scholarly journals Undernutrition reduces kisspeptin and neurokinin B expression in castrated male sheep

2020 ◽  
Vol 1 (1) ◽  
pp. 21-33
Author(s):  
Christina M Merkley ◽  
Allison N Renwick ◽  
Sydney L Shuping ◽  
KaLynn Harlow ◽  
Jeffrey R Sommer ◽  
...  
Keyword(s):  
Body Weight ◽  
Luteinizing Hormone ◽  
Hormone Secretion ◽  
Reproductive Function ◽  
Feed Restriction ◽  
Neurokinin B ◽  
Lh Secretion ◽  
The Brain ◽  
Male Sheep

Undernutrition impairs reproductive success through suppression of gonadotropin-releasing hormone (GnRH), and subsequently luteinizing hormone (LH), secretion. Given that kisspeptin and neurokinin B (NKB) neurons in the arcuate nucleus (ARC) of the hypothalamus are thought to play key stimulatory roles in the generation of GnRH/LH pulses, we hypothesized that feed restriction would reduce the ARC mRNA abundance and protein expression of kisspeptin and NKB in young, male sheep. Fourteen wethers (castrated male sheep five months of age) were either fed to maintain (FM; n = 6) pre-study body weight or feed-restricted (FR; n = 8) to lose 20% of pre-study body weight over 13 weeks. Throughout the study, weekly blood samples were collected and assessed for LH concentration using RIA. At Week 13 of the experiment, animals were killed, heads were perfused with 4% paraformaldehyde, and brain tissue containing the hypothalamus was collected, sectioned, and processed for detection of mRNA (RNAscope) and protein (immunohistochemistry) for kisspeptin and NKB. Mean LH was significantly lower and LH inter-pulse interval was significantly higher in FR wethers compared to FM wethers at the end of the experiment (Week 13). RNAscope analysis revealed significantly fewer cells expressing mRNA for kisspeptin and NKB in FR wethers compared to FM controls, and immunohistochemical analysis revealed significantly fewer immunopositive kisspeptin and NKB cells in FR wethers compared to FM wethers. Taken together, this data supports the idea that long-term feed restriction regulates GnRH/LH secretion through central suppression of kisspeptin and NKB in male sheep. Lay summary While undernutrition is known to impair reproduction at the level of the brain, the components responsible for this in the brain remain to be fully understood. Using male sheep we examined the effect of undernutrition on two stimulatory molecules in the brain critical for reproduction: kisspeptin and neurokinin B. Feed restriction for several weeks resulted in decreased luteinizing hormone in the blood indicating reproductive function was suppressed. In addition, undernutrition also reduced both kisspeptin and neurokinin B levels within a region of the brain involved in reproduction, the hypothalamus. Given that they have stimulatory roles in reproduction, we believe that undernutrition acts in the brain to reduce kisspeptin and neurokinin B levels leading to the reduction in luteinizing hormone secretion. In summary, long-term undernutrition inhibits reproductive function in sheep through suppression of kisspeptin and neurokinin B within the brain.

scholarly journals SAT-LB56 Undernutrition Reduces Transcript Abundance of Kisspeptin and Neurokinin B in Young Male Sheep

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sydney L Shuping ◽  
Allison N Renwick ◽  
Lynn Harlow ◽  
Jeffrey R Sommer ◽  
Christina M Merkley ◽  
...  
Keyword(s):  
Body Weight ◽  
Young Male ◽  
Mrna Abundance ◽  
Nutrient Restriction ◽  
Feed Restriction ◽  
Neurokinin B ◽  
Weight Group ◽  
Body Weights ◽  
Lh Secretion ◽  
Male Sheep

