cyclic female rats were given an estradiol-containing capsule after ovariectomy, and blood samples were collected through an indwelling catheter for serum LH determinations. In lactating, freely suckled ovariectomized rats, estrogen treatment induced an afternoon LH surge with a magnitude and timing comparable to those seen in nonlactating rats. Removal of pups from the lactating rats at 0900, 1100, or 1300 h, but not at 1500 h, suppressed the estrogen-induced surge that normally occurs in the afternoon of the same day. The suppressive effect of pup removal at 0900 h was completely abolished when the pups were returned by 1400 h. In contrast, pup removal was ineffective in abolishing the stimulatory effect of progesterone on LH surges. Double immunohistochemical staining for gonadotropin-releasing hormone (GnRH) and c-Fos, a marker for neuronal activation, revealed a decrease, concomitantly with the suppression of LH surges, in the number of c-Fos-immunoreactive GnRH neurons in the preoptic regions of nonsuckled rats. An LH surge was restored in nonsuckled rats when 0.1 μg oxytocin was injected into the third ventricle three times at 1-h intervals during pup removal. These results suggest that the GnRH surge generator of lactating rats requires the suckling stimulus that is not involved in nonlactating cyclic female rats.

scholarly journals KNDy Neurons Modulate the Magnitude of the Steroid-Induced Luteinizing Hormone Surges in Ovariectomized Rats

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 4200-4213 ◽  
Author(s):  
Cleyde V. Helena ◽  
Natalia Toporikova ◽  
Bruna Kalil ◽  
Andrea M. Stathopoulos ◽  
Veronika V. Pogrebna ◽  
...  
Keyword(s):  
Negative Feedback ◽  
Arcuate Nucleus ◽  
Ovariectomized Rats ◽  
Neurokinin B ◽  
Lh Surge ◽  
Neuronal Populations ◽  
Lh Release ◽  
Positive And Negative Feedback ◽  
Kndy Neurons ◽  
Lh Secretion

Kisspeptin is the most potent stimulator of LH release. There are two kisspeptin neuronal populations in the rodent brain: in the anteroventral periventricular nucleus (AVPV) and in the arcuate nucleus. The arcuate neurons coexpress kisspeptin, neurokinin B, and dynorphin and are called KNDy neurons. Because estradiol increases kisspeptin expression in the AVPV whereas it inhibits KNDy neurons, AVPV and KNDy neurons have been postulated to mediate the positive and negative feedback effects of estradiol on LH secretion, respectively. Yet the role of KNDy neurons during the positive feedback is not clear. In this study, ovariectomized rats were microinjected bilaterally into the arcuate nucleus with a saporin-conjugated neurokinin B receptor agonist for targeted ablation of approximately 70% of KNDy neurons. In oil-treated animals, ablation of KNDy neurons impaired the rise in LH after ovariectomy and kisspeptin content in both populations. In estradiol-treated animals, KNDy ablation did not influence the negative feedback of steroids during the morning. Surprisingly, KNDy ablation increased the steroid-induced LH surges, accompanied by an increase of kisspeptin content in the AVPV. This increase seems to be due to lack of dynorphin input from KNDy neurons to the AVPV as the following: 1) microinjections of a dynorphin antagonist into the AVPV significantly increased the LH surge in estradiol-treated rats, similar to KNDy ablation, and 2) intra-AVPV microinjections of dynorphin in KNDy-ablated rats restored LH surge levels. Our results suggest that KNDy neurons provide inhibition to AVPV kisspeptin neurons through dynorphin and thus regulate the amplitude of the steroid-induced LH surges.

