Mechanism of LH release after peripheral administration of kisspeptin in cattle.
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-bra...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0278564 |
| _version_ | 1797954054516637696 |
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| author | Carlos E P Leonardi Rodrigo A Carrasco Fernanda C F Dias Eric M Zwiefelhofer Gregg P Adams Jaswant Singh |
| author_facet | Carlos E P Leonardi Rodrigo A Carrasco Fernanda C F Dias Eric M Zwiefelhofer Gregg P Adams Jaswant Singh |
| author_sort | Carlos E P Leonardi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T23:11:34Z |
| format | Article |
| id | doaj.art-d2b07db273c14966bc8dba8ada5b14cc |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-10T23:11:34Z |
| publishDate | 2022-01-01 |
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| spelling | doaj.art-d2b07db273c14966bc8dba8ada5b14cc2023-01-13T05:31:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011712e027856410.1371/journal.pone.0278564Mechanism of LH release after peripheral administration of kisspeptin in cattle.Carlos E P LeonardiRodrigo A CarrascoFernanda C F DiasEric M ZwiefelhoferGregg P AdamsJaswant SinghKisspeptin 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.https://doi.org/10.1371/journal.pone.0278564 |
| spellingShingle | Carlos E P Leonardi Rodrigo A Carrasco Fernanda C F Dias Eric M Zwiefelhofer Gregg P Adams Jaswant Singh Mechanism of LH release after peripheral administration of kisspeptin in cattle. PLoS ONE |
| title | Mechanism of LH release after peripheral administration of kisspeptin in cattle. |
| title_full | Mechanism of LH release after peripheral administration of kisspeptin in cattle. |
| title_fullStr | Mechanism of LH release after peripheral administration of kisspeptin in cattle. |
| title_full_unstemmed | Mechanism of LH release after peripheral administration of kisspeptin in cattle. |
| title_short | Mechanism of LH release after peripheral administration of kisspeptin in cattle. |
| title_sort | mechanism of lh release after peripheral administration of kisspeptin in cattle |
| url | https://doi.org/10.1371/journal.pone.0278564 |
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