Minireview: kisspeptin neurons as central processors in the regulation of gonadotropin-releasing hormone secretion.
ABSTRACT The Kiss1 gene encodes a family of peptides called kisspeptins, which bind to the G protein-coupled receptor GPR54. Kisspeptin(s) and its receptor are expressed in the forebrain, and the discovery that mice and humans lacking a functional GPR54 fail to undergo puberty and exhibit hypogonadotropic hypogonadism implies that kisspeptin signaling plays an essential role in reproduction. Studies in several mammalian species have shown that kisspeptins stimulate the secretion of gonadotropins from the pituitary by stimulating the release of GnRH from the forebrain after the activation of GPR54, which is expressed by GnRH neurons. Kisspeptin is expressed abundantly in the arcuate nucleus (Arc) and the anteroventral periventricular nucleus (AVPV) of the forebrain. Both estradiol and testosterone regulate the expression of the Kiss1 gene in the Arc and AVPV; however, the response of the Kiss1 gene to these steroids is exactly opposite between these two nuclei. Estradiol and testosterone down-regulate Kiss1 mRNA in the Arc and up-regulate its expression in the AVPV. Thus, kisspeptin neurons in the Arc may participate in the negative feedback regulation of gonadotropin secretion, whereas kisspeptin neurons in the AVPV may contribute to generating the preovulatory gonadotropin surge in the female. Hypothalamic levels of Kiss1 and GPR54 mRNA increase dramatically at puberty, suggesting that kisspeptin signaling could mediate the neuroendocrine events that trigger the onset of puberty. Together, these observations demonstrate that kisspeptin-GPR54 signaling in the brain serves as an important conduit for controlling GnRH secretion in the developing and adult animal.
- SourceAvailable from: Alan D Rogol[Show abstract] [Hide abstract]
ABSTRACT: Complex mechanisms exist in the human to defend against adverse effects of negative energy balance. These include alterations of hormone secretion affecting the growth hormone/insulin-like growth factor system, the adrenal axis, and the reproductive system, particularly in females. Energy deficits are least partially offset by neuroendocrine mechanisms regulating appetite and satiety. The complex feedback mechanisms reporting peripheral fat and energy stores to the central nervous system involve secretion of the peptide hormones leptin and ghrelin, which act centrally on neurons in the arcuate nucleus and anteroventral periventricular area. In addition to appetite regulation, these hormones exert influences on spatially and functionally-related mechanisms regulating reproductive function, such as the kisspeptin-gonadotropin releasing hormone system. Negative energy balance often occurs partially as a result of strenuous and repetitive physical exercise. Exercise stress leads to increased cortisol secretion, but this action is mediated through the induced negative energy balance. In healthy adults with energy deficits, this exercise-induced stress appears to be more important than pure psychological stress in impairing reproductive function. Estrogen deficiency resulting from negative energy balance has important adverse effects on bone density as well as bone microarchitecture, and it may also adversely affect markers of cardiovascular disease.Metabolism: clinical and experimental 02/2013; · 3.10 Impact Factor
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ABSTRACT: Objective: Bisphenol A (BPA) is an industrial chemical, particularly used to harden plastics. BPA is thought to have negative health effects on both laboratory animals and humans. Consider ing the decline in age of onset of puberty noted in recent years, particularly among girls, the importance of BPA as an estrogenic endocrine disruptor has increased. In this study, we aimed to determine urinary BPA levels in girls with idiopathic central precocious puberty (ICPP). Methods: Non-obese girls newly diagnosed with ICPP (n=28, age 4-8 years) constituted the study group. The control group consisted of 25 healthy age-matched girls with no history of ICPP or any other endocrine disorder. Urinary BPA levels were measured by using high-performance liquid chromatography.Results: In the ICPP group, urinary BPA levels were significantly higher compared to the control group [median 8.34 (0.84-67.35) μg/g creatinine and 1.62 (0.3-25.79) μg/g creatinine, respectively (OR=8.68, 95% CI:2.03-32.72, p=0.001)]. There was no marked correlation between urinary BPA levels and body mass index in either group. In the ICPP group, no significant correlations were found between urinary BPA levels and serum luteinizing hormone, follicle-stimulating hormone and estradiol levels. Conclusions: To our knowledge, this is the first study evaluating the urinary BPA levels in Turkish girls with ICPP. Our results indicate that the estrogenic effects of BPA may be an etiologic factor in ICPP.Journal of Clinical Research in Pediatric Endocrinology 03/2014; 6(1):16-21.
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ABSTRACT: Stress is known to be an inhibitor of the reproductive hypothalamic-pituitary-gonadal (HPG) axis. However, the neural and molecular connections between stress and reproduction are not yet understood. It is well established that in both humans and rodents, kisspeptin (encoded by the kiss1 gene) is a strong stimulator of the HPG axis. In the present study we hypothesized that endocannabinoids, an important neuromodulatory system in the brain, can act on the HPG axis at the level of kiss1 expression to inhibit reproductive function under stress. Adult male Wistar rats were unilaterally implanted with an intracerebroventricular cannula. Afterwards, the animals were exposed to immobilization stress, with or without the presence of the cannabinoid CB1 receptor antagonist AM251 (1 µg/rat). Blood samples were collected through a retro-orbital plexus puncture before and after stress. Five hours after the stress, brain tissue was collected for reverse transcriptase-quantitative polymerase chain reaction measurements of kiss1 mRNA. Immobilization stress (1 hour) resulted in a decrease in the serum luteinizing hormone concentration. Additionally, kiss1 gene expression was decreased in key hypothalamic nuclei that regulate gonadotrophin secretion, the medial preoptic area (mPOA), and to some extent the arcuate nucleus (ARC). A single central administration of AM251 was effective in blocking these inhibitory responses. These findings suggest that endocannabinoids mediate, at least in part, immobilization stress-induced inhibition of the reproductive system. Our data suggest that the connection between immobilization stress and the HPG axis is kiss1 expression in the mPOA rather than the ARC.Clinical and experimental reproductive medicine. 12/2013; 40(4):155-62.