scholarly journals The Dorsomedial Suprachiasmatic Nucleus Times Circadian Expression of Kiss1 and the Luteinizing Hormone Surge

Endocrinology ◽  
2012 ◽  
Vol 153 (6) ◽  
pp. 2839-2850 ◽  
Author(s):  
Benjamin L. Smarr ◽  
Emma Morris ◽  
Horacio O. de la Iglesia
Keyword(s):  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Phase Coherence ◽  
Reproductive Disorders ◽  
Lh Surge ◽  
Circadian Expression ◽  
Neural Input ◽  
Periventricular Nucleus ◽  
Gnrh Neurons ◽  
Neuronal Oscillators

Ovulation in mammals is gated by a master circadian clock in the suprachiasmatic nucleus (SCN). GnRH neurons represent the converging pathway through which the brain triggers ovulation, but precisely how the SCN times GnRH neurons is unknown. We tested the hypothesis that neurons expressing kisspeptin, a neuropeptide coded by the Kiss1 gene and necessary for the activation of GnRH cells during ovulation, represent a relay station for circadian information that times ovulation. We first show that the circadian increase of Kiss1 expression, as well as the activation of GnRH cells, relies on intact ipsilateral neural input from the SCN. Second, by desynchronizing the dorsomedial (dm) and ventrolateral (vl) subregions of the SCN, we show that a clock residing in the dmSCN acts independently of the light-dark cycle, and the vlSCN, to time Kiss1 expression in the anteroventral periventricular nucleus of the hypothalamus and that this rhythm is always in phase with the LH surge. In addition, we show that although the timing of the LH surge is governed by the dmSCN, its amplitude likely depends on the phase coherence between the vlSCN and dmSCN. Our results suggest that whereas dmSCN neuronal oscillators are sufficient to time the LH surge through input to kisspeptin cells in the anteroventral periventricular nucleus of the hypothalamus, the phase coherence among dmSCN, vlSCN, and extra-SCN oscillators is critical for shaping it. They also suggest that female reproductive disorders associated with nocturnal shift work could emerge from the desynchronization between subregional oscillators within the master circadian clock.

scholarly journals Vasoactive Intestinal Peptide Modulation of the Steroid-Induced LH Surge Involves Kisspeptin Signaling in Young but Not in Middle-Aged Female Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (6) ◽  
pp. 2222-2232 ◽  
Author(s):  
Alexander S. Kauffman ◽  
Yan Sun ◽  
Joshua Kim ◽  
Azim R. Khan ◽  
Jun Shu ◽  
...  
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Suprachiasmatic Nucleus ◽  
Reproductive Age ◽  
Female Rats ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Middle Aged ◽  
Lh Surge ◽  
Young Females ◽  
Gnrh Neurons

Age-related LH surge dysfunction in middle-aged rats is characterized, in part, by reduced responsiveness to estradiol (E2)-positive feedback and reduced hypothalamic kisspeptin neurotransmission. Vasoactive intestinal peptide (VIP) neurons in the suprachiasmatic nucleus project to hypothalamic regions that house kisspeptin neurons. Additionally, middle-age females express less VIP mRNA in the suprachiasmatic nucleus on the day of the LH surge and intracerebroventricular (icv) VIP infusion restores LH surges. We tested the hypothesis that icv infusion of VIP modulates the LH surge through effects on the kisspeptin and RFamide-related peptide-3 (RFRP-3; an estradiol-regulated inhibitor of GnRH neurons) neurotransmitter systems. Brains were collected for in situ hybridization analyses from ovariectomized and ovarian hormone-primed young and middle-aged females infused with VIP or saline. The percentage of GnRH and Kiss1 cells coexpressing cfos and total Kiss1 mRNA were reduced in saline-infused middle-aged compared with young females. In young females, VIP reduced the percentage of GnRH and Kiss1 cells coexpressing cfos, suggesting that increased VIP signaling in young females adversely affected the function of Kiss1 and GnRH neurons. In middle-aged females, VIP increased the percentage of GnRH but not Kiss1 neurons coexpressing cfos, suggesting VIP affects LH release in middle-aged females through kisspeptin-independent effects on GnRH neurons. Neither reproductive age nor VIP affected Rfrp cell number, Rfrp mRNA levels per cell, or coexpression of cfos in Rfrp cells. These data suggest that VIP differentially affects activation of GnRH and kisspeptin neurons of female rats in an age-dependent manner.

scholarly journals Genetic Deletion of Esr1 in the Mouse Preoptic Area Disrupts the LH Surge and Estrous Cyclicity

Endocrinology ◽  
2019 ◽  
Vol 160 (8) ◽  
pp. 1821-1829 ◽  
Author(s):  
Robert Porteous ◽  
Allan E Herbison
Keyword(s):  
Estrogen Receptor ◽  
Third Ventricle ◽  
Estrogen Receptor Α ◽  
Adeno Associated Virus ◽  
Estrous Cycles ◽  
Lh Surge ◽  
Periventricular Nucleus ◽  
Gnrh Neurons ◽  
Estrous Cyclicity ◽  
Periventricular Area

