Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 101, Issue 12, Pages 4628-4636Publisher
ENDOCRINE SOC
DOI: 10.1210/jc.2016-2132
Keywords
-
Categories
Funding
- Wellcome Trust through Scottish Translational Medicine and Therapeutics Initiative Grant [102419/Z/13/A]
- Medical Research Council [G0701682]
- Wellcome Trust [102419/Z/13/A] Funding Source: Wellcome Trust
Ask authors/readers for more resources
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 trans-dermal 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 mu g/d) were applied after 5 days of NK3R antagonist treatment. At 24-hour estradiol treatment, women were randomized to 7-hour kisspeptin-10 (4 mu g/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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available