kiss1-protein--human and Anorexia-Nervosa

The pulsatility of GnRH release is essential for reproductive function. The key events in reproductive function, such as puberty onset and ovulatory cycles, are regulated by the frequency and amplitude modulation of pulsatile GnRH release. Abnormal patterns of GnRH pulsatility are seen in association with disease states, such as polycystic ovarian syndrome and anorexia nervosa. Recent studies with physiological, track-tracing, optogenetic and electrophysiological recording experiments indicate that a group of kisspeptin neurons in the arcuate nucleus (ARC) of the hypothalamus are responsible for pulsatile GnRH release. Thus, the kisspeptin neuron in the ARC has been called the "GnRH pulse-generator." However, a few pieces of evidence do not quite fit into this concept. This article reviews some old works and discusses unresolved issues on the mechanism of GnRH pulse generation.

Topics: Animals; Anorexia Nervosa; Female; Gonadotropin-Releasing Hormone; Kisspeptins; Polycystic Ovary Syndrome; Primates; Reproduction; Sexual Maturation

Due to the dynamic development of molecular neurobiology and bioinformatic methods several novel brain neuropeptides have been identified and characterized in recent years. Contemporary techniques of selective molecular detection e.g. in situ Real-Time PCR, microdiffusion and some bioinformatics strategies that base on searching for single structural features common to diverse neuropeptides such as hidden Markov model (HMM) have been successfully introduced. A convincing majority of neuropeptides have unique properties as well as a broad spectrum of physiological activity in numerous neuronal pathways including the hypothalamus and limbic system. The newly discovered but uncharacterized regulatory factors nesfatin-1, phoenixin, spexin and kisspeptin have the potential to be unique modulators of stress responses and eating behaviour. Accumulating basic studies revelaed an intriguing role of these neuropeptides in the brain pathways involved in the pathogenesis of anxiety behaviour. Nesfatin-1, phoenixin, spexin and kisspeptin may also distinctly affect the energy homeostasis and modulate food intake not only at the level of hypothalamic centres. Moreover, in patients suffered from anxiety and anorexia nervosa a significant, sex-related changes in the plasma neuropeptide levels occurred. It should be therefore taken into account that the targeted pharmacomodulation of central peptidergic signaling may be potentially helpful in the future treatment of certain neuropsychiatric and metabolic disorders. This article reviews recent evidence dealing with the hypothetical role of these new factors in the anxiety-related circuits and pathophysiology of anorexia nervosa.

Topics: Anorexia Nervosa; Anxiety; Biomarkers; Calcium-Binding Proteins; DNA-Binding Proteins; Humans; Hypothalamic Hormones; Hypothalamus; Kisspeptins; Nerve Tissue Proteins; Neuropeptides; Nucleobindins; Peptide Hormones; Signal Transduction

Leptin, a key hormone in energy homeostasis and neuroendocrine function, has a permissive role in initiating puberty and is crucial in the pathogenesis of reproductive dysfunction in several disease states of energy imbalance. KiSS1 neurons have recently been suggested to mediate leptin's effect on the reproductive system. New insights from recent animal studies and clinical trials are discussed.. Alterations in the expression profile of the KiSS1 gene and the kisspeptin receptor have been linked to reproductive dysfunction in leptin-deficient states. Neuroendocrine, including reproductive, dysfunction can be restored in humans and animals by leptin-replacement therapy. These insights have significantly advanced our understanding of hormonal systems needed to maintain normal reproduction. These data, if confirmed, also suggest a role for leptin as a novel therapeutic approach in several disease states.. Recent proof-of-concept studies involving leptin administration to humans underline the critical role of leptin not only in regulating energy homeostasis, but also in maintaining normal reproductive function. Leptin-replacement therapy is currently under intensive investigation as a potential novel therapeutic option for several conditions associated with reproductive dysfunction due to hypoleptinemia.

Topics: Amenorrhea; Animals; Anorexia Nervosa; Energy Metabolism; Female; Gonads; Humans; Hypothalamo-Hypophyseal System; Infertility; Kisspeptins; Leptin; Male; Menarche; Obesity; Polycystic Ovary Syndrome; Puberty; Reproduction; Sex Characteristics; Tumor Suppressor Proteins

It is hypothesized that novel neuropeptides such as phoenixin (PNX), spexin (SPX), and kisspeptin (KISS) are involved in the pathogenesis of eating disorders. The study presented here analyzed neuropeptide concentrations during the course of anorexia nervosa (AN) and aimed to correlate those values with anthropometric and psychometric measurements.. A longitudinal study was carried outin 30 AN adolescent patients and 15 age-matched healthy female controls. Selected neuroprotein serum levels were analyzed in malnourished patients (accAN) and following partial weight recovery (norAN), and these values were compared with the control group.. In accAN patients, decreased serum PNX levels were detected while SPX serum concentrations were lower in the accAN and norAN patients. No differences were observed in KISS concentrations in all studied groups.. In malnourished adolescent inpatients with AN, serum PNX and SPX level were decreased. The partial weight recovery normalized PNX concentrations but failed to normalize SPX levels. Therefore these two neuropeptides might be crucial for the etiology and course of the AN. The KISS levels did not change in the course of AN. The PNX levels were associated with some symptoms of eating disorders which may indicate its potential contribution in the regulation of emotions and behaviors in AN.

