scholarly journals Abnormal Response of the Neuropeptide Y-Deficient Mouse Reproductive Axis to Food Deprivation But Not Lactation

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 1780-1786 ◽  
Author(s):  
Jennifer W. Hill ◽  
Jon E. Levine
Keyword(s):  
Neuropeptide Y ◽  
Food Consumption ◽  
Food Deprivation ◽  
Normal Female ◽  
Estrous Cycles ◽  
Energy Deficiency ◽  
Steroid Dependent ◽  
Reproductive Axis ◽  
Estrous Cyclicity ◽  
Lh Release

Neuropeptide Y (NPY) plays a key role in both food intake and GnRH secretion. Food deprivation elevates hypothalamic NPY activity and suppresses LH and gonadal steroid secretion. Similarly, lactation up-regulates NPY expression as food consumption increases and estrous cycles cease. These observations suggest that NPY coordinates reproductive suppression in response to energy deficiency; if so, the reproductive axis of NPY knockout (KO) mice should be impervious to lactation and food deprivation. We monitored food consumption, body weight, and estrous cyclicity during lactation in NPY KO mice with large and small litters. NPY KO mice with either litter size resembled wild types (WTs) in weight regulation and food consumption. Large-litter mothers had longer anestrous periods and smaller pups at weaning, but NPY KOs and WTs did not differ in either respect. We also examined the LH response of NPY KO mice to 48 h without food. Basal levels of LH in ovariectomized NPY KO animals decreased in response to fasting, but LH levels in intact and estrogen-treated ovariectomized NPY KO animals did not. In contrast, WTs consistently showed fasting-induced suppression of LH. Our findings suggest that other systems can sustain the hyperphagia of lactation and NPY alone is not responsible for suppressing cyclicity during lactation. Nevertheless, the suppression of basal LH release that accompanies food deprivation in normal female mice appears to require the steroid-dependent actions of NPY.

scholarly journals Deficiency of Arcuate Nucleus Kisspeptin Results in Post-Pubertal Central Hypogonadism

2021 ◽  
Author(s):  
Nimisha Nandankar ◽  
Ariel L. Negron ◽  
Andrew Wolfe ◽  
Jon E Levine ◽  
Sally Radovick
Keyword(s):  
Feedback Control ◽  
Arcuate Nucleus ◽  
Critical Role ◽  
Knock Out ◽  
Protein Levels ◽  
Reproductive Axis ◽  
Lh Pulsatility ◽  
Estrous Cyclicity ◽  
Lh Release ◽  
Kndy Neurons

Kisspeptin (encoded by Kiss1), a neuropeptide critically involved in neuroendocrine regulation of reproduction, is primarily synthesized in two hypothalamic nuclei: the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). AVPV kisspeptin is thought to regulate the estrogen-induced positive feedback control of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH), and the pre-ovulatory LH surge in females. In contrast, ARC kisspeptin neurons, which largely co-express neurokinin B and dynorphin A (collectively named KNDy neurons), are thought to mediate estrogen-induced negative feedback control of GnRH/LH and be the major regulators of pulsatile GnRH/LH release. However, definitive data to delineate the specific roles of AVPV versus ARC kisspeptin neurons in the control of GnRH/LH release is lacking. Therefore, we generated a novel mouse model targeting deletion of Kiss1 to the ARC nucleus (Pdyn-Cre/Kiss1fl/fl KO) to determine the functional differences between ARC and AVPV kisspeptin neurons on the reproductive axis. The efficacy of the knock-out was confirmed at both the mRNA and protein levels. Adult female Pdyn-Cre/Kiss1fl/fl KO mice exhibited persistent diestrus and significantly fewer LH pulses when compared to controls, resulting in arrested folliculogenesis, hypogonadism, and infertility. Pdyn-Cre/Kiss1fl/fl KO males also exhibited disrupted LH pulsatility, hypogonadism, and variable, defective spermatogenesis and subfertility. The timing of pubertal onset in males and females was equivalent to controls. These findings add to the current body of evidence for the critical role of kisspeptin in ARC KNDy neurons in GnRH/LH pulsatility in both sexes, while directly establishing ARC kisspeptin's role in regulating estrous cyclicity in female mice, and gametogenesis in both sexes, and culminating in disrupted fertility. The Pdyn-Cre/Kiss1fl/fl KO mice present a novel mammalian model of post-pubertal central hypogonadism.

