Ultrastructural Evidence of Kisspeptin-Gonadotrophin-Releasing Hormone (GnRH) Interaction in the Median Eminence of Female Rats: Implication of Axo-Axonal Regulation of GnRH Release

Uenoyama, Yoshihisa; Inoue, N.; Pheng, Vutha; Homma, Tetsuya; Takagi, Kenji; Yamada, Shigehiro; Ajiki, Kyoko; Ichikawa, Masumi; Okamura, Hiroaki; Maeda, Kei‐ichiro; Tsukamura, Hiroko

doi:10.1111/j.1365-2826.2011.02199.x

Cited by 97 publications

(89 citation statements)

References 47 publications

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“…It has been demonstrated that the intracerebroventricular administration of KP induces luteinizing hormone (LH) secretion (Thompson et al 2004, Castellano et al 2005. Additionally, mRNA and immunohistochemistry analyses have demonstrated the presence of Kiss1R and KP in the stroma of GnRH neurons in the preoptic area and in axon terminals at the median eminence (Yamada et al 2007, Uenoyama et al 2011. Furthermore, the presence of KP and its actions have been demonstrated in many peripheral organs (Vikman & Ahren 2009, Pinilla et al 2012 such as the ovary.…”

Section: Introductionmentioning

confidence: 99%

Kisspeptin is involved in ovarian follicular development during aging in rats

Fernandois¹,

Na²,

Cuevas³

et al. 2015

Journal of Endocrinology

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We have previously reported that kisspeptin (KP) may be under the control of the sympathetic innervation of the ovary. Considering that the sympathetic activity of the ovary increases with aging, it is possible that ovarian KP also increases during this period and participates in follicular development. To evaluate this possibility, we determined ovarian KP expression and its action on follicular development during reproductive aging in rats. We measured ovarian KP mRNA and protein levels in 6-, 8-, 10-and 12-month-old rats. To evaluate follicular developmental changes, intraovarian administration of KP or its antagonist, peptide 234 (P234), was performed using a mini-osmotic pump, and to evaluate FSH receptor (FSHR) changes in the senescent ovary, we stimulated cultured ovaries with KP, P234 and isoproterenol (ISO). Our results shows that KP expression in the ovary was increased in 10-and 12-month-old rats compared with 6-month-old rats, and this increase in KP was strongly correlated with the increase in ovarian norepinephrine observed with aging. The administration of KP produced an increase in corpora lutea and type III follicles in 6-and 10-month-old rats, which was reversed by P234 administration at 10 months. In addition, KP decreased the number and size of antral follicles in 6-and 10-month-old rats, while P234 administration produced an increase in these structures at the same ages. In ovarian cultures KP prevented the induction of FSHR by ISO. These results suggest that intraovarian KP negatively participates in the acquisition of FSHR, indicating a local role in the regulation of follicular development and ovulation during reproductive aging.

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Section: Introductionmentioning

confidence: 99%

Kisspeptin is involved in ovarian follicular development during aging in rats

Fernandois¹,

Na²,

Cuevas³

et al. 2015

Journal of Endocrinology

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“…To confirm the specificity of the antibodies, anti-Fos, -NKB and -kisspeptin antibodies were preabsorbed, respectively, with human Fos peptide (Oncogene Science, Cambridge, MA, USA), human NKB (Sigma-Aldrich, St. Louis, MO, USA), or sheep kisspeptin partial peptide, [Cys 37 ]sheep kisspeptin (37-53), which is a homologous peptide of [Cys 36 ]rat kisspeptin (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52), the immunogen generating the antibody [25]. Both were subjected to immunohistochemistry as mentioned above.…”

