Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes

Rance, Naomi E.; Dacks, Penny A.; Mittelman-Smith, Melinda A.; Romanovsky, Andrej A.; Krajewski-Hall, Sally J.

doi:10.1016/j.yfrne.2013.07.003

Cited by 266 publications

(216 citation statements)

References 193 publications

Supporting

Mentioning

191

Contrasting

Unclassified

Order By: Relevance

“…Rapid estrogen withdrawal appears to mediate flushes in women via an increase in release of neurokinin B, and possibly other mediators, from the hypothalamus (Jayasena et al 2015). Neurokinin B acts on neurokinin 3 receptors in the hypothalamic median preoptic nucleus, to stimulate heat dissipation effectors such as cutaneous vasodilatation, diaphoresis and coldseeking behaviour (Rance et al 2013, Jayasena et al 2015. In perimenopausal and postmenopausal women, estrogen replacement is the most effective pharmaceutical strategy for mitigating hot flushes (Nelson 2004), although an oral neurokinin 3 receptor antagonist recently appears promising (Prague et al 2017).…”

Section: Effect Of Estradiol On Vasomotor Symptomsmentioning

confidence: 99%

Estradiol for the mitigation of adverse effects of androgen deprivation therapy

Russell

Cheung

Grossmann

2017

Endocrine-Related Cancer

View full text Add to dashboard Cite

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men. Conventional endocrine treatment for PCa leads to global sex steroid deprivation. The ensuing severe hypogonadism is associated with well-documented adverse effects. Recently, it has become apparent that many of the biological actions attributed to androgens in men are in fact not direct, but mediated by estradiol. Available evidence supports a primary role for estradiol in vasomotor stability, skeletal maturation and maintenance, and prevention of fat accumulation. Hence there has been interest in revisiting estradiol as a treatment for PCa. Potential roles for estradiol could be in lieu of conventional androgen deprivation therapy or as low-dose add-back treatment while continuing androgen deprivation therapy. These strategies may limit some of the side effects associated with conventional androgen deprivation therapy. However, although available data are reassuring, the potential for cardiovascular risk and pro-carcinogenic effects on PCa via estrogen receptor signalling must be considered.

show abstract

Section: Effect Of Estradiol On Vasomotor Symptomsmentioning

confidence: 99%

Estradiol for the mitigation of adverse effects of androgen deprivation therapy

Russell

Cheung

Grossmann

2017

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…Post-menopausal women have been shown to demonstrate hypertrophy of these neurons in the hypothalamic arcuate nucleus, changes that have also been demonstrated in young monkeys after ovariectomy and reversed by oestrogen replacement (15). Animal models have studied the connections between KNDy neurons and the pathways that control heat-defence effectors involving the preoptic structures (16) and have also evaluated the thermoregulatory effects of ablating KNDy neurons, indicating that KNDy neurons facilitate cutaneous vasodilatation, an important heat dissipation effector (17). Based on these previous investigations, Prage et al very recently reported a randomised doubleblind placebo-controlled trial, using an oral neurokinin 3 receptor antagonist (MLE4901).…”

Section: Neural Mechanism: Wet Flushingmentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Flushing: current concepts

Huguet

Grossman

2017

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: Flushing can be defined as a sensation of warmth accompanied by erythema that most commonly is seen on the face and which occurs in episodic attacks. Such a problem can be clinically problematic, since many conditions and drugs can be related to flushing, and while often there appears to be no underlying organic disease, it is important to exclude disorders since they may be life-threatening conditions. Design and methods: We performed a search in MEDLINE using the terms 'flushing' in combination with 'carcinoid syndrome', 'pheochromocytoma', 'mastocytosis', 'menopausal hot flush' and 'treatment'. European and American guidelines relating to neuroendocrine tumours, mastocytosis and menopause were reviewed. Results: In this review, we discuss the main causes of flushing and propose an algorithm based on pathogenesis, which can be used to guide the clinical evaluation process. We also review recent significant developments in the assessment and treatment of the carcinoid syndrome and menopausal hot flushes, which should guide the clinical practice regarding this common but sometimes confusing condition. Conclusions: When evaluating flushing, a precise systematic approach is needed to exclude potentially serious underlying causes, although despite this, the cause of the disorder is not always found. If symptoms are not progressive, the patient should be advised about its apparently benign nature in order to avoid unnecessary studies or initiating treatments of minimal benefit.

