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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fertility is gated by nutrition and the availability of stored energy reserves, but the cellular and molecular mechanisms that link energy stores and reproduction are not well understood. Neuropeptides including galanin-like peptide (GALP), neuropeptide Y (NPY), products of the proopiomelanocortin (POMC; e.g., alpha-MSH and beta-endorphin), and kisspeptin are thought to be involved in this process for several reasons. First, the neurons that express these neuropeptides all reside in the hypothalamic arcuate nucleus, a critical site for the regulation of both metabolism and reproduction. Second, these neuropeptides are all targets for regulation by metabolic hormones, such as leptin and insulin. And third, these neuropeptides have either direct or indirect effects on feeding and metabolism, as well as on the secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH). As the target for the action of metabolic hormones and sex steroids, these neuropeptides serve as molecular motifs integrating the control of metabolism and reproduction.
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PMID:Neuropeptide signaling in the integration of metabolism and reproduction. 1789 35

Kisspeptin neurones in the arcuate nucleus play a pivotal role in the regulation of hypothalamic gonadotrophin-releasing hormone (GnRH) secretion in higher primates. To examine whether kisspeptin also influences the function of the primate pituitary directly, two experiments were performed in adult male rhesus monkeys. First, the distribution of kisspeptin-containing cells in the pituitary was described using fluorescence immunohistochemistry. Second, the secretion of non-gonadotrophin adenohypophysial hormones [growth hormone (GH), prolactin and thyroid-stimulating hormone (TSH)] and cortisol in response to i.v. kisspeptin administration was examined. Eight animals were deeply anaesthetised and transcardially perfused with 4% paraformaldehyde. Fluorescence immunohistochemistry was performed on 25-microm thick free-floating pituitary sections to localise immunopositive kisspeptin cells and to examine their relationship with immunostaining for luteinising hormone (LH), follicle-stimulating hormone, GH, prolactin, alpha-melanocyte-stimulating hormone (MSH), adrenocorticotrophic hormone (ACTH) and GnRH. Kisspeptin cells were found in the intermediate lobe of all animals and, in four monkeys, this neuropeptide was also observed in cells scattered in the periphery of the anterior lobe. Kisspeptin colocalised with alpha-MSH-immunopositive cells in the intermediate lobe and, in 50% of the monkeys, with ACTH-immuunopositive cells in the periphery of the adenohypophysis. There was no evidence for colocalisation of kisspeptin with gonadotrophs, somatotrophs or lactotrophs. Beaded kisspeptin axons were observed in the neural lobe. In addition, assay of plasma samples that had been collected for a previous study documenting kisspeptin-10-induced LH release in male monkeys revealed that kisspeptin administration failed to influence circulating concentrations of GH, prolactin, TSH and cortisol. Release of all four of these non-gonadotrophic hormones, however, was stimulated markedly by NMDA, which is considered to act centrally. Although the morphological findings obtained in the present study are consistent with the notion that kisspeptin may act directly at the level of the pituitary, the nature of such an action remains to be defined.
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PMID:Studies of the localisation of kisspeptin within the pituitary of the rhesus monkey (Macaca mulatta) and the effect of kisspeptin on the release of non-gonadotropic pituitary hormones. 1968 51

The hypothalamo-pituitary-adrenal (HPA) and hypothalamo-pituitary-gonadal (HPG) axes have an intricate cross talk that results in the inhibition of reproductive functions during periods of chronic physiological or psychological stress. Recent studies have shown that kisspeptin neurons have projections to many non-reproductive areas of the brain including the paraventricular nucleus (PVN) of the hypothalamus, thereby providing evidence of an anatomical framework for kisspeptin to regulate the HPA axis. In this study, we tested as to whether kisspeptin modulates the HPA axis at three potential levels of regulation: (1) transcription of stress-related genes CRH, AVP, and oxytocin (OXY); (2) release of neuropeptides from PVN-derived neuronal cells via mobilization of intracellular calcium stores; and (3) in vivo regulation of the HPA axis under basal and stress-induced conditions in adult male rats. Overall, our data showed that kisspeptin did not alter basal, or stress-induced HPA axis activity (plasma corticosterone (CORT) and adrenocorticotropin hormone (ACTH)) in adult male rats and had modest, yet significant effects on CRH, AVP, and OXY gene expressions.
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PMID:Effects of kisspeptin on parameters of the HPA axis. 2138 28

