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Study · Animal study (in vivo) · rat · 2023

11 results

The interplay between kisspeptin and endocannabinoid systems modulates male hypothalamic and gonadic control of reproduction in vivo.

Marino M, D'Auria R, Mele E, Pastorino GMG, Di Pietro P, D'Angelo S, Della Rocca N, Operto FF, Vecchione C, Fasano S, Pierantoni R, Viggiano A, Meccariello R, Santoro A

Frontiers in endocrinology12 Oct 2023Cited by 7 (Europe PMC)

PMID37900144 (opens in a new tab)PMCIDPMC10602894 (opens in a new tab)DOI10.3389/fendo.2023.1269334 (opens in a new tab)PepBankPUB-37900144
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Summary

IntroductionMale reproduction is under the control of the hypothalamus-pituitary-gonadal (HPG) axis. The endocannabinoid system (ECS) and the kisspeptin system (KS) are two major signaling systems in the central and peripheral control of reproduction, but their possible interaction has been poorly investigated in mammals. This manuscript analyzes their possible reciprocal modulation in the control of the HPG axis.Materials and methodsAdolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A). The hypothalamic KS system and GnRH expression, circulating sex steroids and kisspeptin (Kiss1) levels, and intratesticular KS and ECS were evaluated by immunohistochemical and molecular methods. Non-coding RNAs (i.e., miR145-5p, miR-132-3p, let7a-5p, let7b-5p) were also considered.ResultsCirculating hormonal values were not significantly affected by Kp10 or AEA; in the hypothalamus, Kp10 significantly increased GnRH mRNA and aromatase Cyp19, Kiss1, and Kiss1 receptor (Kiss1R) proteins. By contrast, AEA treatment affected the hypothalamic KS at the protein levels, with opposite effects on the ligand and receptor, and SR141716A was capable of attenuating the AEA effects. Among the considered non-coding RNA, only the expression of miR145-5p was positively affected by AEA but not by Kp10 treatment. Localization of Kiss1+/Kiss1R+ neurons in the arcuate nucleus revealed an increase of Kiss1R-expressing neurons in Kp10- and AEA-treated animals associated with enlargement of the lateral ventricles in Kp10-treated animals. In the brain and testis, the selected non-coding RNA was differently modulated by Kp10 or AEA. Lastly, in the testis, AEA treatment affected the KS at the protein levels, whereas Kp10 affected the intragonadal levels of CB1 and FAAH, the main modulator of the AEA tone. Changes in pubertal transition-related miRNAs and the intratesticular distribution of Kiss1, Kiss1R, CB1, and CB2 following KP and AEA treatment corroborate the KS-ECS crosstalk also showing that the CB1 receptor is involved in this interplay.ConclusionFor the first time in mammals, we report the modulation of the KS in both the hypothalamus and testis by AEA and revealed the KP-dependent modulation of CB1 and FAAH in the testis. KP involvement in the progression of spermatogenesis is also suggested.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study11

11 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In adolescent male rats, circulating hormonal values were not significantly affected by Kp10.

    In plain wordsIn young male rats, kisspeptin‑10 did not significantly change hormone levels in the blood.

    Peptide
    Kisspeptin-10
    Outcome
    No significant changeCirculating hormonal values
    Study

    ratn: not reported in source

    adolescent male rats
    Outcome group
    Sex hormones and fertility · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Circulating hormonal values were not significantly affected by Kp10 or AEA; in the hypothalamus, Kp10 significantly increased GnRH mRNA and aromatase Cyp19, Kiss1, and Kiss1 receptor (Kiss1R) proteins.
    1 context sentence
    Summary · context
    Adolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A).
  2. 02AnimalAnimal study (in vivo)Mechanism

    In adolescent male rats, Kp10 significantly increased hypothalamic GnRH mRNA.

    In plain wordsIn young male rats, kisspeptin‑10 raised the brain's GnRH gene activity.

    Peptide
    Kisspeptin-10
    Outcome
    IncreaseHypothalamic GnRH mRNA
    Study

    ratn: not reported in source

    adolescent male rats
    Outcome group
    Sex hormones and fertility · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Circulating hormonal values were not significantly affected by Kp10 or AEA; in the hypothalamus, Kp10 significantly increased GnRH mRNA and aromatase Cyp19, Kiss1, and Kiss1 receptor (Kiss1R) proteins.
    1 context sentence
    Summary · context
    Adolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A).
  3. 03AnimalAnimal study (in vivo)Mechanism

    In adolescent male rats, Kp10 significantly increased hypothalamic aromatase Cyp19 protein.

    In plain wordsIn young male rats, kisspeptin‑10 raised the brain's level of the enzyme aromatase.

    Peptide
    Kisspeptin-10
    Outcome
    IncreaseHypothalamic aromatase Cyp19 protein
    Study

    ratn: not reported in source

    adolescent male rats
    Outcome group
    Sex hormones and fertility · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Circulating hormonal values were not significantly affected by Kp10 or AEA; in the hypothalamus, Kp10 significantly increased GnRH mRNA and aromatase Cyp19, Kiss1, and Kiss1 receptor (Kiss1R) proteins.
    1 context sentence
    Summary · context
    Adolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A).
  4. 04AnimalAnimal study (in vivo)Mechanism

    In adolescent male rats, Kp10 significantly increased hypothalamic Kiss1 protein.

    In plain wordsIn young male rats, kisspeptin‑10 raised the brain's level of Kiss1 protein.

