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Influence of neurokinin b, dynorphin a and kisspeptin-10 on in vitro gonadotropin secretion by anterior pituitary cells isolated from pubescent ewes
Szysiak N, Kosior-Korzecka U, longo V, Patkowski K, Greguła-Kania M, Nowakiewicz A, Bochniarz M,Junkuszew A (2025) Influence of neurokinin b, dynorphin a and kisspeptin-10 on in vitro gonadotropin secretion by anterior pituitary cells isolated from pubescent ewes. J Vet Res doi: 10.2478/jvetres-2025-0003
Objective: The aim of the study was to analyze the direct effect of the hypothalamic neuropeptides kisspeptin-10, neurokinin B, and dynorphin A on gonadotropin secretion by pituitary cells isolated from pubescent ewes.
Summary: Puberty is a multifactorial and complex process in animal development and in the case of livestock, timely attainment of sexual maturity contributes to increased reproductive efficiency, which leads to higher profitability. Studies revealed that kisspeptin, neurokinin B and dynorphin neuropeptides, collectively referred to as KNDy neuropeptides, are recognized as the key neuropeptides produced and secreted by the arcuate nucleus of the hypothalamus (ARC), and involved in the endocrine regulation of the onset of puberty. They all play roles in the endocrine regulation of the hypothalamic-pituitary-ovarian (HPO) axis in puberty. Kisspeptin-10, NKB and Dyn A had a direct impact on gonadotropin secretion by ovine pituitary cells. However, a detailed explanation of their role in gonadotropin secretion by the anterior pituitary gland in sheep and their impact on the regulation of the HPO axis during sexual maturation or in the pathomechanism of delayed puberty requires further studies.
Usage: Prepubertal ewes received 1 μL (0.7 μg) of NKB-SAP (NK3-SAP) [IT-63] or Blank-SAP (IT-21) injections aimed at the arcuate (ARC) nucleus to ablate neurons expressing NK3R.
Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)
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The effect of NK3-Saporin injection within the arcuate nucleus on puberty, the LH surge, and the response to Senktide in female sheep
Aerts EG, Griesgraber MJ, Shuping SL, Bowdridge EC, Hardy SL, Goodman RL, Nestor CC, Hileman SM (2024) The effect of NK3-Saporin injection within the arcuate nucleus on puberty, the LH surge, and the response to Senktide in female sheep. Biol Reprod 110(2):275-287. doi: 10.1093/biolre/ioad147 PMID: 37930247
Objective: To investigate the role of NKB-SAP (NK3-SAP) in the arcuate nucleus on the timing of puberty, the LH surge, and the response to the NK3R agonist senktide in female sheep.
Summary: This study explores how the ablation of NK3R-containing neurons in the arcuate nucleus affects puberty onset and reproductive hormone dynamics in female sheep. The findings demonstrate that NK3-SAP injections significantly delay puberty, reduce the amplitude of the LH surge, and alter the response to senktide, underscoring the critical role of NK3R-containing neurons in reproductive function.
Usage: Prepubertal ewes received 1 μL (0.7 μg) of NKB-SAP (NK3-SAP) [IT-63] or Blank-SAP (IT-21) injections aimed at the arcuate (ARC) nucleus to ablate neurons expressing NK3R.
Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)
New methods to investigate the GnRH pulse generator
Ivanova D, O’Byrne KT (2024) New methods to investigate the GnRH pulse generator. J Mol Endocrinol 72(2):e230079. doi: 10.1530/JME-23-0079 PMID: 38085702
Objective: To review the latest methodologies and insights into the GnRH pulse generator and its role in regulating reproductive hormone secretion.
Summary: The paper discusses recent advancements in understanding the GnRH pulse generator and its role in reproductive hormone secretion. It highlights the involvement of kisspeptin/neurokinin B/dynorphin (KNDy) neurons and the use of advanced techniques like genetic mouse models, electrophysiology, optogenetics, and calcium imaging. These findings enhance our comprehension of the KNDy network’s oscillatory behavior and its regulation by gonadal steroids, which is crucial for developing better infertility treatments.
