Gonadotropin Dynamics in Patients with Gonadal Dysgenesis: A Model for the Study of Gonadotropin Regulation

Abstract

In 19 patients with gonadal dysgenesis, 12–35 yr of age, a disproportionally greater elevation of serum FSH (10 times) than LH (2–3 times) was found when compared with the values observed in premenopausal women. The mean serum LH concentration, but not mean serum FSH concentration, was significantly lower than those found in postmenopausal women. The elevated levels of serum LH and FSH in these patients are maintained by periodic pulsatile pituitary discharges with an average frequency of 90 min. Coincidental pulses of LH and FSH of comparable magnitude are discernible, but obvious dissimilarities in the pattern are apparent. E2 infusion (50 μg/hr × 4 hr) abolished the pulsatile nature of LH release and to a lesser degree FSH release which resulted in a rapid reduction in circulating gonadotropin concentrations. Despite the rapid disappearance of circulating E2 following the infusion, the suppression was sustained for an average of 6 hr. The pattern of recovery was composed of an abrupt resumption of pulsatile discharges of larger magnitude than those observed during control periods. This was more apparent for LH than for FSH which resulted in a reduction of FSH/LH ratio. During a period of sustained suppression by ethinyl estradiol, a concomitant release of LH and FSH in response to im progesterone and estradiol benzoate administration was observed. These data indicate that the unrestrained hypothalamicpituitary system in patients with gonadal dysgenesis is responsive to both negative and positive feedback action of estradiol and that estradiol is a major gonadal steroid in the regulation of tonic gonadotropin secretion via modulation of the amplitude of the pulsatile discharges.