Abstract Proper energy balance is important to ensure reproductive success. Chronic nutrient restriction is known to suppress hypothalamic-pituitary function, but the central mechanisms whereby undernutrition inhibits GnRH/LH secretion remain largely unknown. KNDy neurons, which co-express kisspeptin, neurokinin B (NKB), and dynorphin, form a unique population of cells in the arcuate nucleus (ARC) of the hypothalamus and play a critical role in GnRH/LH pulse generation. Based on recent evidence from our lab that chronic feed restriction reduces kisspeptin and NKB protein expression in young male sheep, we hypothesized that nutrient restriction would inhibit mRNA abundance for kisspeptin and NKB in the same animals. Fourteen wethers were placed into a fed to maintain body weight group (n=6; Fed) or a feed-restricted to lose 15-20% of pre-study body weight group (FR; n=8). Weekly blood samples (every 12 minutes for 4.5 hours) were taken via jugular venipuncture and plasma was stored at -20°C until the time of radioimmunoassay. Weekly body weights were recorded and feed amounts were adjusted to achieve desired body weights. At Week 13, animals were euthanized following blood collection, brain tissue was perfused with 4% paraformaldehyde, and tissue containing the hypothalamus was collected. Following submersion in 20% sucrose for at least four weeks, hypothalamic blocks were sectioned at 50 µm on a freezing microtome, and stored in a cryopreservative solution until processing. At Week 13, the average percent change in body weight was clearly evident (Fed, 6.79 + 3.4% vs FR, -19.82 ± 1.6%), and mean LH was significantly lower in FR wethers (13.41 + 3.7 ng/ml) compared to Fed controls (26.43 + 2.5 ng/ml). To assess changes in mRNA abundance, we used a relatively new in situ hybridization technique, RNAscope, to quantify mRNA for kisspeptin and NKB in the ARC with probes that were ovine-specific. Results showed that feed restriction reduced the number of kisspeptin mRNA-expressing cells (Fed, 231.2 + 14.4 vs FR, 100.3 + 35.9) and NKB mRNA-expressing cells (Fed, 192.7 + 18.4 vs FR, 97.3 + 21.7) per hemi-section. Furthermore, analysis of kisspeptin and NKB co-expressing cells (30 cells/animal) revealed that feed restriction significantly reduced the average mRNA integrated density for NKB, but not kisspeptin, compared to Fed controls. Together, these findings further support a role for kisspeptin and NKB in the central mechanism governing GnRH/LH secretion during undernutrition in male sheep.

Androgenic and oestrogenic steroid participation in feedback control of luteinizing hormone secretion in male sheep

1983 ◽  
Vol 102 (4) ◽  
pp. 499-504 ◽  
Author(s):  
M. J. D'Occhio ◽  
B. D. Schanbacher ◽  
J. E. Kinder
Keyword(s):  
Luteinizing Hormone ◽  
Pulse Generator ◽  
Hormone Secretion ◽  
Pulse Interval ◽  
Serum Concentrations ◽  
Luteinizing Hormone Secretion ◽  
Lh Release ◽  
Lh Secretion ◽  
Additional Feedback ◽  
Male Sheep

Abstract. The acute castrate ram (wether) was used as an experimental model to investigate the site(s) of feedback on luteinizing hormone (LH) by testosterone, dihydrotestosterone and oestradiol. At the time of castration, wethers were implanted subdermally with Silastic capsules containing either crystalline testosterone (three 30 cm capsules), dihydrotestosterone (five 30 cm capsules) or oestradiol (one 6.5 cm capsule). Blood samples were taken at 10 min intervals for 6 h 2 weeks after implantation to determine serum steroid concentrations and to characterize the patterns of LH secretion. Pituitary LH response to exogenous LRH (5 ng/kg body weight) were also determined at the same time. The steroid implants produced serum concentrations of the respective hormones which were either one-third (testosterone) or two-to-four times (dihydrotestosterone, oestradiol) the levels measured in rams at the time of castration. Non-implanted wethers showed rhythmic pulses of LH (pulse interval 40–60 min) and had elevated LH levels (16.1 ± 1.6 ng/ml; mean ± se) 2 weeks after castration. All three steroids suppressed pulsatile LH release and reduced mean LH levels (to below 3 ng/ml) and pituitary LH responses to LRH. Inhibition of pulsatile LH secretion by all three steroids indicated that testosterone as well as its androgenic and oestrogenic metabolites can inhibit the LRH pulse generator in the hypothalamus. Additional feedback on the pituitary was indicated by the dampened LH responses to exogenous LRH.

