Mechanism of LH release after peripheral administration of kisspeptin in cattle.

Leonardi CEP, Carrasco RA, Dias FCF, Zwiefelhofer EM, Adams GP, Singh J

PloS one2 Dec 2022Cited by 5 (Europe PMC)

PMID36459509PMCIDPMC9718405DOI10.1371/journal.pone.0278564PepBankPUB-36459509

Summary

Kisspeptin modulates GnRH secretion in mammals and peripheral administration of 10-amino acid fragment of kisspeptin (Kp10) induces LH release and ovulation in cattle. Experiments were done to determine if iv administration of kisspeptin will activate GnRH neurons (i.e., after crossing the blood-brain barrier) and if pre-treatment with a GnRH receptor blocker will alter kisspeptin-induced LH release (from gonadotrophs) and ovulation. In Experiment 1, cows (n = 3 per group) were given human-Kisspeptin10 (hKp10; 3 x 15 mg iv at 60-min intervals) or normal saline and euthanized 150 min after treatment was initiated. Every 20th free-floating section (50 μm thickness) from the preoptic area to hypothalamus was double immunostained to colocalize GnRH- (DAB) and activated neurons (cFOS; Nickel-DAB). Kisspeptin induced plasma LH release from 15 to 150 min (P = 0.01) but the proportion of activated GnRH neurons did not differ between groups (5.8% and 3.5%, respectively; P = 0.11). Immunogold electron microscopy detected close contacts between kisspeptin fibers and GnRH terminals in the median eminence. In Experiment 2, pubertal heifers (n = 5 per group) were treated with 1) hKp10 iv, 2) Cetrorelix (GnRH antagonist; im) + hKp10 iv or 3) saline on Day 6 of the follicular wave under low-progesterone condition. A rise in plasma LH concentration was detected from 15 to 240 min in the hKp10 group but not in cetrorelix or control group (P<0.001). Ovulations were detected only in the hKp10 group (4/5; P = 0.02). Cetrorelix treatment was associated with regression of the preovulatory dominant follicle and emergence of a new follicular wave 3.4±0.75 days after the treatment in all five heifers. Results support the hypothesis that the effect of peripheral kisspeptin is mediated downstream of GnRH synthesis and does not involve GnRH-independent LH release from gonadotrophs. Peripheral kisspeptin may release pre-synthesized GnRH from the nerve terminals in areas outside the blood-brain barrier.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