scholarly journals An Antagonistic Peptide of Gpr1 Ameliorates LPS-Induced Depression through the Hypothalamic-Pituitary-Ovarian Axis

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 857
Author(s):  
Rongrong Li ◽  
Chiyuan Ma ◽  
Yue Xiong ◽  
Huashan Zhao ◽  
Yali Yang ◽  
...  
Keyword(s):  
Ovarian Function ◽  
Preference Test ◽  
Antidepressant Effect ◽  
Normal Female ◽  
Reproductive Axis ◽  
Immobility Time ◽  
Potential Therapeutic Application ◽  
Antagonistic Peptide ◽  
Sucrose Preference Test ◽  
G Protein Coupled

Depression affects the reproductive axis at the hypothalamus and pituitary levels, which has a significant impact on female fertility. It has been reported that G protein-coupled receptor 1 (Gpr1) mRNA is expressed in both the hypothalamus and ovaries. However, it is unclear whether there is a relationship between Gpr1 and depression, and its role in ovarian function is unknown. Here, the expression of Gpr1 was recorded in the hypothalamus of normal female mice, and co-localized with gonadotrophin-releasing hormone (GnRH) and corticotropin-releasing factor (CRF). We established a depression mouse model to evaluate the antidepressant effect of G5, an antagonistic peptide of Gpr1. The results show that an intraperitoneal injection of G5 improves depressant–like behaviors remarkably, including increased sucrose intake in the sucrose preference test and decreased immobility time in the forced swimming tests. Moreover, G5 treatment increased the release of reproductive hormone and the expression of ovarian gene caused by depression. Together, our findings reveal a link between depression and reproductive diseases through Gpr1 signaling, and suggest antagonistic peptide of Gpr1 as a potential therapeutic application for hormone-modulated depression in women.

Possible role of serotonin and neuropeptide Y on the disruption of the reproductive axis activity by perfluorooctane sulfonate

2015 ◽  
Vol 233 (2) ◽  
pp. 138-147 ◽  
Author(s):  
S. López-Doval ◽  
R. Salgado ◽  
B. Fernández-Pérez ◽  
A. Lafuente
Keyword(s):  
Neuropeptide Y ◽  
Perfluorooctane Sulfonate ◽  
Reproductive Axis

Female Hyperandrogenism in Elite Sports and the Athletic Triad

2021 ◽  
Author(s):  
Angelica Lindén Hirschberg
Keyword(s):  
Female Athletes ◽  
Polycystic Ovary ◽  
Disorders Of Sex Development ◽  
Normal Female ◽  
Menstrual Disorders ◽  
Mineral Density ◽  
Energy Deficiency ◽  
Sex Development ◽  
Endocrine Disturbances ◽  
Increased Risk

AbstractEssential hyperandrogenism seems to be overrepresented in female elite athletes. This applies to mild forms such as polycystic ovary syndrome, as well as rare differences/disorders of sex development (DSD). The reason is likely a selection bias since there is increasing evidence that androgens are beneficial for athletic performance by potent anabolic effects on muscle mass and bone mass, and stimulation of erythropoiesis. XY DSD may cause a greatly increased production of testosterone in the male range, that is, 10 to 20 times higher than the normal female range. The established regulations concerning the eligibility of female athletes with severe hyperandrogenism to compete in the female classification remain controversial. The most common cause of menstrual disorders in female athletes, however, is probably an acquired functional hypothalamic disturbance due to energy deficiency in relation to energy expenditure, which could lead to low bone mineral density and increased risk of injury. This condition is particularly common in endurance and esthetic sports, where a lean body composition is considered an advantage for physical performance. It is important to carefully evaluate endocrine disturbances and menstrual disorders in athletes since the management should be specific according to the underlying cause.

Interactive effects of food deprivation and exercise on reproductive function in female hamsters

1994 ◽  
Vol 267 (1) ◽  
pp. R185-R190 ◽  
Author(s):  
J. B. Powers ◽  
A. E. Jetton ◽  
G. N. Wade
Keyword(s):  
Food Deprivation ◽  
Reproductive Function ◽  
Hormonal Treatment ◽  
Estradiol Benzoate ◽  
Interactive Effects ◽  
Combined Effects ◽  
Inhibitory Effects ◽  
Estrous Cycles ◽  
Running Wheels ◽  
Estrous Behavior

Two experiments evaluated the combined effects of food deprivation and runningwheel access on estrous cycles and estrous behavior of female hamsters. In experiment 1, food deprivation on days 1 and 2 of the estrous cycle disrupted the next expected ovulation, and this effect was more, rather than less, robust in females allowed to exercise in running wheels while they were deprived. In experiment 2, a similar protocol was used except the females were ovariectomized and received sequential injections of estradiol benzoate (EB; 5 micrograms) and progesterone (P; 200 micrograms) separated by 48 h to induce lordosis, which was tested 4-5 after P. Food deprivation concomitant with hormonal treatment diminished lordosis durations, but this effect was significant only among the females that were permitted to run in activity wheels. Previous findings demonstrated that access to running wheels attenuated the inhibitory effects of short photoperiod exposure on hamster estrous cycles. In contrast, the present results indicate that this same manipulation exaggerates rather than diminishes the inhibitory effects of food deprivation on estrous cycles and hormone-induced behavioral estrus.

scholarly journals Upregulation of Kiss-1 and Gpr54 Genes Expression in Pituitary of Male Rats Following the Central Administration of Neuropeptide Y

2019 ◽  
Vol 4 (4) ◽  
pp. 137-142
Author(s):  
Vahid Azizi ◽  
Shahrbanoo Oryan ◽  
Homayuon Khazali ◽  
Abdolkarim Hosseini
Keyword(s):  
Gene Expression ◽  
Pituitary Gland ◽  
Neuropeptide Y ◽  
Wistar Rats ◽  
Third Ventricle ◽  
Male Rats ◽  
Control Group ◽  
Central Administration ◽  
Reproductive Axis ◽  
Male Wistar Rats

Introduction: The neuropeptide Y (NPY) in the neural circuits of the hypothalamus has a stimulating effect on reproductive activities in mammals. Kisspeptin (KiSS1) is a quintessential neurotransmitter in the reproductive axis which directly stimulates gonadotropin-releasing hormone neurons in the hypothalamus. The distribution of KiSS1 expressing cells in the pituitary was described previously. Despite earlier reports showing the KiSS1 receptor, G-protein coupled receptor 54 (GPR54) expression in the pituitary, the potential physiological roles of kisspeptin at this gland have remained obscure. Accordingly, this study investigated the role of NPY on the relative expression of Kiss1 and Gpr54 genes in the pituitary gland in male Wistar rats. Methods: In general, 20 male Wistar rats weighing 200-250 g in 4 groups (5 in each group) received saline, NPY (2.3 nM), BIBP3226 (NPY receptor antagonist, 7.8 nM), and NPY+ BIBP3226. Then, they received the simultaneous injection of these molecules through the third ventricle of the brain. Finally, the relative mean expressions of Kiss1 and Gpr54 genes in the anterior pituitary were quantitatively analyzed by the real-time polymerase chain reaction. Results: The central injection of NPY increased the relative mean expressions of Kiss1 and Gpr54 genes in the pituitary gland compared to the control group although the injection of BIBP3226 eradicated these effects. However, the gene expression of Gpr54 in the rats receiving NPY coupled with BIBP3226 in hypophysis in comparison to the group receiving only NPY demonstrated a significant reduction (P<0.05). Conclusion: Overall, the central injection of NPY stimulated the gene expression of Kiss1 and Gpr54 in the pituitary gland.