Abstract Estrogen receptor α (ESR1) is critical for the generation of the preovulatory LH surge. Experiments in rodents have indicated a role for neurons located in the anteroventral periventricular area and preoptic periventricular nucleus [termed the rostral periventricular area of the third ventricle (RP3V)] in surge generation. In the current study, we aimed to examine whether ESR1 expressed by RP3V neurons was necessary for the LH surge. The estrous cycles of mice with estrogen receptor α (Esr1) exon 3 flanked by LoxP sites (Esr1 flox) and controls were monitored before and after bilateral stereotactic injection of adeno-associated virus encoding Cre recombinase into the RP3V. This resulted in 84% and 72% decreases in ESR1-immunoreactive cell numbers in the anteroventral periventricular area and preoptic periventricular nucleus, respectively, with no changes in the arcuate nucleus. Beginning three weeks after the adeno-associated virus injection, Esr1 flox mice began to show a loss of estrous cyclicity going, primarily, into constant estrus. Wild-type mice and Esr1 flox mice with injections outside the RP3V or unilateral ablations of ESR1 continued to exhibit normal estrous cycles. Mice were then gonadectomized and given an estradiol replacement regimen to generate the LH surge. This resulted in an absence of cFOS expression in GnRH neurons (1 ± 1% vs 28 ± 4% of GnRH neurons; P < 0.01) and markedly reduced LH surge levels (2.5 ± 0.6 vs 9.1 ± 1.0 ng/mL; P < 0.01) in Esr1 flox mice compared with controls. These results demonstrate that neurons expressing ESR1 within the RP3V are critical for the generation of the LH surge and estrous cyclicity in the mouse.

scholarly journals Interactions between neurotensin and GnRH neurons in the positive feedback control of GnRH/LH secretion in the mouse

2010 ◽  
Vol 298 (1) ◽  
pp. E80-E88 ◽  
Author(s):  
Heather M. Dungan Lemko ◽  
Roxana Naderi ◽  
Valeriya Adjan ◽  
Lothar H. Jennes ◽  
Victor M. Navarro ◽  
...  
Keyword(s):  
Basal Forebrain ◽  
Neural Circuits ◽  
Direct Role ◽  
Lh Surge ◽  
Periventricular Nucleus ◽  
Gnrh Neurons ◽  
Gnrh Release ◽  
Double Label ◽  
Lh Secretion

In female mammals, increased ovarian estradiol (E2) secretion triggers GnRH release from neurons in the basal forebrain, which drives LH secretion from the pituitary and subsequently induces ovulation. However, the neural circuits that activate this preovulatory GnRH/LH surge remain unidentified. Neurotensin is expressed in neurons of the anteroventral periventricular nucleus (AVPV), a region thought to be critical for generating the preovulatory GnRH/LH surge. E2 induces neurotensin ( Nts) gene expression in this region, and blockade of neurotensin signaling reduces the LH surge in the rat. We postulated that neurotensin signaling plays a similar role in generating the E2-induced GnRH/LH surge in mice. We used in situ hybridization (ISH) to determine whether E2 induces Nts expression in the mouse and found evidence to support this proposition. Next, we determined that the neurotensin receptor (Ntsr2) is present in many GnRH-expressing neurons. Since the kisspeptin gene ( Kiss1) is expressed in the AVPV and is responsive to E2, we predicted that some neurons in this region express both Kiss1 and Nts; however, by double-label ISH, we observed no coexpression of the two mRNAs. We also postulated that Nts mRNA expression would increase in parallel with the E2-induced LH surge and that the central (icv) administration of neurotensin would stimulate LH secretion and activation of GnRH neurons but found no evidence to support either of these hypotheses. Together, these findings suggest that, although neurotensin neurons in the AVPV are targets for regulation by E2, neurotensin does not appear to play a direct role in generating the GnRH/LH surge in the mouse.

scholarly journals Evidence for a Putative Circadian Kiss-Clock in the Hypothalamic AVPV in Female Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (8) ◽  
pp. 2999-3011 ◽  
Author(s):  
David Chassard ◽  
Isabelle Bur ◽  
Vincent-Joseph Poirel ◽  
Jorge Mendoza ◽  
Valérie Simonneaux
Keyword(s):  
Circadian Clock ◽  
Time Of Day ◽  
Daily Rhythm ◽  
Circadian Period ◽  
Suprachiasmatic Nuclei ◽  
Intact Female ◽  
Lh Surge ◽  
Female Mice ◽  
Periventricular Nucleus ◽  
Clock Protein