It is now well established that the kisspeptin neurons of the hypothalamus play a key role in regulating the activity of gonadotropin-releasing hormone (GnRH) neurons. The population of kisspeptin neurons residing in the rostral periventricular region of the third ventricle (RP3V), encompassing the anteroventral periventricular (AVPV) and periventricular preoptic nuclei (PVpo), are implicated in the generation of the preovulatory GnRH surge mechanism and puberty onset in female rodents. The present study examined whether these kisspeptin neurons may express other neuropeptides in the adult female mouse. Initially, the distribution of galanin, neurotensin, met-enkephalin (mENK), and cholecystokinin (CCK)-immunoreactive cells was determined within the RP3V of colchicine-treated mice. Subsequent experiments, using a new kisspeptin-10 antibody raised in sheep, examined the relationship of these neuropeptides to kisspeptin neurons. No evidence was found for expression of neurotensin or CCK by RP3V kisspeptin neurons, but subpopulations of kisspeptin neurons were observed to express galanin and mENK. Dual-labeled RP3V kisspeptin/galanin cells represented 7% of all kisspeptin and 21% of all galanin neurons whereas dual-labeled kisspeptin/mENK cells represented 28-38% of kisspeptin neurons and 58-68% of the mENK population, depending on location within the AVPV or PVpo. Kisspeptin neurons in the arcuate nucleus were also found to express galanin but not mENK. These observations indicate that, like the kisspeptin population of the arcuate nucleus, kisspeptin neurons in the RP3V also co-express a range of neuropeptides. This pattern of co-expression should greatly increase the dynamic range with which kisspeptin neurons can modulate the activity of their afferent neurons.
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PMID:Kisspeptin neurons co-express met-enkephalin and galanin in the rostral periventricular region of the female mouse hypothalamus. 2180 Feb 99

The Damaraland mole-rat is a subterranean mammal exhibiting extreme reproductive skew with a single reproductive female in each colony responsible for procreation. Non-reproductive female colony members are physiologically suppressed while in the colony, exhibiting reduced concentrations of plasma luteinizing hormone (LH) and a decreased response of the pituitary, as measured by the release of bioactive LH, to an exogenous dose of gonadotrophin releasing hormone (GnRH). Removal of the reproductive female from the colony results in an elevation of LH and an enhanced response of the pituitary to a GnRH challenge in non-reproductive females comparable to reproductive females, implying control of reproduction in these individuals by the reproductive female. The Damaraland mole-rat is an ideal model for investigating the physiological and behavioral mechanisms that regulate the hypothalamo-pituitary-gonadal axis. In contrast, we know less about the control of reproduction at the level of the hypothalamus. The immunohistochemistry of the GnRH system of both reproductive and non-reproductive female Damaraland mole-rats has revealed no significant differences with respect to morphology, distribution or numbers of immunoreactive GnRH perikarya. We examined whether the endogenous opioid peptide beta-endorphin was responsible for the inhibition of the release of the GnRH from the neurons indirectly by measuring LH concentrations in these non-reproductive females following single, hourly and 8 hourly injections of the opioid antagonist naloxone. The results imply that the endogenous opioid peptide, beta-endorphin, is not responsible for the inhibition of GnRH release from the perikarya in non-reproductive females. Preliminary data examining the circulating levels of cortisol also do not support a role for circulating glucocorticoids. The possible role of kisspeptin is discussed.
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PMID:Teasing apart socially-induced infertility in non-reproductive female Damaraland mole-rats, Fukomys damarensis (Rodentia: Bathyergidae). 2218 23