scholarly journals miR-29a/b1 Regulates the Luteinizing Hormone Secretion and Affects Mouse Ovulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Yang Guo ◽  
Youbing Wu ◽  
Jiahao Shi ◽  
Hua Zhuang ◽  
Lei Ci ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Molecular Mechanisms ◽  
Hormone Secretion ◽  
Reproductive Function ◽  
Mutant Mice ◽  
Vaginal Opening ◽  
Luteinizing Hormone Secretion ◽  
Estrous Cycles ◽  
Female Mice ◽  
Lh Secretion

miR-29a/b1 was reportedly involved in the regulation of the reproductive function in female mice, but the underlying molecular mechanisms are not clear. In this study, female mice lacking miR-29a/b1 showed a delay in vaginal opening, irregular estrous cycles, ovulation disorder and subfertility. The level of luteinizing hormone (LH) was significantly lower in plasma but higher in pituitary of mutant mice. However, egg development was normal in mutant mice and the ovulation disorder could be rescued by the superovulation treatment. These results suggested that the LH secretion was impaired in mutant mice. Further studies showed that deficiency of miR-29a/b1 in mice resulted in an abnormal expression of a number of proteins involved in vesicular transport and exocytosis in the pituitary, indicating the mutant mice had insufficient LH secretion. However, the detailed mechanism needs more research.

Effects of valproate-induced alteration of the GABAergic system on pulsatile luteinizing hormone secretion in ovariectomized women

1996 ◽  
Vol 135 (3) ◽  
pp. 293-298 ◽  
Author(s):  
Joaquin Lado-Abeal ◽  
Jose L Liz ◽  
Carlos Rey ◽  
Manuel Febrero ◽  
Jose Cabezas-Cerrato
Keyword(s):  
Luteinizing Hormone ◽  
Sodium Valproate ◽  
Pulse Generator ◽  
Hormone Secretion ◽  
Gabaergic System ◽  
Luteinizing Hormone Secretion ◽  
Serum Lh ◽  
Nutrition Service ◽  
Significant Difference ◽  
Lh Secretion

Lado-Abeal J, Liz JL, Rey C, Febrero M, Cabezas-Cerrato J. Effects of valproate-induced alteration of the GABAergic system on pulsatile luteinizing hormone secretion in ovariectomized women. Eur J Endocrinol 1996;135:293–8. ISSN 0804–4643 It is well established that valproate increases hypothalamic concentrations of γ-aminobutyric acid (GABA). Although little research has been done on the role of GABA in the control of pulsatile luteinizing hormone (LH) secretion in humans, our group recently found that administration of valproate had no significant effect on pulsatile LH secretion in late follicular and mid-late luteal phase normal women. However, the results of several studies of rats suggest that GABAergic regulation of LH secretion may depend on steroid levels. The objective of this work was to determine whether regular administration of sodium valproate inhibits pulsatile LH secretion in ovariectomized women. Twelve women who had undergone ovariectomy for causes other than malignant tumors were each studied in two 8 h sessions, in each of which blood samples were taken every 5 min. The first session was the control; for the second, 400 mg of sodium valproate was administered every 8 h during the seven preceding days and at 08.00 h and 14.00 h on the day of the study session. Serum valproate was determined by repolarization fluorescence spectrophotometry, and LH, estradiol and progesterone by radioimmunoassay. The serum LH series were subjected to a deconvolution procedure to reconstruct the pattern of pituitary LH secretion. Luteinizing hormone pulses were identified by the authors' nonparametric method. Control and post-valproate results were compared with regard to number of pulses, pulse duration, the quantity of LH secreted in each pulse, interpulse interval and mean serum LH level. There was no statistically significant difference between control and post-valproate results for any of the variables considered. It is concluded that sustained serum valproate levels do not alter pulsatile secretion of LH in ovariectomized women. This implies that, in humans, GABA is probably not a decisive factor in the regulation of the GnRH pulse generator. J Cabezas-Cerrato, Endocrinology and Nutrition Service, General Hospital of Galicia, c/Galeras s/n 15705, Santiago de Compostela, La Coruña, Spain