Effects of the fructose analog, 2,5-anhydro-D-mannitol, on food intake and estrous cyclicity in Syrian hamsters

1997 ◽  
Vol 272 (3) ◽  
pp. R935-R939
Author(s):  
J. E. Schneider
Keyword(s):  
Food Intake ◽  
Plasma Glucose ◽  
Acid Oxidation ◽  
Estrous Cycles ◽  
Syrian Hamsters ◽  
Glucose Levels ◽  
Fuel Metabolism ◽  
Increase Food Intake ◽  
Estrous Cyclicity ◽  
Estrous Cycling

Hyperphagia and anovulation are both triggered by prior food deprivation or other treatments that decrease intracellular availability of metabolic fuels in most species studied. Syrian hamsters fail to show compensatory hyperphagia, but do show anestrus in response to these energetic challenges. In the present experiments, we examined food intake, plasma glucose levels, and estrous cyclicity in Syrian hamsters in response to 2,5-anhydro-D-mannitol (2,5-AM), a fructose analog that is thought to trigger eating in rats by depleting intracellular levels of ATP. In experiment 1, female estrous cycling hamsters were treated with 100, 200, 400, or 800 mg/kg 2,5-AM or the vehicle by intraperitoneal injection. Food intake was measured 1, 2, 4, 8, and 24 h after treatment. There were no statistically significant increases in food intake in response to any dose of 2,5-AM. In experiment 2, blood samples were drawn at 0, 1, 3, 5, 7, and 25 h after hamsters were treated with 0 or 400 mg/kg 2,5-AM. 2,5-AM treatment resulted in a mild but significant decrease in plasma glucose levels similar to those seen in 2,5-AM-treated rats, suggesting that 2,5-AM has similar effects on fuel metabolism in rats and hamsters. In experiment 3, hamsters received 2,5-AM, 2,5-AM plus the fatty acid oxidation inhibitor methyl palmoxirate, or vehicle every 6 h over the first 48 h of the estrous cycle and were tested for indexes of estrous cyclicity at the end of the cycle. All hamsters showed normal estrous cycles, regardless of treatment. If 2,5-AM has similar metabolic consequences in rats and hamsters, the present results suggest that decreased intracellular levels of ATP and mild hypoglycemia do not increase food intake or inhibit estrous cyclicity in Syrian hamsters.

Effect of difluoromethylornithine on the LH surge and subsequent ovulation in the rat

1988 ◽  
Vol 117 (3) ◽  
pp. 447-453 ◽  
Author(s):  
S. A. Nicholson ◽  
M. Aslam ◽  
T. T. Chuang ◽  
B. Gillham ◽  
M. T. Jones
Keyword(s):  
Ornithine Decarboxylase ◽  
Plasma Concentrations ◽  
Specific Inhibitor ◽  
Steroid Production ◽  
Lh Surge ◽  
Direct Observations ◽  
Steroid Dependent ◽  
Lh Release ◽  
Plasma Oestradiol

ABSTRACT Female Wistar-derived rats with regular oestrous cycles were injected s.c. at 15.00 h on pro-oestrus with difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase. The drug (10–100 mg/rat) caused a dose-related reduction in the concentration of LH in plasma taken at 19.00 h (the time of the peak of the LH surge in this colony). There was also a dose-related reduction in the pituitary content of total polyamines. The reduction in the plasma concentration of LH was not due to the shifting of the time of the peak of the surge, as concentrations were significantly lower than control from 17.00 to 21.00 h, the overall reduction in total LH release being approximately 50%. The number of ova in the oviducts at 06.00 h next morning was significantly reduced by treatment with 50 mg DFMO/rat, by an average of 70%. Injection of DFMO enhanced the fall in plasma oestradiol concentrations seen between 15.00 and 19.00 h, in a dose-related manner. It also prevented the rise in progesterone concentrations seen in control animals during this period. The ability of DFMO to prevent the rise in plasma concentrations of LH was not secondary to the effects of the drug on ovarian steroid production because DFMO also significantly reduced the LH surge in animals ovariectomized on dioestrus and given appropriate replacement injections of oestradiol and progesterone. It seems possible that part of the action of DFMO is exercised at the hypothalamus, since when 50 mg DFMO/rat was given either 2 or 4 h before the expected peak of the LH surge, the LHRH content of the hypothalamus was significantly reduced at that time. These results suggest that activation of ornithine decarboxylase is a necessary prerequisite for a normal LH surge, and that this activation is steroid-dependent. This conclusion is borne out by results from direct observations on the activity of the enzyme in pituitary tissue incubated in vitro. J. Endocr. (1988) 117, 447–453

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