Kisspeptin, a neuropeptide encoded by Kiss1 gene, plays pivotal roles in the regulation of reproductive function. Recently various stressors and stress-induced molecules such as corticotropin-releasing hormone (CRH) and corticosterone have been shown to inhibit Kiss1 expression in rat hypothalamus. To determine whether CRH and glucocorticoids directly act on kisspeptin neurons, we examined the colocalization of CRH receptor (CRH-R) and glucocorticoid receptor (GR) in kisspeptin neurons in the female rat hypothalamus. Double-labeling immunohistochemistry revealed that most kisspeptin neurons in the anteroventral periventricular nucleus and periventricular nucleus continuum (AVPV/PeN), and arcuate nucleus (ARC) expressed CRH-R. We also observed a few close appositions of CRH immunoreactive fibers on some of kisspeptin neurons in AVPV/PeN and ARC. On the other hand, most kisspeptin neurons in AVPV/PeN expressed GR, whereas only a few of kisspeptin neurons in ARC expressed GR. Altogether, our study provides neuroanatomical evidence of the direct modulation of kisspeptin neurons by CRH and glucocorticoids and suggests that stress-induced CRH and glucocorticoids inhibit gonadotropin secretion via the kisspeptin system.
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PMID:Immunohistochemical analysis of the colocalization of corticotropin-releasing hormone receptor and glucocorticoid receptor in kisspeptin neurons in the hypothalamus of female rats. 2306 71

Cocaine- and amphetamine-regulated transcript (CART) is a hypothalamic neuropeptide implicated in both metabolic and reproductive regulation, raising the possibility that CART plays a role in reproductive inhibition during negative metabolic conditions. The current study characterized CART's regulatory influence on GnRH and kisspeptin (Kiss1) cells and determined the sensitivity of different CART populations to negative energy balance. CART fibers made close appositions to 60% of GnRH cells, with the majority of the fibers (>80%) originating from the arcuate nucleus (ARH) CART/pro-opiomelanocortin population. Electrophysiological recordings in GnRH-green fluorescent protein rats demonstrated that CART postsynaptically depolarizes GnRH cells. CART fibers from the ARH were also observed in close contact with Kiss1 cells in the ARH and anteroventral periventricular nucleus (AVPV). Recordings in Kiss1-GFP mice demonstrated CART also postsynaptically depolarizes ARH Kiss1 cells, suggesting CART may act directly and indirectly, via Kiss1 populations, to stimulate GnRH neurons. CART protein and mRNA levels were analyzed in 2 models of negative energy balance: caloric restriction (CR) and lactation. Both CART mRNA levels and the number of CART-immunoreactive cells were suppressed in the ARH during CR but not during lactation. AVPV CART mRNA was suppressed during CR, but not during lactation when there was a dramatic increase in CART-immunoreactive cells. These data suggest differing regulatory signals of CART between the models. In conclusion, both morphological and electrophysiological methods identify CART as a novel and potent stimulator of Kiss1 and GnRH neurons and suppression of CART expression during negative metabolic conditions could contribute to inhibition of the reproductive axis.
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PMID:Cocaine- and amphetamine-regulated transcript is a potent stimulator of GnRH and kisspeptin cells and may contribute to negative energy balance-induced reproductive inhibition in females. 2373 94

