scholarly journals Rethinking progesterone regulation of female reproductive cyclicity

2016 ◽  
Vol 113 (15) ◽  
pp. 4212-4217 ◽  
Author(s):  
Kaiyu Kubota ◽  
Wei Cui ◽  
Pramod Dhakal ◽  
Michael W. Wolfe ◽  
M. A. Karim Rumi ◽  
...  
Keyword(s):  
Wheel Running ◽  
Hormonal Control ◽  
Female Rats ◽  
Null Mutation ◽  
Wild Type ◽  
Estrous Cycles ◽  
Genetic Ablation ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Cyclic Changes

The progesterone receptor (PGR) is a ligand-activated transcription factor with key roles in the regulation of female fertility. Much has been learned of the actions of PGR signaling through the use of pharmacologic inhibitors and genetic manipulation, using mouse mutagenesis. Characterization of rats with a null mutation at the Pgr locus has forced a reexamination of the role of progesterone in the regulation of the female reproductive cycle. We generated two Pgr mutant rat models, using genome editing. In both cases, deletions yielded a null mutation resulting from a nonsense frame-shift and the emergence of a stop codon. Similar to Pgr null mice, Pgr null rats were infertile because of deficits in sexual behavior, ovulation, and uterine endometrial differentiation. However, in contrast to the reported phenotype of female mice with disruptions in Pgr signaling, Pgr null female rats exhibit robust estrous cycles. Cyclic changes in vaginal cytology, uterine histology, serum hormone levels, and wheel running activity were evident in Pgr null female rats, similar to wild-type controls. Furthermore, exogenous progesterone treatment inhibited estrous cycles in wild-type female rats but not in Pgr-null female rats. As previously reported, pharmacologic antagonism supports a role for PGR signaling in the regulation of the ovulatory gonadotropin surge, a result at variance with experimentation using genetic ablation of PGR signaling. To conclude, our findings in the Pgr null rat challenge current assumptions and prompt a reevaluation of the hormonal control of reproductive cyclicity.

The ‘suprachiasmatic syndrome’: endocrine and behavioural abnormalities following lesions of the suprachiasmatic nuclei in the female rat

1977 ◽  
Vol 198 (1132) ◽  
pp. 297-314 ◽  
Keyword(s):  
Wheel Running ◽  
Plasma Corticosterone ◽  
Female Rats ◽  
Transferase Activity ◽  
Female Rat ◽  
Suprachiasmatic Nuclei ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Pineal Serotonin ◽  
Response To Stress

Lesions of the suprachiasmatic nuclei that caused failure of spontaneous ovulation in female rats consistently produced abnormalities in other functions that are normally influenced by the light-dark cycle. In such animals morning plasma corticosterone concentrations were abnormally high and evening values abnormally low though the response to stress was unaffected. Pineal serotonin N -acetyl transferase activity was abnormally high in animals killed during the day and abnormally low in those killed at night. Although the animals were in persistent be­havioural oestrus, total voluntary wheel-running activity was not con­sistently altered but was distributed evenly between the light and dark periods rather than being confined principally to the dark periods as in normal animals. Similarly the proportion of the daily water and food intake that occurred during the dark period was reduced. The incidence of these associated abnormalities was low in lesioned rats that continued to ovulate spontaneously.

scholarly journals Altered circadian activity and sleep/wake rhythms in the stable tubule only polypeptide (STOP) null mouse model of schizophrenia

SLEEP ◽  
2020 ◽  
Author(s):  
Samuel Deurveilher ◽  
Kristin Robin Ko ◽  
Brock St C Saumure ◽  
George S Robertson ◽  
Benjamin Rusak ◽  
...  
Keyword(s):  
Wheel Running ◽  
Active Phase ◽  
Null Mouse ◽  
Wild Type ◽  
Activity Rhythms ◽  
Lighting Conditions ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Lower Amplitude ◽  
Free Running

