Context: Neurokinin B (NKB) is obligate for human puberty, but its role in adult female gonadotropin secretion and ovarian follicle growth is unknown.
Objective: To investigate antagonism of NKB on pulsatile GnRH/LH secretion and ovarian follicle development in normal women.
Design: Open investigation of the effects of a neurokinin-3 receptor antagonist (NK3Ra) vs no treatment control cycle.
Setting: Clinical Research Facility.
Patients or other participants: Healthy women with regular menses (n=13).
Intervention(s): NK3R antagonist MLE4901 40 mg bd oral was taken from cycle day 5-6 for 7 days.
Main outcome measure(s): LH secretion, ovarian follicle growth and timing of ovulation.
Results: NK3Ra administration reduced basal LH secretion without a change in pulse frequency and delayed the LH surge by 7 days, the duration of treatment (cycle day: 22±1 vs 15±1 in control cycles, p=0.0006). Follicle growth (diameter at the end of administration of NK3R antagonist administration: 9.3±0.4 vs 15.1±0.9 mm in controls, p<0.0001) and rising estradiol concentrations (166±29 vs 446±86 pmol/l in controls, p<0.0001) were prevented. After treatment follicle development resumed and normal pre-ovulatory follicle diameter and estradiol concentrations were demonstrated. Post-ovulatory progesterone rise was similarly delayed (peak cycle day: 30±2 vs 22±1, p=0.002) and cycle length was prolonged (35±1 vs 29±1 days in controls, p=0.0003) but luteal progesterone excretion was unaffected by the NK3Ra (LH surge day +7 urinary progesterone 58±10 vs 48±7 pmol/mol creatinine in controls, ns).
Conclusions: These data demonstrate the involvement of NKB-NK3R signalling in the physiological regulation of GnRH/LH secretion, determining normal follicle development in women.
- Journal Article