Kisspeptin-54 Stimulates Gonadotropin Release Most Potently during the Preovulatory Phase of the Menstrual Cycle in Women

Dhillo, Waljit S.; Chaudhri, Owais B.; Thompson, Emily L.; Murphy, Kevin G.; Patterson, Michael; Ramachandran, Radha; Nijher, Gurjinder; Amber, Vian; Kokkinos, Alexander; Donaldson, Mandy; Ghatei, Mohammad A.; Bloom, Stephen R.

doi:10.1210/jc.2007-1116

Cited by 254 publications

(240 citation statements)

References 51 publications

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“…Because kisspeptins are known as the most important activators of GnRH neurons (55) and they are able to cause a powerful stimulation in LH and FSH secretion in both humans and animal models (48,(56)(57)(58), kisspeptin administration may have potential therapeutic effects to treat infertility. The first evidence of this effect was provided by a clinical trial in which women with functional hypothalamic amenorrhea were subjected to a protocol of twice-daily sc kisspeptin-54 administration for 2 weeks.…”

Section: May Kisspeptin Be Used As a Novel Therapeutic Approach To Trmentioning

confidence: 99%

Interactions between prolactin and kisspeptin to control reproduction

Donato

Frazão²

2016

Arch. Endocrinol. Metab.

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Prolactin is best known for its effects of stimulating mammary gland development and lactogenesis. However, prolactin is a pleiotropic hormone that is able to affect several physiological functions, including fertility. Prolactin receptors (PRLRs) are widely expressed in several tissues, including several brain regions and reproductive tract organs. Upon activation, PRLRs may exert prolactin's functions through several signaling pathways, although the recruitment of the signal transducer and activator of transcription 5 causes most of the known effects of prolactin. Pathological hyperprolactinemia is mainly due to the presence of a prolactinoma or pharmacological effects induced by drugs that interact with the dopamine system. Notably, hyperprolactinemia is a frequent cause of reproductive dysfunction and may lead to infertility in males and females. Recently, several studies have indicated that prolactin may modulate the reproductive axis by acting on specific populations of hypothalamic neurons that express the Kiss1 gene. The Kiss1 gene encodes neuropeptides known as kisspeptins, which are powerful activators of gonadotropin-releasing hormone neurons. In the present review, we will summarize the current knowledge about prolactin's actions on reproduction. Among other aspects, we will discuss whether the interaction between prolactin and the Kiss1-expressing neurons can affect reproduction and how kisspeptins may become a novel therapeutic approach to treat prolactin-induced infertility. Arch Endocrinol Metab. 2016;60(6):587-95

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Section: May Kisspeptin Be Used As a Novel Therapeutic Approach To Trmentioning

confidence: 99%

Interactions between prolactin and kisspeptin to control reproduction

Donato

Frazão²

2016

Arch. Endocrinol. Metab.

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“…KP-54 stimulated gonadotropins in healthy women and women with hypothalamic amenorrhea but long term treatment induced tachyphylaxis 122 and administration to cycling women showed a greater gonadotropin response during the pre-ovulatory phase of the menstrual cycle 90 . Post-menopausal women had a greater response to KP-10 than women in the follicular phase and women with progestogen implants while women on the combined contraceptive pill did not have a significant response 123 .…”

Section: Potential Therapeutic Applications Of Kp Analoguesmentioning

confidence: 96%

“…administration of KP-10 has similar stimulatory effects on gonadotropin secretion in men over a dose range of 0.01 to 1 μg/kg 88,89 . The stimulatory effect of KP administration to normal women is greatest during the pre-ovulatory phase of the menstrual cycle 90 .…”

Section: Introductionmentioning

confidence: 97%

Current and future applications of GnRH, kisspeptin and neurokinin B analogues

Millar

Newton

2013

Nat Rev Endocrinol

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Reproductive hormones impact on all stages of life from gamete production, fertilisation, fetal development and parturition, neonatal development and puberty through to adulthood and senescence.The reproductive hormone cascade has therefore been the target for the development of numerous drugs which modulate its activity at many levels. As the central regulator of the cascade, gonadotropinreleasing hormone (GnRH) agonists and antagonists have found extensive applications in treating a wide range of hormone-dependent deseases such as precocious puberty, prostate cancer, benign prostatic hyperplasia, endometriosis and uterine fibroids, as well as being an essential component of in vitro fertilisation (IVF) protocols. Recently-discovered neuroendocrine peptides, kisspeptin (KP) and neurokinin B (NKB), have also been identified as therapeutic targets and novel agonists and antagonists are being developed as modulators of the cascade upstream of GnRH. Here we review the development and applications of analogues of the major neuroendocrine peptide regulators of the reproductive hormone cascade, GnRH, KP and NKB.

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“…The possible explanation for in vivo differences between the two isoforms is probably due to dissimilarities in their pharmacokinetic properties. While many studies have been done to explore the kisspeptin pharmacokinetics [99][100][101], the evidence is still not enough to understand the differences completely, although the available data is helpful to interpret the clinical studies being formed using different kisspeptin isoforms.…”

Section: Kisspeptin Pharmacokinetics In Humansmentioning

confidence: 99%

“…Inversely, markedly reduced responses were seen after Kp-10 injection or infusion in the early to mid-follicular phase, the phase in the menstrual cycle having lowest circulating oestrogen levels [100,103], although some studies also found robust LH secretion during mid-luteal phase, which was not as significant as in the preovulatory phase [63]. Similarly, potent LH and FSH responses were observed mainly during the preovulatory period in women after sustained exposure to SC Kp-54 [99]. Intriguingly, a biphasic response was observed during the mid-luteal phase after SC Kp-54, which had been observed previously after long-acting GnRH analogues [104].…”

Section: Effects Of Acute Kisspeptin Administration In Healthy Subjectsmentioning

confidence: 99%

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

Javed

Qamar

Sathyapalan

2015

Endokrynologia Polska

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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...

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Kisspeptin-54 Stimulates Gonadotropin Release Most Potently during the Preovulatory Phase of the Menstrual Cycle in Women

Abstract: Elevation of plasma kisspeptin in human females potently stimulates LH release in the preovulatory phase and provides a novel mechanism for manipulation of the HPG axis in women.

Cited by 254 publications

References 51 publications

Interactions between prolactin and kisspeptin to control reproduction

Interactions between prolactin and kisspeptin to control reproduction

Current and future applications of GnRH, kisspeptin and neurokinin B analogues

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

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