Unraveling the connection between GABA and kisspeptin in the control of reproduction

Giorgio, Noelia Paula Di; Bizzozzero-Hiriart, Marianne; Libertun, Carlos; Lux‐Lantos, Victoria

doi:10.1530/rep-18-0527

Cited by 18 publications

(13 citation statements)

References 78 publications

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“…Previous studies in camelids have reported this delay in animals treated with SP or NGF obtained from SP [53, 54] or when GnRH analogues are administered by intravaginal route [37]. The explanation for this delay in the LH peak is unclear, although Adams et al [55] suggested it could be the consequence of an unknown intermediate step in the ovulation pathway required for GnRH/LH release because the regulation of GnRH secretion in neurons depends on numerous inputs [56]. One of these inputs can be provided by interneurons such as kisspeptins and noradrenergic neurons after NGF interaction, as postulated by Carrasco et al [57].…”

Section: Discussionmentioning

confidence: 99%

Recombinant rabbit beta nerve growth factor production and its biological effects on sperm and ovulation in rabbits

et al. 2019

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In some induced-ovulating species, beta nerve growth factor (β-NGF) has important roles in ovulation, though data for rabbits are still inconclusive. In this study we first synthesized functional recombinant β-NGF from rabbit tissue (rrβ-NGF) to address the following objectives: 1) to compare rabbit β-NGF amino acid sequence with those of other induced- or spontaneous-ovulating species; 2) to assess the effects of rrβ-NGF on rabbit sperm viability and motility, and 3) to examine the in vivo ovulation inducing effect of rrβ-NGF added to the seminal dose in rabbit does. The NGF gene in rabbit prostate tissue was sequenced by Rapid Amplification of cDNA Ends and annotated in GenBank (KX528686). Recombinant rβ-NGF was produced in CHO cells and purified by affinity chromatography. Once confirmed by Western blotting and mass spectrometry (MALDI-TOF) that the amino acid sequence of the recombinant protein corresponded to β-NGF, its functionality was validated in PC12 cells in a successful dose-response study over 8 days. The amino acid sequence of prostate rabbit NGF differed to that of other species mainly in its receptor binding sites. In all the spontaneous ovulating species examined, compared with rabbit, alanine and proline residues, which interact with the high-affinity receptor, were replaced by a serine. In rabbits, asparagine and methionine were substituted by lysine at the low-affinity receptor binding site. In time- and dose-response experiments, the in vitro addition of rrβ-NGF to the ejaculate did not affect sperm viability whereas sperm motility parameters were enhanced by the addition of 1 μg/mL of the neuropeptide. Addition of this same concentration of rrβ-NGF to the seminal dose administered via the intravaginal route in does induced ovulation with a delayed LH peak, leading to a plasma progesterone increase, gestation and delivery. Our findings suggest that rrβ-NGF could be a useful option for biotechnological and reproduction assisted techniques in rabbits but further studies are needed.

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Section: Discussionmentioning

confidence: 99%

Recombinant rabbit beta nerve growth factor production and its biological effects on sperm and ovulation in rabbits

et al. 2019

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“…As the interaction between Kp and GABA is known from the literature [85,86], it also seemed possible that Kp-8 might directly affect GABA release in NAc. GABAergic neurons in the NAc have been shown to inhibit dopaminergic projections from the VTA [87].…”

Section: Discussionmentioning

confidence: 99%

Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in Rats

et al. 2021

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Kisspeptins (Kp) are RF-amide neuropeptide regulators of the reproductive axis that also influence anxiety, locomotion, and metabolism. We aimed to investigate the effects of intracerebroventricular Kp-8 (an N-terminally truncated octapeptide) treatment in Wistar rats. Elevated plus maze (EPM), computerized open field (OF), and marble burying (MB) tests were performed for the assessment of behavior. Serum LH and corticosterone levels were determined to assess kisspeptin1 receptor (Kiss1r) activation and hypothalamic-pituitary-adrenal axis (HPA) stimulation, respectively. GABA release from the nucleus accumbens (NAc) and dopamine release from the ventral tegmental area (VTA) and NAc were measured via ex vivo superfusion. Kp-8 decreased open arm time and entries in EPM, and also raised corticosterone concentration, pointing to an anxiogenic effect. Moreover, the decrease in arm entries in EPM, the delayed increase in immobility accompanied by reduced ambulatory activity in OF, and the reduction in interactions with marbles show that Kp-8 suppressed exploratory and spontaneous locomotion. The increase in GABA release from the NAc might be in the background of hypolocomotion by inhibiting the VTA-NAc dopaminergic circuitry. As Kp-8 raised LH concentration, it could activate Kiss1r and stimulate the reproductive axis. As Kiss1r is associated with hyperlocomotion, it is more likely that neuropeptide FF receptor activation is involved in the suppression of locomotor activity.

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“…Others believe that it will hyperpolarize GnRH neurons and inhibit GnRH secretion. In general, it mainly promotes the secretion of GnRH (52)(53)(54). Differences in the results may be related to the physiological stage of the body and the delay of GABA receptor signal transition.…”

Section: Related Research Work On Epilepsy and Pcosmentioning

confidence: 99%

Research Progress on the Effect of Epilepsy and Antiseizure Medications on PCOS Through HPO Axis

Zhang

Wei

et al. 2021

Front. Endocrinol.

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Epilepsy is a common chronic neurological disease that manifests as recurrent seizures. The incidence and prevalence of epilepsy in women are slightly lower than those in men. Polycystic ovary syndrome (PCOS), a reproductive endocrine system disease, is a complication that women with epilepsy are susceptible to, and its total prevalence is 8%–13% in the female population and sometimes as high as 26% in female epilepsy patients. The rate of PCOS increased markedly in female patients who chose valproate (VPA), to 1.95 times higher than that of other drugs. In addition, patients receiving other anti-seizure medications (ASMs), such as lamotrigine (LTG), oxcarbazepine (OXC), and carbamazepine (CBZ), also have reproductive endocrine abnormalities. Some scholars believe that the increase in incidence is related not only to epilepsy itself but also to ASMs. Epileptiform discharges can affect the activity of the pulse generator and then interfere with the reproductive endocrine system by breaking the balance of the hypothalamic–pituitary–ovarian (HPO) axis. ASMs may also cause PCOS-like disorders of the reproductive endocrine system through the HPO axis. Moreover, other factors such as hormone metabolism and related signalling pathways also play a role in it.

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Unraveling the connection between GABA and kisspeptin in the control of reproduction

Cited by 18 publications

References 78 publications

Recombinant rabbit beta nerve growth factor production and its biological effects on sperm and ovulation in rabbits

Recombinant rabbit beta nerve growth factor production and its biological effects on sperm and ovulation in rabbits

Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in Rats

Research Progress on the Effect of Epilepsy and Antiseizure Medications on PCOS Through HPO Axis

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