Effects of alarin on food intake, body weight and luteinizing hormone secretion in male mice

Neuropeptides ◽  
2012 ◽  
Vol 46 (2) ◽  
pp. 99-104 ◽  
Author(s):  
Gregory S. Fraley ◽  
Emily Leathley ◽  
Nicole Lundy ◽  
Emily Chheng ◽  
Issurah King ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Luteinizing Hormone ◽  
Hormone Secretion ◽  
Male Mice ◽  
Luteinizing Hormone Secretion

Leptin Functioning in Eating Disorders

CNS Spectrums ◽  
2004 ◽  
Vol 9 (7) ◽  
pp. 523-529 ◽  
Author(s):  
Palmiero Monteleone ◽  
Antonio DiLieto ◽  
Eloisa Castaldo ◽  
Mario Maj
Keyword(s):  
Physical Activity ◽  
Eating Disorders ◽  
Body Weight ◽  
Eating Behaviors ◽  
Clinical Manifestations ◽  
Immune Functions ◽  
Abnormal Eating ◽  
The Brain

AbstractLeptin is an adipocyte-derived hormone, which is involved predominantly in the long-term regulation of body weight and energy balance by acting as a hunger suppressant signal to the brain. Leptin is also involved in the modulation of reproduction, immune function, physical activity, and some endogenous endocrine axes. Since anorexia nervosa (AN) and bulimia nervosa (BN) are characterized by abnormal eating behaviors, dysregulation of endogenous endocrine axes, alterations of reproductive and immune functions, and increased physical activity, extensive research has been carried out in the last decade in order to ascertain a role of this hormone in the pathophysiology of these syndromes. In this article, we review the available data on leptin physiology in patients with eating disorders. These data support the idea that leptin is not directly involved in the etiology of AN or BN. However, malnutrition-induced alterations in its physiology may contribute to the genesis and/or the maintenance of some clinical manifestations of AN and BN and may have an impact on the prognosis of AN.

scholarly journals Induction of final oocyte maturation in Cyprinidae fish by hypothalamic factors: a review

2009 ◽  
Vol 54 (No. 3) ◽  
pp. 97-110 ◽  
Author(s):  
P. Podhorec ◽  
J. Kouril
Keyword(s):  
Luteinizing Hormone ◽  
Oocyte Maturation ◽  
Hormone Secretion ◽  
Inhibitory Effect ◽  
Gonadotropin Releasing Hormone ◽  
Luteinizing Hormone Secretion ◽  
Releasing Hormone ◽  
Final Oocyte Maturation ◽  
In Captivity ◽  
Lh Secretion

Gonadotropin-releasing hormone in Cyprinidae as in other Vertebrates functions as a brain signal which stimulates the secretion of luteinizing hormone from the pituitary gland. Two forms of gonadotropin-releasing hormone have been identified in cyprinids, chicken gonadotropin-releasing hormone II and salmon gonadotropin-releasing hormone. Hypohysiotropic functions are fulfilled mainly by salmon gonadotropin-releasing hormone. The only known factor having an inhibitory effect on LH secretion in the family Cyprinidae is dopamine. Most cyprinids reared under controlled conditions exhibit signs of reproductive dysfunction, which is manifested in the failure to undergo final oocyte maturation and ovulation. In captivity a disruption of endogenous gonadotropin-releasing hormone stimulation occurs and sequentially that of luteinizing hormone, which is indispensible for the final phases of gametogenesis. In addition to methods based on the application of exogenous gonadotropins, the usage of a method functioning on the basis of hypothalamic control of final oocyte maturation and ovulation has become popular recently. The replacement of natural gonadotropin-releasing hormones with chemically synthesized gonadotropin-releasing hormone analogues characterized by amino acid substitutions at positions sensitive to enzymatic degradation has resulted in a centuple increase in the effectiveness of luteinizing hormone secretion induction. Combining gonadotropin-releasing hormone analogues with Dopamine inhibitory factors have made it possible to develop an extremely effective agent, which is necessary for the successful artificial reproduction of cyprinids.