Abstract Sleep and circadian rhythm disruptions commonly occur in individuals with schizophrenia. Stable tubule only polypeptide (STOP) knockout (KO) mice show behavioral impairments resembling symptoms of schizophrenia. We previously reported that STOP KO mice slept less and had more fragmented sleep and waking than wild-type littermates under a light/dark (LD) cycle. Here, we assessed the circadian phenotype of male STOP KO mice by examining wheel-running activity rhythms and EEG/EMG-defined sleep/wake states under both LD and constant darkness (DD) conditions. Wheel-running activity rhythms in KO and wild-type mice were similarly entrained in LD, and had similar free-running periods in DD. The phase delay shift in response to a light pulse given early in the active phase under DD was preserved in KO mice. KO mice had markedly lower activity levels, lower amplitude activity rhythms, less stable activity onsets, and more fragmented activity than wild-type mice in both lighting conditions. KO mice also spent more time awake and less time in rapid eye movement sleep (REMS) and non-REMS (NREMS) in both LD and DD conditions, with the decrease in NREMS concentrated in the active phase. KO mice also showed altered EEG features and higher amplitude rhythms in wake and NREMS (but not REMS) amounts in both lighting conditions, with a longer free-running period in DD, compared to wild-type mice. These results indicate that the STOP null mutation in mice altered the regulation of sleep/wake physiology and activity rhythm expression, but did not grossly disrupt circadian mechanisms.

Melatonin and activity rhythm responses to light pulses in mice with the Clock mutation

2003 ◽  
Vol 284 (5) ◽  
pp. R1231-R1240 ◽  
Author(s):  
David J. Kennaway ◽  
Athena Voultsios ◽  
Tamara J. Varcoe ◽  
Robert W. Moyer
Keyword(s):  
Wheel Running ◽  
Activity Rhythm ◽  
Mutant Mice ◽  
Constant Darkness ◽  
Wild Type ◽  
Continuous Darkness ◽  
Light Pulses ◽  
Essentially Normal ◽  
Running Activity ◽  
Wheel Running Activity

Melatonin and wheel-running rhythmicity and the effects of acute and chronic light pulses on these rhythms were studied in Clock Δ19 mutant mice selectively bred to synthesize melatonin. Homozygous melatonin-proficient Clock Δ19 mutant mice ( Clock Δ19/Δ19 -MEL) produced melatonin rhythmically, with peak production 2 h later than the wild-type controls (i.e., just before lights on). By contrast, the time of onset of wheel-running activity occurred within a 20-min period around lights off, irrespective of the genotype. Melatonin production in the mutants spontaneously decreased within 1 h of the expected time of lights on. On placement of the mice in continuous darkness, the melatonin rhythm persisted, and the peak occurred 2 h later in each cycle over the first two cycles, consistent with the endogenous period of the mutant. This contrasted with the onset of wheel-running activity, which did not shift for several days in constant darkness. A light pulse around the time of expected lights on followed by constant darkness reduced the expected 2-h delay of the melatonin peak of the mutants to ∼1 h and advanced the time of the melatonin peak in the wild-type mice. When the Clock Δ19/Δ19 -MEL mice were maintained in a skeleton photoperiod of daily 15-min light pulses, a higher proportion entrained to the schedule (57%) than melatonin-deficient mutants (9%). These results provide compelling evidence that mice with the Clock Δ19 mutation express essentially normal rhythmicity, albeit with an underlying endogenous period of 26–27 h, and they can be entrained by brief exposure to light. They also raise important questions about the role of Clock in rhythmicity and the usefulness of monitoring behavioral rhythms compared with hormonal rhythms.

Introduction Of A High-fat/sucrose Diet Modulates Voluntary Wheel Running Activity In Adult Female Rats

2017 ◽  
Vol 49 (5S) ◽  
pp. 440
Author(s):  
Jon-Philippe K. Hyatt ◽  
Lindsay Caprio ◽  
Elisa J. Bienenstock ◽  
Jung A. Kim ◽  
Gary E. McCall
Keyword(s):  
Adult Female ◽  
Wheel Running ◽  
Female Rats ◽  
High Fat ◽  
Voluntary Wheel Running ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Sucrose Diet ◽  
Voluntary Wheel

Metabolic rhythm abnormalities in mice lacking VIP-VPAC2 signaling

2008 ◽  
Vol 294 (2) ◽  
pp. R344-R351 ◽  
Author(s):  
David A. Bechtold ◽  
Timothy M. Brown ◽  
Simon M. Luckman ◽  
Hugh D. Piggins
Keyword(s):  
Knockout Mice ◽  
Wheel Running ◽  
Neuronal Firing ◽  
Receptor Expression ◽  
Wild Type ◽  
Lighting Condition ◽  
Temporal Regulation ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Feeding Rhythms