Dissociation between the ovarian factors controlling sexual receptivity and preovulatory secretion of LH in cyclic female rats

1987 ◽  
Vol 112 (1) ◽  
pp. 133-138 ◽  
Author(s):  
P. Södersten ◽  
P. Eneroth
Keyword(s):  
Sexual Behaviour ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Sexual Receptivity ◽  
Serum Progesterone ◽  
Lh Surge ◽  
Oestradiol Benzoate ◽  
Lh Release ◽  
Lh Secretion ◽  
Intact Rats

ABSTRACT Ovariectomy and treatment with oestradiol benzoate (10 μg OB) on the day before behavioural oestrus eliminated the preovulatory surge of LH and reduced the level of sexual receptivity on the following day. Sexual behaviour, but not the LH surge, was restored by progesterone (0·5 mg) given 18 h later. Injection of OB on the day after behavioural oestrus induced a small release of LH and normal sexual behaviour on the following day. Ovariectomy on the day after behavioural oestrus reduced the stimulatory effect of OB on sexual behaviour and eliminated its weakly stimulatory effect on LH release. Sexual behaviour, but not the small LH surge, was restored in these animals by progesterone (0·5 mg) given 18 h later. Treatment of rats ovariectomized 2 days before the day of the LH surge with implants containing oestradiol or injections of oestradiol (1 μg) induced LH surges but the amplitudes of these LH surges were much smaller than those of the normal LH surge. Treatment of intact rats with OB increased serum progesterone levels 24 h later, an effect which was eliminated by ovariectomy. Injections of LH (20 μg) into intact rats on the day after behavioural oestrus also increased serum progesterone concentrations but failed to stimulate sexual behaviour. It is suggested that OB treatment of intact rats on the day after behavioural oestrus stimulates sexual behaviour by inducing a surge of LH secretion which activates ovarian secretion of progesterone. Thus, oestrogen and progesterone but not the LH surge are essential for sexual behaviour. Whereas oestradiol and progesterone restore normal sexual behaviour in ovariectomized rats, additional ovarian factors may be required for induction of normal LH surges. J. Endocr. (1987) 112, 133–138

Evidence for an increased opioid inhibition of LH secretion in hyperprolactinaemic ovariectomized rats

1984 ◽  
Vol 101 (1) ◽  
pp. 57-61 ◽  
Author(s):  
D. A. Carter ◽  
J. S. Cooper ◽  
S. E. Inkster ◽  
S. A. Whitehead
Keyword(s):  
Positive Feedback ◽  
Day Treatment ◽  
Inhibitory Effect ◽  
Ovariectomized Rats ◽  
Dopamine Antagonist ◽  
Similar Treatment ◽  
Lh Surge ◽  
Lh Release ◽  
Ovine Prolactin ◽  
Lh Secretion

ABSTRACT The effects of acute and sub-chronic hyperprolactinaemia on the positive feedback action of progesterone in oestrogen-primed ovariectomized rats have been compared. A single injection of ovine prolactin administered with progesterone had no effect on the LH surge measured 5 h later although hyperprolactinaemia induced by 5-day treatment with the dopamine antagonist, domperidone, markedly attenuated the surge. Repeated injections of naloxone (5 mg/kg) during the development of the progesterone-stimulated LH surge completely reversed this inhibitory effect of hyperprolactinaemia, but had no apparent effect on the positive feedback action in control animals. In oestrogen-primed animals similar treatment with naloxone (0·4 and 5 mg/kg) stimulated LH secretion but the increase was significantly smaller than that observed after injecting progesterone. It is suggested that hyperprolactinaemia increases the inhibitory opioid modulation of LH release and that this effect is responsible for the impairment of the positive feedback action of progesterone. J. Endocr. (1984) 101, 57–61

Vasoactive intestinal peptide inhibits the steroid-induced LH surge in the ovariectomized rat

1992 ◽  
Vol 133 (3) ◽  
pp. 433-437 ◽  
Author(s):  
R. F. Weick ◽  
K. M. Stobie
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Critical Period ◽  
Control Sample ◽  
Ovariectomized Rats ◽  
Lh Surge ◽  
The Third ◽  
Oestradiol Benzoate ◽  
Short Time ◽  
Lh Secretion ◽  
Secretion Rates

