Interactions Between Neurokinin B and Kisspeptin in Mediating Estrogen Feedback in Healthy Women.
J Clin Endocrinol Metab
; 101(12): 4628-4636, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27636018
ABSTRACT
CONTEXT Kisspeptin and neurokinin B (NKB) are obligate for normal gonadotropin secretion, but their hierarchy is unexplored in normal women. OBJECTIVE:
To investigate the interaction between kisspeptin and NKB on estrogen-regulated LH secretion.DESIGN:
Women were treated with neurokinin-3 receptor (NK3R) antagonist followed by transdermal estradiol to induce LH secretion 48 hours later, with kisspeptin-10 or vehicle infusion during estrogen administration in a 2-way crossover study.SETTING:
Clinical research facility. PATIENTS OR OTHERPARTICIPANTS:
Healthy females with regular menses. INTERVENTION(S) NK3R antagonist AZD4901 40 mg twice daily orally was taken from cycle day 4-6 for 6 days (n = 10, with 10 no treatment controls). Transdermal estradiol patches (200 µg/d) were applied after 5 days of NK3R antagonist treatment. At 24-hour estradiol treatment, women were randomized to 7-hour kisspeptin-10 (4 µg/kg/h) or vehicle iv infusion, with the alternate infusion in a subsequent cycle. MAIN OUTCOME MEASURE(S) Plasma gonadotropin and estradiol secretion.RESULTS:
After an initial suppression, LH secretion was increased 48 hours after estradiol treatment. Kisspeptin-10 increased LH secretion during the inhibitory phase, and LH remained elevated beyond the discontinuation of kisspeptin-10 infusion. NK3R antagonist decreased LH pulse frequency (0.5 ± 0.2 vs 0.7 ± 0.2 pulses/h, P < .05) and stimulated FSH response to kisspeptin-10 infusion (10.7 ± 11.0 vs 5.0 ± 3.6 IU/L, P < .05) with a nonsignificant rise in LH. The duration of LH response was blunted, with LH being lower at 48 hours (7.5 ± 4.8 vs 15.0 ± 11.4 IU/L, P < .05).CONCLUSIONS:
These data demonstrate that NKB signaling regulates GnRH/LH secretion in normal women, and is predominantly proximal to kisspeptin in mediating estrogenic positive and negative feedback on LH secretion.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hormônio Luteinizante
/
Neurocinina B
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Transdução de Sinais
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Receptores de Taquicininas
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Neurotransmissores
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Retroalimentação Fisiológica
/
Estradiol
/
Estrogênios
/
Kisspeptinas
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
/
Adult
/
Female
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Humans
/
Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2016
Tipo de documento:
Article