Related Products: NKB-SAP (Cat. #IT-63)
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Partial loss of KNDy neurons in prenatally androgen treated female rats alters the LH secretion and ovarian morphology in a model of polycystic ovary syndrome
Aquino NSS, Campideli-Santana AC, Antunes LM, Araújo-Lopes R, da Costa Silva KS, Costa Henriques P, de Oliveira Gusmão D, Bernuci MP, Szawka RE, dos Reis AM (2023) Partial loss of KNDy neurons in prenatally androgen treated female rats alters the LH secretion and ovarian morphology in a model of polycystic ovary syndrome. J Endocrine Society 7(S1):bvad114.1215. doi: 10.1210/jendso/bvad114.1215
Objective: To examine the impact of partial loss of KNDy neurons in prenatally androgen-treated female rats on luteinizing hormone (LH) secretion and ovarian morphology, as a model of polycystic ovary syndrome (PCOS).
Summary: The study found that the ablation of KNDy neurons resulted in increased LH pulse amplitude and mean LH levels without affecting pulse frequency, and partially restored the number of primordial follicles, suggesting KNDy neurons’ role in modulating LH release and ovarian reserve in PCOS.
Usage: Intra-ARC stereotaxic injections of the neurokinin-3 receptor agonist conjugated with Saporin (NKB-SAP, IT-63) to induce the lesion of KNDy neurons. Blank-SAP (IT-21) was used as a control.
Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)
Submaximal loss of KNDy neurons accelerates and amplifies pulsatile LH secretion in female rats
Campideli-Santana AC, da Costa Silva KS, Araújo-Lopes R, Antunes LM, Szawka RE (2023) Submaximal loss of KNDy neurons accelerates and amplifies pulsatile LH secretion in female rats. J Endocrine Society 7(S1):bvad114.1214. doi: 10.1210/jendso/bvad114.1214
Objective: To investigate the impact of the submaximal loss of KNDy neurons on the pulsatile secretion of luteinizing hormone (LH) in female rats.
Summary: The study found that a partial loss of these neurons led to irregular estrous cycles and increased frequency and amplitude of LH pulses. This suggests a new role for KNDy neurons in moderating LH pulse frequency and amplitude in ovary-intact animals, with implications for early antral follicle recruitment.
Usage: Adult female rats underwent a neurochemical ablation of KNDy neurons via intra-ARC stereotaxic injections of NKB-SAP (IT-63), while control animals received Blank-SAP (IT-21).
Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)
Lesions of kndy and kiss1r neurons in the arcuate nucleus produce different effects on lh pulse patterns in female sheep
Goodman RL, Moore AM, Onslow K, Hileman SM, Hardy SL, Bowdridge EC, Walters BA, Agus S, Griesgraber MJ, Aerts EG, Lehman MN, Coolen LM (2023) Lesions of kndy and kiss1r neurons in the arcuate nucleus produce different effects on lh pulse patterns in female sheep. Endocrinology 164(11):bqad148. doi: 10.1210/endocr/bqad148 PMID: 37776515
Objective: To test the functional role of ovine KNDy neurons in pulse generation and identify the roles of nearby Kiss1 receptor (Kiss1R)-containing cells.
Summary: Injection of NK3-SAP (NKB-SAP) ablated over 90% of the KNDy cells, Kiss-SAP lesioned about two-thirds of the Kiss1R population. This led to a significant decrease in LH pulse amplitude and altering LH pulse patterns. NK3-SAP increased the interpulse interval without affecting the regularity of LH pulses, whereas Kiss-SAP disrupted their regular hourly occurrence but not the interpulse interval. The findings suggest that KNDy neurons are critical for GnRH pulse generation in ewes, while ARC Kiss1R cells support the amplitude and regularity of these pulses, possibly as part of a positive feedback loop involving GABA or glutamate.
Usage: Saporin conjugates were injected into the arcuate nucleus. Kiss-SAP (kisspeptin54-SAP) was diluted to 700 ng/μL in PBS immediately before use. In preliminary work to test the effectiveness of Kiss-SAP, a single unilateral injection (1 μL of 700 ng/μL) of this conjugate was made in the preoptic area of 3 ewes. The contralateral side was used as control and either received no injections or Blank-SAP (1 μL of 700 ng/μL) (IT-21).
Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)
KNDy neurons as the GnRH pulse generator: Recent studies in ruminants
Nestor CC, Merkley CM, Lehman MN, Hileman SM, Goodman RL (2023) KNDy neurons as the GnRH pulse generator: Recent studies in ruminants. Peptides 164:171005. doi: 10.1016/j.peptides.2023.171005 PMID: 36990389
Objective: This publication aims to summarize and provide an overview of recent studies investigating the role of KNDy neurons as the pulse generator for gonadotropin-releasing hormone (GnRH) release in ruminants.
Summary: Recent studies in ruminants, specifically sheep and cows, have investigated the role of KNDy neurons in driving the pulsatile release of GnRH. These studies have demonstrated the rhythmic electrical activity of KNDy neurons, coinciding with the pulsatile secretion of GnRH in ewes, suggesting their central role as the pulse generator. Additionally, the expression patterns of genes related to KNDy neurons and GnRH pulsatility have been examined in cows, revealing variations throughout the estrous cycle and indicating a potential involvement of KNDy neurons in regulating GnRH release in this species. These findings contribute to our understanding of reproductive physiology in ruminants and have implications for both animal and human reproductive health.
Related Products: NKB-SAP (Cat. #IT-63)
Evidence that the LH surge in ewes involves both neurokinin B–dependent and –independent actions of kisspeptin.
Goodman RL, He W, Lopez JA, Bedenbaugh MN, McCosh RB, Bowdridge EC, Coolen LM, Lehman MN, Hileman SM (2019) Evidence that the LH surge in ewes involves both neurokinin B–dependent and –independent actions of kisspeptin. Endocrinology 160(12):2990-3000. doi: 10.1210/en.2019-00597
Objective: To determine if NKB is involved in the RCh of the ewe in the LH surge.
Summary: NKB signaling in the RCh increases kisspeptin levels critical for the full amplitude of the LH surge in the ewe, but kisspeptin release occurs independently of retrochiamatic area (RCh) input at the onset of the surge to initiate GnRH secretion.
Usage: Bilaterial injections in the RCh of either NK3-SAP or Blank-SAP.
Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)
Selective role of neurokinin B in IL-31–induced itch response in mice.
Sakata D, Uruno T, Matsubara K, Andoh T, Yamamura K, Magoshi Y, Kunimura K, Kamikaseda Y, Furue M, Fukui Y (2019) Selective role of neurokinin B in IL-31–induced itch response in mice. J Allergy Clin Immunol 144(4):1130-1133. doi: 10.1016/j.jaci.2019.06.031
Objective: To examine the physiological significance of neurokinin B in IL-31–induced itch sensation.
Summary: IL-31–induced scratching was unaffected by intrathecal injection of Nppb-SAP. In contrast,treatment with Bombesin-SAP reduced IL-31–induced scratching. Neurokinin B acts upstream of GRP to transmit IL-31–induced itch sensation.
Usage: Intrathecal injection
Related Products: Bombesin-SAP (Cat. #IT-40), Nppb-SAP (Cat. #IT-69), Blank-SAP (Cat. #IT-21), NKB-SAP (Cat. #IT-63)
Glutamatergic neurokinin 3 receptor neurons in the median preoptic nucleus modulate heat-defense pathways in female mice.
Krajewski-Hall SJ, Miranda Dos Santos F, McMullen NT, Blackmore EM, Rance NE (2019) Glutamatergic neurokinin 3 receptor neurons in the median preoptic nucleus modulate heat-defense pathways in female mice. Endocrinology 160(4):803-816. doi: 10.1210/en.2018-00934
Objective: To characterize the thermoregulatory role of MnPO NK3R neurons in female mice.
Summary: Study suggests that KNDy neurons modulate thermosensory pathways for heat defense indirectly via a subpopulation of glutamatergic MnPO neurons that express NK3R.
Usage: Mice were bilaterally injected with 10 ng NK3-SAP in 100 nL PBS (n = 14) or blank-SAP (n = 8) in the preoptic area adjacent to the MnPO.
Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)