scholarly journals Neural Determinants of Pulsatile Luteinizing Hormone Secretion in Male Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (2) ◽  
Author(s):  
Su Young Han ◽  
Isaiah Cheong ◽  
Tim McLennan ◽  
Allan E Herbison
Keyword(s):  
Luteinizing Hormone ◽  
High Frequency ◽  
Pulse Generator ◽  
Hormone Secretion ◽  
Pulse Frequency ◽  
Male Mice ◽  
Intact Male ◽  
Luteinizing Hormone Secretion ◽  
Pulse Profile ◽  
Lh Secretion

Abstract The gonadotrophin-releasing hormone (GnRH) pulse generator drives pulsatile luteinizing hormone (LH) secretion essential for fertility. However, the constraints within which the pulse generator operates to drive efficient LH pulsatility remain unclear. We used optogenetic activation of the arcuate nucleus kisspeptin neurons, recently identified as the GnRH pulse generator, to assess the efficiency of different pulse generator frequencies in driving pulsatile LH secretion in intact freely behaving male mice. Activating the pulse generator at 45-minute intervals generated LH pulses similar to those observed in intact male mice while 9-minute interval stimulation generated LH profiles indistinguishable from gonadectomized (GDX) male mice. However, more frequent activation of the pulse generator resulted in disordered LH secretion. Optogenetic experiments directly activating the distal projections of the GnRH neuron gave the exact same results, indicating the pituitary to be the locus of the high frequency decoding. To evaluate the state-dependent behavior of the pulse generator, the effects of high-frequency activation of the arcuate kisspeptin neurons were compared in GDX and intact mice. The same stimulus resulted in an overall inhibition of LH release in GDX mice but stimulation in intact males. These studies demonstrate that the GnRH pulse generator is the primary determinant of LH pulse profile and that a nonlinear relationship exists between pulse generator frequency and LH pulse frequency. This may underlie the ability of stimulatory inputs to the pulse generator to have opposite effects on LH secretion in intact and GDX animals.

scholarly journals Possible Relationship between Long-Term Adverse Health Effects of Gonad-Removing Surgical Sterilization and Luteinizing Hormone in Dogs

Animals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 599
Author(s):  
Michelle A. Kutzler
Keyword(s):  
Luteinizing Hormone ◽  
Cruciate Ligament ◽  
Transitional Cell ◽  
Reproductive Function ◽  
Receptor Activation ◽  
Main Role ◽  
Nitric Oxide Release ◽  
Neoplastic Tissues

Spaying and neutering dogs is commonly used to prevent the birth of unwanted animals and eliminate the risk of reproductive diseases. However, removal of the gonads prevents the feedback of estrogen and testosterone on the pituitary and hypothalamus. As a result, luteinizing hormone (LH) is continuously elevated at supraphysiologic concentrations. Although the main role of LH is for reproductive function (e.g., ovulation), there are LH receptors present in several normal tissues including the thyroid and adrenal glands, gastrointestinal tract, cranial cruciate ligament and round ligament, and lymphocytes. In addition, there are LH receptors present in several neoplastic tissues (e.g., lymphoma, hemangiosarcoma, mastocytoma, transitional cell carcinoma, and osteosarcoma). The role of LH receptors in non-reproductive normal and neoplastic tissues is not known but may stimulate nitric oxide release and induce cell division. The precise etiology of the increased incidence of several non-reproductive long-term health complications following spaying and neutering is not known but may be related to LH receptor activation in these non-reproductive target tissues. How these effects may be mediated is described in this review.

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