ABSTRACT The LH surge was induced in ovariectomized rats by sequential treatment with oestradiol benzoate and progesterone. Vasoactive intestinal peptide (VIP) or saline was infused into the third cerebral ventricle from 13.30 to 16.30 h on the afternoon of the anticipated LH surge. Two blood samples were taken by jugular puncture from each animal, one at 12.00 h as a control sample and the other at 16.00, 18.00, 20.00 or 22.00 h. Saline-infused animals showed a normal LH surge, with mean plasma LH concentrations reaching a peak at 18.00 h, declining by 20.00 h and reaching control (12.00 h) levels by 22.00 h. Plasma LH in animals infused with VIP was not significantly higher than control levels at 16.00 or 18.00 h. By 20.00 h, mean LH levels in VIP-infused rats had risen to the levels seen at that time in saline-infused rats, and by 22.00 h LH had returned to control levels in VIP-infused animals. We interpret these findings to mean that VIP inhibits LH secretion during the LH surge. It does not block the surge completely, as pentobarbital during the critical period would have done; nor does VIP appear to affect the timing of the LH surge. Rather, VIP inhibits the increased LH secretion rates of the LH surge only during the period of VIP treatment and for a short time afterward. Journal of Endocrinology (1992) 133, 433–437

scholarly journals Understanding the regulation of pituitary progesterone receptor expression and phosphorylation

Reproduction ◽  
2015 ◽  
Vol 149 (6) ◽  
pp. 615-623 ◽  
Author(s):  
Ana Gordon ◽  
José C Garrido-Gracia ◽  
Rafaela Aguilar ◽  
José E Sánchez-Criado
Keyword(s):  
Progesterone Receptor ◽  
Inhibitory Action ◽  
Receptor Expression ◽  
Potential Mechanism ◽  
Post Translational Modification ◽  
Lh Surge ◽  
Biphasic Effect ◽  
Blotting Technique ◽  
Lh Secretion

Administration of human FSH (hFSH) during the diestrus phase in cyclic rats is followed by a reduction in the preovulatory LH surge. This inhibitory action of FSH involves a decrease in the stimulatory effect of gonadotrope progesterone receptor (PR) activation, in a ligand-dependent (progesterone) and -independent (GNRH) manner. PR activation and action are mandatory for LH surge, and are dependent on the phosphorylation of serine (Ser) residues. Together with this post-translational modification, PR is marked for downregulation by proteasome machinery. These experiments used the western blotting technique to measure pituitary expression of PR-A and PR-B isoforms and phosphorylation levels of Ser294 and Ser400 PR-B in rats bearing i) hFSH treatment or ii) PR downregulation. Treatment with hFSH reduced LH secretion and increased that of estradiol in proestrus afternoon. hFSH injections, without altering PR-A and PR-B content or ratio, caused a reduction in phosphorylation of Ser294 and Ser400 but only when pituitaries were previously challenged with progesterone or GNRH for 2 h. However, while pSer294 levels increased after 2 h of pituitary incubation with progesterone or GNRH, those of pSer400 were not modified by thesein vitrotreatments. Finally, progesterone had a biphasic effect: in 2-h incubations increased pituitary PR-A and PR-B content, but after 8 h caused downregulation and altered PR-A:PR-B ratio. The results provide a potential mechanism through which LH levels are decreased by hFSH administration and better understanding of the control of PR expression and phosphorylation in rat pituitaries.