Nutrient availability is a determinant of reproductive success. It is well known that inadequate nutrition results in reproductive failure due to a number of factors including delay of puberty or anoestrous in post-pubertal animals. The lack of nutrients is detected primarily by changes in circulating nutrient molecules and hormones and communicated directly or indirectly to the hypothalamus and brain stem for integration. The general effect is that low nutrition leads to increased appetite stimulation and reduced reproductive performance. When nutrition is adequate, the reverse is true. Both aspects will be the focus of this review. One result of the lack of nutrients is a reduction in luteinizing hormone (LH) concentrations and pulse frequency. Nutrient signals, such as glucose availability, hormonal signals, such as insulin and leptin, and neuroendocrine signals, such as neuropeptide Y and corticotropin-releasing hormone, have been clearly demonstrated to interact to produce changes in LH and reproductive success. Other signals, such as fatty acids, ghrelin, agouti-related peptide, melanin-concentrating hormone, orexin, melanocyte-stimulating hormone, kisspeptin, neurokinin, dynorphin and gonadotropin inhibitory hormone may also play a role in integrating nutrition and reproduction. This review will focus on the major features of the reciprocal control of appetite and reproduction in sheep.
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PMID:Hypothalamic integration of nutrient status and reproduction in the sheep. 2396 14

Kisspeptin is vital for the neuroendocrine regulation of GNRH secretion. Kisspeptin neurons are now recognized as a central pathway responsible for conveying key homeostatic information to GNRH neurons. This pathway is likely to mediate the well-established link between energy balance and reproductive function. Thus, in states of severely altered energy balance (either negative or positive), fertility is compromised, as is Kiss1 expression in the arcuate nucleus. A number of metabolic modulators have been proposed as regulators of kisspeptin neurons including leptin, ghrelin, pro-opiomelanocortin (POMC), and neuropeptide Y (NPY). Whether these regulate kisspeptin neurons directly or indirectly will be discussed. Moreover, whether the stimulatory role of leptin on reproduction is mediated by kisspeptin directly will be questioned. Furthermore, in addition to being expressed in GNRH neurons, the kisspeptin receptor (Kiss1r) is also expressed in other areas of the brain, as well as in the periphery, suggesting alternative roles for kisspeptin signaling outside of reproduction. Interestingly, kisspeptin neurons are anatomically linked to, and can directly excite, anorexigenic POMC neurons and indirectly inhibit orexigenic NPY neurons. Thus, kisspeptin may have a direct role in regulating energy balance. Although data from Kiss1r knockout and WT mice found no differences in body weight, recent data indicate that kisspeptin may still play a role in food intake and glucose homeostasis. Thus, in addition to regulating reproduction, and mediating the effect of energy balance on reproductive function, kisspeptin signaling may also be a direct regulator of metabolism.
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PMID:Kisspeptin and energy balance in reproduction. 2432 38

Environmental stress affects various parts of mammals typically through the circulation of stress hormones. It has been identified as one of the possible reasons for male reproductive difficulties, but the complex mechanisms responsible for stress-induced reproductive suppression are poorly understood. Here, we examined the relationship between chronic environmental stress and hypothalamic kisspeptin, a recently discovered upstream regulator of the reproductive endocrine feedback system. We studied male mice under an unpredictable chronic stress procedure to replicate the situation of animals under chronic stress. Histological and immunohistochemical analyses were performed focusing on kisspeptin neurons in the arcuate hypothalamic nucleus (ARC) and DNA fragmented cells in seminiferous tubules. Although the ARC was not morphologically altered in either the stressed or non-stressed group, granular kisspeptin immunoreactivities decreased slightly in the stress group. In the testes of the stress group, several signs of testicular degeneration were observed, including increased numbers of ssDNA-positive cells per seminiferous tubule, thinning, vacuoled seminiferous epithelia and multinucleated giant cells. The decreases in kisspeptin in the stress group might be due to other hypothalamic peptides, such as corticotropin-releasing hormone and leptin, whose receptors are known to coexpress in the ARC. In addition, environmental stress directly and indirectly affects testicular function through stress hormones and gonadotropins. In summary, our findings enhance the understanding of stress-induced reproductive suppression possibly mediated by kisspeptin in the ARC.
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PMID:Unpredictable chronic stress-induced reproductive suppression associated with the decrease of kisspeptin immunoreactivity in male mice. 2487 49


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