show abstract

“…In a recent randomised trial researchers found that NKB antagonist (AZD4901) administration in patients having PCOS resulted in reduced LH pulse frequency and secretion with subsequent remarkable and sustained reduction in testosterone levels [183]. Likewise, kisspeptin and NKB antagonists might be helpful in treating patients having precocious puberty [1] with the additional benefit of reduced menopausal side effects [184][185][186].…”

Section: Clinical Utility Of Kisspeptins In Reproductionmentioning

confidence: 99%

Rola sygnalizacji kisspeptyny w osi podwzgórze–przysadka–nadnercza — aktualna perspektywa

Javed

Qamar

Sathyapalan

2015

Endokrynologia Polska

View full text Add to dashboard Cite

The discovery of kisspeptins in the recent past remoulded current understanding of the neuroendocrine axis relating to the regulation of human puberty and reproduction. Kisspeptins have been recognised to act upstream of GnRH and have been shown to play a vital role in the control of the hypothalamic-pituitary-gonadal axis via regulation of gonadotrophin secretion, onset of puberty, and control of fertility. KNDy (kisspeptin/neurokinin-B/dynorphin) neurons have been suggested to modulate GnRH pulsatile secretion, which is required to support reproductive function in both sexes. They have also been involved in mediating both positive and negative sex steroid feedback signals to GnRH neurons and serve as a vital connection between reproduction and metabolic status of the body. When kisspeptin is administered to healthy humans, and in patients with reproductive disorders, it strongly and directly stimulates GnRH and subsequent LH secretion and enhances LH pulse frequency. These observations suggest that kisspeptins are a potential novel therapeutic approach for treating disorders with either pathologically reduced or augmented gonadotrophins pulsatile secretion and is currently a focus of translational research. Kisspeptins have also been identified in several peripheral reproductive organs, indicating their role in modulation of ovarian function, embryo implantation, and placentation, but a great deal of work remains to be done to explore further in this regard, and the evidence is only available from studies done on animal models. In this review we will mainly focus on current available evidence related to the role of kisspeptins in controlling GnRH pulse frequency, specifically their role in puberty, fertility, and reproduction. We will also be appraising other factors that regulate the kiSS1/Kisspeptin/GPR-54 system. StreszczenieOdkrycie kisspeptyn, które miało miejsce całkiem niedawno, odmieniło obecne rozumienie osi neuroendokrynnej, związanej z regulacją okresu dojrzewania i rozrodu. Odkryto, że kisspeptyny działają przed GnRH i odgrywają istotną rolę w kontroli osi podwzgórze-przysadka-nadnercza poprzez regulację wydzielania gonadotropiny, rozpoczęcia okresu dojrzewania oraz kontroli płodności. Zasugerowano, że komórki KNDy (kisspeptyna/neurokinina-B/dynorfina) modulują pulsacyjne uwalnianie GnRH, wymagane, aby wspomagać funkcję rozrodczą u obu płci. Komórki te są również zaangażowane w przekazywanie zarówno pozytywnych, jak i negatywnych sygnałów hormonów płciowych do neuronów GnRH, a także stanowią kluczowe połączenie między reprodukcją i stanem metabolicznym ciała. Kiedy kisspeptyna jest podawana jednostkom zdrowym i pacjentom z zaburzeniami płodności, silnie i bezpośrednio stymuluje GnPH i dalsze uwalnianie LH oraz poprawia częstotliwość impulsów LH. Obserwacje te przedstawiają kisspeptyny jako nowe potencjalne terapeutyczne podejście w leczeniu zaburzeń patologicznie obniżonego lub zwiększonego pulsacyjnego uwalniania gonadotropin i obecnie stanowi główny punkt zainteresowania badań przekładaj...

show abstract

Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes

Cited by 266 publications

References 193 publications

Estradiol for the mitigation of adverse effects of androgen deprivation therapy

Estradiol for the mitigation of adverse effects of androgen deprivation therapy

MANAGEMENT OF ENDOCRINE DISEASE: Flushing: current concepts

Rola sygnalizacji kisspeptyny w osi podwzgórze–przysadka–nadnercza — aktualna perspektywa

Contact Info

Product

Resources

About