Interactions between Neurokinin B and kisspeptin in mediating estrogen feedback in healthy women

Karolina Skorupskaite, Jyothis T. George, Johannes D Veldhuis, Robert P. Millar, Richard A. Anderson

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 other participants: 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.

Original languageEnglish (US)
Pages (from-to)4628-4636
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume101
Issue number12
DOIs
StatePublished - Dec 1 2016

Fingerprint

Neurokinin B
Kisspeptins
Neurokinin-3 Receptors
Estradiol
Estrogens
Feedback
Gonadotropins
Transdermal Patch
Menstruation
Therapeutics
Gonadotropin-Releasing Hormone
Cross-Over Studies
Healthy Volunteers
Outcome Assessment (Health Care)
human KISS1 protein
Plasmas
Research

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Interactions between Neurokinin B and kisspeptin in mediating estrogen feedback in healthy women. / Skorupskaite, Karolina; George, Jyothis T.; Veldhuis, Johannes D; Millar, Robert P.; Anderson, Richard A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 101, No. 12, 01.12.2016, p. 4628-4636.

Research output: Contribution to journalArticle

Skorupskaite, Karolina ; George, Jyothis T. ; Veldhuis, Johannes D ; Millar, Robert P. ; Anderson, Richard A. / Interactions between Neurokinin B and kisspeptin in mediating estrogen feedback in healthy women. In: Journal of Clinical Endocrinology and Metabolism. 2016 ; Vol. 101, No. 12. pp. 4628-4636.
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