The circadian pacemaker in the suprachiasmatic nuclei (SCN) controls endogenous near 24-h physiological and behavioral rhythms in metabolism, neuroendocrine function, and locomotor activity. Recently, we showed that vasoactive intestinal polypeptide (VIP) and its receptor, VPAC2 are critical to the intercellular communication between individual SCN neurons, and appropriate synchronization and phasing of these oscillatory cells. Mice defective in VIP signaling manifest grossly impaired circadian rhythms of SCN neuronal firing activity and are typically unable to maintain rhythmic wheel-running behavior in the absence of external time cues. Here we report that daily rhythms of metabolism and feeding behavior are also overtly altered in these animals. Under diurnal conditions (12:12-h light-dark; LD), metabolic and feeding rhythms are advanced in mice lacking either VIP or VPAC2 receptor expression, peaking in the late day, rather than early night, as observed in wild-type mice. When placed in constant light (LL), both VIP-deficient and VPAC2 receptor-knockout mice exhibit dampening of metabolic and feeding rhythms, which deteriorate after a few days. In addition, overall metabolic rate is greatly reduced in VPAC2-knockout mice, when compared with wild-type mice, regardless of lighting condition. The advancement of metabolic and feeding rhythms in these mice under LD suggests that these rhythms are less sensitive to masking by light. These results demonstrate that altering SCN function not only affects neuronal and wheel-running activity rhythms but also dramatically impairs temporal regulation of metabolism and feeding.

scholarly journals SUN-265 Reduced Locomotive Behaviour and Increased Arcuate Nucleus Inflammation Are Observed in KISS1R KO Male Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Raj Patel ◽  
Shane K Maloney ◽  
Jeremy Troy Smith
Keyword(s):  
Arcuate Nucleus ◽  
Wheel Running ◽  
Free Access ◽  
Wild Type ◽  
Voluntary Activity ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Significant Difference ◽  
Hypothalamic Inflammation ◽  
Running Wheels

Abstract The neuropeptide kisspeptin, encoded by the Kiss1 gene, binds the G- protein-coupled receptor Kiss1r (also known as GPR54) and is a novel player in the delicate balance of energy intake and expenditure. Mice that have a dysfunctional gene for Kiss1r develop an obese and diabetic phenotype. To further study how kisspeptin signalling impacts on energy balance, we investigated the relationship between absent kisspeptin signalling and locomotor behaviour in Kiss1rKO and wild type mice. Mice had free access to running wheels, and we examined the characteristics of wheel running over three weeks, and its flow-on effects on body mass. We subsequently examined dopaminergic neurons (via tyrosine hydroxylase (TH) staining) and hypothalamic inflammation (via Iba1 stained microglia). These studies also were performed following gonadectomy (GDX), to control for gonadal steroids. In intact males, the knockout (KO) mice covered only 10% of the distance travelled by wild-type (WT) per 24h (WT, 6363±643m; KO, 652±219m; P<0.0001). Moreover, in the WT there was a clear circadian pattern to the wheel-running activity, with most activity during lights off, while in the KO the running appeared randomly distributed across the 24h. After GDX, KO males continued to run significantly less than their WT counterparts (WT, 1652±474m; KO, 998±219m). In intact females, the KO mice covered only 23% of the distance travelled by WT per 24h (WT, 6030±747m; KO, 1379±364m; P<0.004). In OVX females, there was no difference between WT and KO mice (WT, 4150±1367m; KO, 3117±830m). Bodyweight analysis showed that access to running wheels prevented obesity usually seen in the Kiss1rKO mouse. In fact, in GDX males and females (at days 21 and 22 of wheel running) the KO mice were significantly lighter than WTs (at day 22: males, WT 28.67g; KO, 23.70g; P<0.05; females, WT, 27.38g; KO, 23.30g; P<0.05). Examination of TH revealed no significant difference in expression in the different genotypes in both sexes, in all areas examined. Investigation of Iba1 revealed significant higher counts in the male KO compared to the WT in the arcuate nucleus, but no difference in any other regions. We show that the locomotor activity in male and female Kiss1r KO mice is heavily dependent on the status of gonadal sex steroids. However, the lower running activity in male KO compared to WT remained after GDX, and this was paired with an elevated inflammation marker in the arcuate nucleus. Whether absent kisspeptin signalling acts as a significant regulator of voluntary activity is debatable, but patterns of locomotion behaviour could be disrupted, potentially involving circadian rhythm, this is under further investigation.

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