Opiate suppression of LH secretion involves central receptors different from those mediating opiate effects on prolactin secretion

1987 ◽  
Vol 114 (3) ◽  
pp. 469-476 ◽  
Author(s):  
D. G. Pfeiffer ◽  
A. Pfeiffer ◽  
O. F. X. Almeida ◽  
A. Herz
Keyword(s):  
Opiate Receptors ◽  
Opiate Receptor ◽  
Prolactin Secretion ◽  
Ovariectomized Rats ◽  
Dependent Manner ◽  
Methyl Ester Derivative ◽  
High Doses ◽  
Lh Secretion

ABSTRACT The involvement of μ- and κ-opiate receptors in the regulation of LH and prolactin secretion was investigated in long-term ovariectomized rats using selective opiate receptor agonists and antagonists. The μ-agonists morphine and [d-Ala2,MePhe4,Gly5-ol]-enkephalin (DAGO) suppressed LH levels in a dose-related manner. The benzomorphane (−)-5,9-dimethyl-2′-hydroxy-2-(tetrahydrofurfuryl)-6,7-benzomorphan tartrate (MR 2034; a designated κ-agonist) also suppressed LH levels, whereas another benzomorphane κ-agonist (−)-5,9-dimethyl-2′-hydroxy-2-(2-methoxy-propyl)-6,7-benzomorphan hydrobromide (MRZ 2549) had no effect on the levels of this hormone. Pretreatment with the highly selective μ-antagonist β-funaltrexamine (β-FNA), the fumarate methyl ester derivative of naltrexone, blocked the actions of both μ-agonists and MR 2034, indicating that opiate suppression of LH secretion is mediated by μ-receptors. This was further confirmed by in-vitro studies: the KCl-induced release of LHRH from perifused hypothalami obtained from ovariectomized rats was significantly reduced by DAGO but not by MRZ 2549. Prolactin secretion was stimulated in a dose-dependent manner by both μ- and κ-agonists. The stimulation caused by morphine and DAGO was antagonized by β-FNA, whereas that caused by the κ-agonists MR 2034 and MZR 2549 was resistant to blockade by β-FNA but not by naloxone (an antagonist which blocks all classes of opiate receptors when given in high doses). Thus prolactin secretion seems to be regulated by both μ- and κ-opiate receptors, whereas the effects on LH secretion seem to involve μ-receptors only. J. Endocr. (1987) 114, 469–476

scholarly journals The Increase in Signaling by Kisspeptin Neurons in the Preoptic Area and Associated Changes in Clock Gene Expression That Trigger the LH Surge in Female Rats Are Dependent on the Facilitatory Action of a Noradrenaline Input

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 323-335 ◽  
Author(s):  
Bruna Kalil ◽  
Aline B. Ribeiro ◽  
Cristiane M. Leite ◽  
Ernane T. Uchôa ◽  
Ruither O. Carolino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Median Eminence ◽  
Preoptic Area ◽  
Clock Genes ◽  
Third Ventricle ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Lh Surge ◽  
Clock Gene Expression

Abstract In rodents, kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) of the preoptic area are considered to provide a major stimulatory input to the GnRH neuronal network that is responsible for triggering the preovulatory LH surge. Noradrenaline (NA) is one of the main modulators of GnRH release, and NA fibers are found in close apposition to kisspeptin neurons in the RP3V. Our objective was to interrogate the role of NA signaling in the kisspeptin control of GnRH secretion during the estradiol induced LH surge in ovariectomized rats, using prazosin, an α1-adrenergic receptor antagonist. In control rats, the estradiol-induced LH surge at 17 hours was associated with a significant increase in GnRH and kisspeptin content in the median eminence with the increase in kisspeptin preceding that of GnRH and LH. Prazosin, administered 5 and 3 hours prior to the predicted time of the LH surge truncated the LH surge and abolished the rise in GnRH and kisspeptin in the median eminence. In the preoptic area, prazosin blocked the increases in Kiss1 gene expression and kisspeptin content in association with a disruption in the expression of the clock genes, Per1 and Bmal1. Together these findings demonstrate for the first time that NA modulates kisspeptin synthesis in the RP3V through the activation of α1-adrenergic receptors prior to the initiation of the LH surge and indicate a potential role of α1-adrenergic signaling in the circadian-controlled pathway timing of the preovulatory LH surge.

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