Abstract:
We tested the hypothesis that pulsatile GnRH stimulation of the pituitary
is required for normal gonadotropin secretion in humans. We administered
GnRH in pulsatile and continuous regimens in varying order to each of five
women with hypothalamic amenorrhea and presumed endogenous GnRH
deficiency. Mean serum levels of GnRH were similar during the pulsatile
and continuous regimens. All women ovulated during the pulsatile regimen
(progesterone, greater than 31.8 nmol/L (10 ng/mL); none ovulated during
the continuous regimen. Compared to pretreatment levels, FSH and
estradiol, as measured by RIA, and LH, as measured by bioassay, increased
significantly during the pulsatile GnRH regimen, but not during the
continuous regimen. However, LH and alpha-subunit, as measured by RIA,
increased significantly during both continuous and pulsatile GnRH
administration. We conclude that a pulsatile pattern of GnRH is essential
to normal functioning of the human female reproductive axis. Continuous
administration of GnRH, producing mean serum levels of the peptide
indistinguishable from those found during pulsatile administration,
stimulates some rise in a nonbioactive form of radioimmunoassayable
LH-like material and alpha-subunit, but does not stimulate bioactive LH,
FSH, estradiol, or progesterone and does not lead to ovulation.