    Peptide
    Kisspeptin-10
    Outcome
    IncreaseHypothalamic Kiss1 protein
    Study

    ratn: not reported in source

    adolescent male rats
    Outcome group
    Sex hormones and fertility · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Circulating hormonal values were not significantly affected by Kp10 or AEA; in the hypothalamus, Kp10 significantly increased GnRH mRNA and aromatase Cyp19, Kiss1, and Kiss1 receptor (Kiss1R) proteins.
    1 context sentence
    Summary · context
    Adolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A).
  5. 05AnimalAnimal study (in vivo)Mechanism

    In adolescent male rats, Kp10 significantly increased hypothalamic Kiss1 receptor (Kiss1R) protein.

    In plain wordsIn young male rats, kisspeptin‑10 raised the brain's level of the kisspeptin receptor.

    Peptide
    Kisspeptin-10
    Outcome
    IncreaseHypothalamic Kiss1 receptor protein
    Study

    ratn: not reported in source

    adolescent male rats
    Outcome group
    Sex hormones and fertility · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Circulating hormonal values were not significantly affected by Kp10 or AEA; in the hypothalamus, Kp10 significantly increased GnRH mRNA and aromatase Cyp19, Kiss1, and Kiss1 receptor (Kiss1R) proteins.
    1 context sentence
    Summary · context
    Adolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A).
  6. 06AnimalAnimal study (in vivo)Mechanism

    In adolescent male rats, Kp10 did not affect miR145-5p expression.

    In plain wordsIn young male rats, kisspeptin‑10 did not change the level of the small RNA miR145-5p.

    Peptide
    Kisspeptin-10
    Outcome
    No significant changemiR145-5p expression
    Study

    ratn: not reported in source

    adolescent male rats
    Outcome group
    Sex hormones and fertility · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Among the considered non-coding RNA, only the expression of miR145-5p was positively affected by AEA but not by Kp10 treatment.
    1 context sentence
    Summary · context
    Adolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A).
  7. 07AnimalAnimal study (in vivo)Mechanism

    In adolescent male rats, Kp10 treatment increased Kiss1R-expressing neurons in the arcuate nucleus.

    In plain wordsIn young male rats, kisspeptin‑10 raised the number of brain cells that carry the kisspeptin receptor.

    Peptide
    Kisspeptin-10
    Outcome
    IncreaseKiss1R-expressing neurons in the arcuate nucleus
    Study

    ratn: not reported in source

    adolescent male rats
    Outcome group
    Sex hormones and fertility · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Localization of Kiss1+/Kiss1R+ neurons in the arcuate nucleus revealed an increase of Kiss1R-expressing neurons in Kp10- and AEA-treated animals associated with enlargement of the lateral ventricles in Kp10-treated animals.
    1 context sentence
    Summary · context
    Adolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A).
  8. 08AnimalAnimal study (in vivo)Safety outcome

    In adolescent male rats, Kp10 treatment was associated with enlargement of the lateral ventricles.

    In plain wordsIn young male rats, kisspeptin‑10 was linked to larger fluid spaces in the brain.

    Peptide
    Kisspeptin-10
    Outcome
    IncreaseLateral ventricle size
    Study

    ratn: not reported in source

    adolescent male rats
    Outcome group
    Adverse events · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Localization of Kiss1+/Kiss1R+ neurons in the arcuate nucleus revealed an increase of Kiss1R-expressing neurons in Kp10- and AEA-treated animals associated with enlargement of the lateral ventricles in Kp10-treated animals.
    1 context sentence
    Summary · context
    Adolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A).
  9. 09AnimalAnimal study (in vivo)Mechanism

    In adolescent male rats, the selected non-coding RNAs in brain and testis were differently modulated by Kp10.

    In plain wordsIn young male rats, kisspeptin‑10 changed some small RNAs in the brain and testis in different ways.

    Peptide
    Kisspeptin-10
    Outcome
    MixedNon-coding RNA expression in brain and testis
    Study

    ratn: not reported in source

    adolescent male rats
    Outcome group
    Sex hormones and fertility · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In the brain and testis, the selected non-coding RNA was differently modulated by Kp10 or AEA.
    1 context sentence
    Summary · context
    Adolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A).
  10. 10AnimalAnimal study (in vivo)Mechanism

    In adolescent male rats, Kp10 affected the intragonadal level of CB1 in the testis; the direction is not stated.

    In plain wordsIn young male rats, kisspeptin‑10 changed the amount of the CB1 receptor in the testis.

    Peptide
    Kisspeptin-10
    Outcome
    Direction not reportedIntratesticular CB1 level
    Study

    ratn: not reported in source

    adolescent male rats
    Outcome group
    Sex hormones and fertility · Reproductive and sexual health
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Lastly, in the testis, AEA treatment affected the KS at the protein levels, whereas Kp10 affected the intragonadal levels of CB1 and FAAH, the main modulator of the AEA tone.
    1 context sentence
    Summary · context
    Adolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A).
  11. 11AnimalAnimal study (in vivo)Mechanism

    In adolescent male rats, Kp10 affected the intragonadal level of FAAH in the testis; the direction is not stated.

    In plain wordsIn young male rats, kisspeptin‑10 changed the amount of the enzyme FAAH in the testis.

    Peptide
    Kisspeptin-10
    Outcome
    Direction not reportedIntratesticular FAAH level
    Study

    ratn: not reported in source

    adolescent male rats
    Outcome group
    Sex hormones and fertility · Reproductive and sexual health
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Lastly, in the testis, AEA treatment affected the KS at the protein levels, whereas Kp10 affected the intragonadal levels of CB1 and FAAH, the main modulator of the AEA tone.
    1 context sentence
    Summary · context
    Adolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A).

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    10 Oct 2026, 09:43 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

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