Abstract The kisspeptin (Kp) neurons in the anteroventral periventricular nucleus (AVPV) are essential for the preovulatory LH surge, which is gated by circulating estradiol (E2) and the time of day. We investigated whether AVPV Kp neurons in intact female mice may be the site in which both E2 and daily signals are integrated and whether these neurons may host a circadian oscillator involved in the timed LH surge. In the afternoon of proestrous day, Kp immunoreactivity displayed a marked and transient decrease 2 hours before the LH surge. In contrast, Kp content was stable throughout the day of diestrus, when LH levels are constantly low. AVPV Kp neurons expressed the clock protein period 1 (PER1) with a daily rhythm that is phase delayed compared with the PER1 rhythm measured in the main clock of the suprachiasmatic nuclei (SCN). PER1 rhythm in the AVPV, but not in the SCN, exhibited a significant phase delay of 2.8 hours in diestrus as compared with proestrus. Isolated Kp-expressing AVPV explants from PER2::LUCIFERASE mice displayed sustained circadian oscillations of bioluminescence with a circadian period (23.2 h) significantly shorter than that of SCN explants (24.5 h). Furthermore, in AVPV explants incubated with E2 (10 nM to 1 μM), the circadian period was lengthened by 1 hour, whereas the SCN clock remained unaltered. In conclusion, these findings indicate that AVPV Kp neurons display an E2-dependent daily rhythm, which may possibly be driven by an intrinsic circadian clock acting in combination with the SCN timing signal.

scholarly journals Multitissue Circadian Expression of RatperiodHomolog (rPer2) mRNA Is Governed by the Mammalian Circadian Clock, the Suprachiasmatic Nucleus in the Brain

1998 ◽  
Vol 273 (42) ◽  
pp. 27039-27042 ◽  
Author(s):  
Katsuhiko Sakamoto ◽  
Takahiro Nagase ◽  
Hiromi Fukui ◽  
Kazumasa Horikawa ◽  
Tetsuya Okada ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Circadian Expression ◽  
The Brain

scholarly journals Global But Not Gonadotrope-Specific Disruption of Bmal1 Abolishes the Luteinizing Hormone Surge Without Affecting Ovulation

Endocrinology ◽  
2013 ◽  
Vol 154 (8) ◽  
pp. 2924-2935 ◽  
Author(s):  
Adrienne Chu ◽  
Lei Zhu ◽  
Ian D. Blum ◽  
Oliver Mai ◽  
Alexei Leliavski ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Circadian Clock ◽  
Estrous Cycle ◽  
Suprachiasmatic Nucleus ◽  
Cycle Length ◽  
Constant Darkness ◽  
Circadian Regulation ◽  
Lh Surge ◽  
Luteinizing Hormone Surge

Abstract Although there is evidence for a circadian regulation of the preovulatory LH surge, the contributions of individual tissue clocks to this process remain unclear. We studied female mice deficient in the Bmal1 gene (Bmal1−/−), which is essential for circadian clock function, and found that they lack the proestrous LH surge. However, spontaneous ovulation on the day of estrus was unaffected in these animals. Bmal1−/− females were also deficient in the proestrous FSH surge, which, like the LH surge, is GnRH-dependent. In the absence of circadian or external timing cues, Bmal1−/− females continued to cycle in constant darkness albeit with increased cycle length and time spent in estrus. Because pituitary gonadotropes are the source of circulating LH and FSH, we assessed hypophyseal circadian clock function and found that female pituitaries rhythmically express clock components throughout all cycle stages. To determine the role of the gonadotrope clock in the preovulatory LH and FSH surge process, we generated mice that specifically lack BMAL1 in gonadotropes (GBmal1KO). GBmal1KO females exhibited a modest elevation in both proestrous and baseline LH levels across all estrous stages. BMAL1 elimination from gonadotropes also led to increased variability in estrous cycle length, yet GBmal1KO animals were otherwise reproductively normal. Together our data suggest that the intrinsic clock in gonadotropes is dispensable for LH surge regulation but contributes to estrous cycle robustness. Thus, clocks in the suprachiasmatic nucleus or elsewhere must be involved in the generation of the LH surge, which, surprisingly, is not required for spontaneous ovulation.

scholarly journals Circadian expression of 86- and 84-kDa heat shock proteins in the mouse suprachiasmatic nucleus

2008 ◽  
Vol 29 (2) ◽  
pp. 93-98 ◽  
Author(s):  
Tsuyoshi FUKUYAMA ◽  
Masao DOI ◽  
Masahiro MATSUO ◽  
Hiromi NISHINAGA ◽  
Shigeru MIYAKE ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Suprachiasmatic Nucleus ◽  
Circadian Expression ◽  
Shock Proteins

Ras Activity Oscillates in the Mouse Suprachiasmatic Nucleus and Modulates Circadian Clock Dynamics

2015 ◽  
Vol 53 (3) ◽  
pp. 1843-1855 ◽  
Author(s):  
Tsvetan Serchov ◽  
Antje Jilg ◽  
Christian T. Wolf ◽  
Ina Radtke ◽  
Jörg H. Stehle ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Suprachiasmatic Nucleus
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