Topics: Adolescent; Anorexia Nervosa; Female; Humans; Inpatients; Kisspeptins; Longitudinal Studies; Neuropeptides; Peptide Hormones

Kisspeptin is one of the most potent stimulators of GnRH secretion and consequent gonadotropin release from the anterior pituitary. Kisspeptin is considered critical in regulating reproductive function in relation to metabolic cues. Reproductive function is gated by the energy reserves of the individual. Conditions of energy insufficiency, such as Anorexia Nervosa, often disturb reproductive function and fertility.. The aim of this research was to investigate similar or comparable hormonal patterns in kisspeptin mechanics using computational methodology tools.. Twenty-two females with typical or atypical anorexia nervosa and fifteen control females, were recruited from the Center for Adolescent Medicine of the University of Athens. Serum levels of Prolactin (PRL), 17-Hydroxy-Progesterone (17OHPR), Free Triiodothyronine (FT3), Triiodothyronine (T3), Free Thyroxine (FT4), Thyroid Stimulating Hormone (TSH), Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH) and Estradiol (E2) were measured in patients and controls. Data were modelled computationally in order to find similar or comparable patterns between control and anorexic participants, with respect to kisspeptin.. Kisspeptin manifested symmetrical regression plots between controls and anorexics with respect to 17OHPR, LH and FSH, as well as a threshold pattern among controls, typical and atypical anorexics.. Kisspeptin seems to participate in the anorexic hormonal milieu through threshold or symmetrical mechanisms.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Anorexia Nervosa; Case-Control Studies; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Kisspeptins; Luteinizing Hormone; Pituitary Gland, Anterior; Prolactin; Regression Analysis; Thyroxine; Triiodothyronine; Young Adult

Anorexia nervosa (AN) is a disorder characterized by extreme restriction of food intake and incorrect perception of patients' body, its weight and shape. Patients diagnosed with anorexia nervosa apart from an eating disorder are characterized also by hypothalamic amenorrhea. Many neuropeptides and neurotransmitters play an important role in physiological regulation of gonadoliberin (GnRH) secretion.. The aim of the study is to assess the role of kisspeptin in the etiology of anorexia nervosa.. The study was classified as 55 women aged from 17 to 28 years old. Patients were classified into two groups: study group consisted of 15 patients diagnosed with AN and control group consisted of 40 healthy women. Examination of serum blood from patients was performed by ELISA-enzyme-linked immunosorbent assay. Concentrations of serum kisspeptin, FSH, LH, estradiol, prolactin, testosterone were analyzed in patients from study and control group.. The average body weight of patients with AN was 45.0±7.56 kg and was statistically significantly lower compared to women in the control group (61.1±7.20 kg) (p=0.0001). The average serum concentration of kisspeptin in patients with AN was 0.20±0.07 ng/ml, in women in the control group was 0.3±0.36 ng/ml (p=0.712). Serum LH concentrations in patients with AN was 2.5±1.71 mIU/ml and was statistically significantly lower compared to women in the control group (13.5±9.73 mIU/ml) (p=0.0001). The mean serum estradiol concentrations in patients with AN were 31.0±15.3 pg/ml and were statistically significantly lower compared to the control group (129.0±107.7 pg/ml) (p=0.0001).. There was not significant difference between serum kisspeptin levels in patients with AN and healthy women. Further research is needed on the role of kisspeptin in AN.

Topics: Adolescent; Adult; Anorexia Nervosa; Estradiol; Female; Follicle Stimulating Hormone; Humans; Kisspeptins; Prolactin; Testosterone; Young Adult

To measure, for the first time, serum kisspeptin concentrations in adolescent females with anorexia nervosa (AN) and associated amenorrhea, and investigate potential correlations of kisspeptin with anthropometric, bone and hormonal data.. Setting: University Adolescent Medicine Center.. Females aged 12-20 years with typical or atypical AN (based on DSM-5 diagnostic criteria) and controls.. Measurement of body mass index (BMI), whole body/lumbar spine bone mineral density and serum concentrations of kisspeptin, follicle stimulating hormone, luteinizing hormone (LH), prolactin (PRL), thyroid stimulating hormone (TSH), free thyroxine, triiodothyronine, estradiol (E2), 17-hydroxyprogesterone.. Kisspeptin serum concentrations and correlations between kisspeptin and AN-related anthropometric, bone and hormonal changes.. Participants included 37 females, 22 with AN (typical AN group=17, atypical AN group=5) and 15 in the control group. All typical AN patients had secondary amenorrhea. Wide inter-subject variation (101.9-709.1 ng/L) in kisspeptin levels was observed with no significant differences among study groups; there was a trend toward higher concentrations in the atypical AN group. Adolescents with typical AN had significantly lower BMI (P<0.001), lumbar spine z-score (P=0.016), serum E2 (P<0.001), LH (P=0.016), PRL (P=0.034) and TSH (P=0.045) than controls. They also had lower BMI (P=0.009) and TSH (P=0.027) than girls with atypical AN. An inverse correlation between BMI and serum kisspeptin was noted in the typical AN group (r=-0.60, P=0.012).. Serum kisspeptin concentrations overlapped between patients and controls; in typical anorexic adolescents kisspeptin concentrations were negatively correlated with BMI. Future studies are needed to explore kisspeptin physiology in AN.

Topics: Adolescent; Amenorrhea; Anorexia Nervosa; Body Mass Index; Case-Control Studies; Child; Female; Humans; Kisspeptins; Young Adult

Topics: Actigraphy; Adiposity; Adolescent; Adult; Amenorrhea; Anorexia Nervosa; Anxiety; Body Mass Index; Female; Germany; Ghrelin; Humans; Hyperkinesis; Kisspeptins; Middle Aged; Motor Activity; Psychomotor Agitation; Severity of Illness Index; Thinness; Young Adult