Section: Immunohistochemical Controlsmentioning

confidence: 99%

“…Third, axons, including kisspeptin, produce an extensive and intimate association with GnRH axon terminals at the median eminence in goats [16,37] and monkeys [38]. Recent electron microscopic observations have revealed that kisspeptin axons are closely associated with GnRH axons in goats [37] and rats [39]. Fourth, GnRH neurons express Kiss1r [10] but not NK3R [12] in sheep.…”

mentioning

confidence: 99%

Central Administration of Neurokinin B Activates Kisspeptin/NKB Neurons in the Arcuate Nucleus and Stimulates Luteinizing Hormone Secretion in Ewes During the Non-Breeding Season

et al. 2012

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Abstract. Human genetic studies have suggested that kisspeptin and neurokinin B (NKB) play pivotal roles in the control of gonadotropin-releasing hormone (GnRH) secretion. However, the role of NKB in this context is less clear compared with that of kisspeptin. In the present study, we investigated the ratio of colocalization of kisspeptin and NKB in neurons in the arcuate nucleus (ARC), the effects of intracerebroventricular infusion of NKB on luteinizing hormone (LH) secretion and whether the treatment activates ARC kisspeptin/NKB neurons in seasonally anestrous ewes. Double-labeling immunohistochemistry revealed that the majority of kisspeptin neurons coexpressed NKB in the ARC. Infusion of NKB for 2 h into the lateral ventricle elicited a discharge of LH, which resulted in significant increases in LH concentrations between 20 and 50 min after the start of infusion compared with a saline-infused control. Animals were sacrificed immediately after the end of infusion, and Fos expression in ARC kisspeptin neurons was immunohistochemically examined. The NKB treatment activated kisspeptin neurons throughout the ARC, and approximately 70% of kisspeptin neurons expressed Fos immunoreactivity at the caudal portion of the nucleus. The present study demonstrated that a central infusion of NKB elicited a discharge of LH, which was associated with the activation of a large population of ARC kisspeptin/NKB neurons in seasonally anestrous ewes. The results suggest that NKB plays a stimulatory role in the control of pulsatile GnRH secretion and that the population of ARC kisspeptin/NKB neurons is one of sites of the NKB action in sheep. Key words: Gonadotropin-releasing hormone, Kisspeptin, Neurokinin B, Seasonal anestrus, Sheep (J. Reprod. Dev. 58: [700][701][702][703][704][705][706] 2012) I nactivating mutations of not only Kiss1R, which encodes the kisspeptin receptor (GPR54), but also Tac3 and Tacr3, which encode neurokinin B (NKB) and its receptor (NK3R), respectively, produce gonadotropin deficiency and pubertal failure in humans [1][2][3][4]. These studies document that kisspeptin and NKB signaling play pivotal roles in the control of gonadotropin-releasing hormone (GnRH) secretion. Growing evidence indicates that kisspeptin acts as a potent stimulator of GnRH secretion in a variety of species [5], whereas the physiological role of NKB in this context is less clear.Human genetic studies [3,4] suggest that NKB would act to stimulate pulsatile GnRH/luteinizing hormone (LH) secretion.Indeed, it was demonstrated that a bolus intravenous (iv) injection of NKB or an agonist of NK3R, senktide, elicited a distinct LH discharge in castrated juvenile monkeys [6]. We also showed that a bolus intracerebroventricular (icv) administration of NKB induced a distinct LH pulse in ovariectomized (OVX) goats treated with estradiol (E2) and progesterone (P) [7]. However, in the goat study, the same treatment resulted in an overall reduction in LH secretion in the absence of gonadal steroids. A similar inhibitory effect of senktide was ...

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“…The studies performed on human autopsy samples recently have confirmed that kisspeptin neurons in humans are mainly located in the infundibular (arcuate in other species) and rostral preoptic area (POA) of the hypothalamus [24,29]. Studies have also indicated direct participation of kisspeptin in GnRH secretion [30], as evidenced by kisspeptin receptor mRNA expression by GnRH neurons [31,32], and close connections found between kisspeptin and GnRH neurons [22,24,26], although in humans not all GnRH neurons showed close connection with kisspeptin neurons [22,24,26,33].…”

Section: Functional Neuroanatomy Of the Kisspeptin Systemmentioning

confidence: 81%

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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Ultrastructural Evidence of Kisspeptin-Gonadotrophin-Releasing Hormone (GnRH) Interaction in the Median Eminence of Female Rats: Implication of Axo-Axonal Regulation of GnRH Release

Cited by 97 publications

References 47 publications

Kisspeptin is involved in ovarian follicular development during aging in rats

Kisspeptin is involved in ovarian follicular development during aging in rats

Central Administration of Neurokinin B Activates Kisspeptin/NKB Neurons in the Arcuate Nucleus and Stimulates Luteinizing Hormone Secretion in Ewes During the Non-Breeding Season

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

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