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

01AnimalAnimal study (in vivo)Efficacy outcome
In pubertal heifers, intravenous hKp10 raised plasma LH from 15 to 240 min, compared with the control group.
In plain wordsIn heifers, kisspeptin‑10 given into a vein raised blood LH compared with saline.
Peptide
Kisspeptin-10
Outcome
IncreasePlasma LH concentration after hKp10 (Experiment 2)
Study
cattlen = 15
Comparator
Saline
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Studied dose
Dose not stated · intravenousAs given in this study (cattle).
Source sentences
Summary
A rise in plasma LH concentration was detected from 15 to 240 min in the hKp10 group but not in cetrorelix or control group (P<0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In Experiment 2, pubertal heifers (n = 5 per group) were treated with 1) hKp10 iv, 2) Cetrorelix (GnRH antagonist; im) + hKp10 iv or 3) saline on Day 6 of the follicular wave under low-progesterone condition.
Show in the study text Report a problemFND-3645950904
02AnimalAnimal study (in vivo)Efficacy outcome
In pubertal heifers, ovulations were detected only in the hKp10 group.
In plain wordsIn heifers, ovulation occurred only in the group that received kisspeptin‑10.
Peptide
Kisspeptin-10
Outcome
IncreaseOvulation after hKp10 (Experiment 2)
Study
cattlen = 15
Comparator
Saline
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Studied dose
Dose not stated · intravenousAs given in this study (cattle).
Source sentences
Summary
Ovulations were detected only in the hKp10 group (4/5; P = 0.02).
1 context sentence(design, population, supporting numbers)
Summary · context
In Experiment 2, pubertal heifers (n = 5 per group) were treated with 1) hKp10 iv, 2) Cetrorelix (GnRH antagonist; im) + hKp10 iv or 3) saline on Day 6 of the follicular wave under low-progesterone condition.
Show in the study text Report a problemFND-3645950906
03AnimalAnimal study (in vivo)Efficacy outcome
In cows, intravenous human kisspeptin‑10 induced plasma LH release from 15 to 150 min compared with saline.
In plain wordsIn cows, kisspeptin‑10 given into a vein raised blood LH compared with saline.
Peptide
Kisspeptin-10
Outcome
IncreasePlasma LH release after hKp10 (Experiment 1)
Study
cattlen = 6
Comparator
Saline
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Studied dose
3 x 15 mg · intravenousAs given in this study (cattle).
Source sentences
Summary
Kisspeptin induced plasma LH release from 15 to 150 min (P = 0.01)
1 context sentence(design, population, supporting numbers)
Summary · context
In Experiment 1, cows (n = 3 per group) were given human-Kisspeptin10 (hKp10; 3 x 15 mg iv at 60-min intervals) or normal saline and euthanized 150 min after treatment was initiated.
Show in the study text Report a problemFND-3645950901
04AnimalAnimal study (in vivo)Mechanism
In cows, the proportion of activated GnRH neurons did not differ between kisspeptin‑10 and saline groups.
In plain wordsIn cows, kisspeptin‑10 did not change the share of activated GnRH neurons compared with saline.
Peptide
Kisspeptin-10
Outcome
No significant changeProportion of activated GnRH neurons (Experiment 1)
Study
cattlen = 6
Comparator
Saline
Outcome group
Receptor activity and mechanism · Reproductive and sexual health
Studied dose
3 x 15 mg · intravenousAs given in this study (cattle).
Measurements
Activated GnRH neurons
5.8%
kisspeptin
Activated GnRH neurons
3.5%
saline
Source sentences
Summary
the proportion of activated GnRH neurons did not differ between groups (5.8% and 3.5%, respectively; P = 0.11).
1 context sentence(design, population, supporting numbers)
Summary · context
In Experiment 1, cows (n = 3 per group) were given human-Kisspeptin10 (hKp10; 3 x 15 mg iv at 60-min intervals) or normal saline and euthanized 150 min after treatment was initiated.
Show in the study text Report a problemFND-3645950902

Natural levels measured1

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

05AnimalEndogenous levelAnimal study (in vivo)Mechanism
In cows, immunogold electron microscopy detected close contacts between kisspeptin fibers and GnRH terminals in the median eminence.
In plain wordsIn cows, the body's own kisspeptin fibres were found in close contact with GnRH nerve endings.
Peptide
Kisspeptin-10
Outcome
Not applicableContacts between kisspeptin fibers and GnRH terminals in the median eminence
Study
cattlen: not reported in source
Outcome group
Receptor activity and mechanism · Reproductive and sexual health
Source sentences
Summary
Immunogold electron microscopy detected close contacts between kisspeptin fibers and GnRH terminals in the median eminence.
1 context sentence(design, population, supporting numbers)
Summary · context
In Experiment 1, cows (n = 3 per group) were given human-Kisspeptin10 (hKp10; 3 x 15 mg iv at 60-min intervals) or normal saline and euthanized 150 min after treatment was initiated.
This result measures the body's own Kisspeptin-10. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3645950903

Studies that did not test the peptide alone1

In this study, Kisspeptin-10 was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Kisspeptin-10.

06AnimalNot a test of Kisspeptin-10 aloneAnimal study (in vivo)Efficacy outcome
In pubertal heifers, cetrorelix (a GnRH antagonist) plus hKp10 produced no rise in plasma LH. The regimen has two active drugs.
In plain wordsIn heifers, kisspeptin‑10 together with the GnRH blocker cetrorelix did not raise blood LH.
Peptide
Kisspeptin-10
Outcome
No significant changePlasma LH after cetrorelix plus hKp10 (Experiment 2)
Study
cattlen = 15
Comparator
Saline
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Source sentences
Summary
A rise in plasma LH concentration was detected from 15 to 240 min in the hKp10 group but not in cetrorelix or control group (P<0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
In Experiment 2, pubertal heifers (n = 5 per group) were treated with 1) hKp10 iv, 2) Cetrorelix (GnRH antagonist; im) + hKp10 iv or 3) saline on Day 6 of the follicular wave under low-progesterone condition.
In this study, Kisspeptin-10 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Kisspeptin-10.
Show in the study text Report a problemFND-3645950905

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.

Version 3Current
27 Oct 2026, 16:35 UTC
Study data updated · source update from Europe PMC
Version 2
10 Oct 2026, 09:43 UTC
Study results updated
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC