C. B. Lambalk

Short-Term Pituitary Desensitization to LH-RH after Pulsatile LH-RH in the Ovariectomized Rat: An in vivo Experiment

The development of acute insensitivity of pituitary LH secretion to LH-RH after a short exposure to LH-RH is described. In the first experiment, ovariectomized (OVX), phenobarbital-pretreated rats were given pulses of LH-RH (1.25 or 6.25 ng/100 g body weight (b.w.), intravenously). In rats given 1.25 ng at time 0, 6.25 ng at 60 min, 1.25 ng at 80 min and 1.25 ng at 120 min, there was a substantial increase in plasma LH after the first two injections, no increase after the third injection and a relatively small increase after the fourth one. In other rats treated identically but not given a 1.25-ng dose at 80 min, the plasma LH rise in response to the 1.25-ng dose at 120 min was comparable to that seen after the 1.25-ng dose given at time 0. If the 1.25-ng LH-RH pulses given at times 0 and 80 min were replaced by a rat pituitary extract, the plasma LH rise in response to the 1.25-ng dose at 120 min was comparable to that seen after administration of pituitary extract. In the second experiment, OVX phenobarbital-pretreated rats were given 1.25 ng LH-RH/100 g b.w. at t = 0. They were then divided into three groups, each receiving 1.25, 3.75 or 6.25 ng LH-RH/100 g b.w. at t = 60 min. Each of these three groups was again divided into three groups which received 1.25 ng LH-RH/100 g b.w. at 80, 100 or 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)

The frequency of pulsatile luteinizing hormone-releasing hormone treatment and luteinizing hormone and follicle-stimulating hormone secretion in women with amenorrhea of suprapituitary origin * †

The influence of luteinizing hormone-releasing hormone (LH-RH) pulse frequency on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was studied in hypogonadotropic hypogonadal women. They received three regimens of 5 days of pulsatile LH-RH (5 micrograms/pulse) given at 30-, 90-, or 180-minute intervals, with at least 6 weeks between treatments. On day 1, LH and FSH increased in proportion to the LH-RH pulse frequency. After 5 days of treatment with the 30- and 90-minute intervals, LH was still elevated, but FSH had returned to pretreatment levels together with a decline of the FSH response. The LH response only declined during treatment with the 30-minute pulse interval. During each treatment, estradiol (E2) increased. Explanations for dissociation between LH and FSH secretion during treatment with higher LH-RH pulse frequencies could be: (1) desensitization of FSH rather than LH secretion on LH-RH; (2) a differential effect of E2 on LH and FSH; (3) nonsteroidal ovarian factors selectively regulating LH and/or FSH release.

Pulsatile LH-RH treatment induces a relatively low response of LH and FSH, while discontinuation enhances the response in women with amenorrhea of suprapituitary origin

Five women with amenorrhea of suprapituitary origin were given intravenous injections of 10 micrograms LH-RH every 90 minutes for 4 days by means of a portable infusion pump. Immediately before and after this, the LH and FSH responses to a test dose of 100 micrograms LH-RH were measured. Four days after discontinuation of the treatment, so that LH and FSH could be measured, blood was sampled every 10 minutes for a period of 6 hours, during which 20 micrograms LH-RH was injected intravenously every hour. Finally, a test dose of 100 micrograms LH-RH was given. The whole procedure was repeated at least 6 weeks later, but this time hourly injections of 100 micrograms LH-RH were given 4 days after discontinuation of the pulsatile LH-RH treatment. Four days after the pulsatile LH-RH treatment was stopped, increased LH and FSH responses to LH-RH were observed. These could be reduced by 6 injections, given hourly, of either 20 or 100 micrograms LH-RH. Although the totally released amount of both LH and FSH did not differ between the two treatment regimens irrespective of the LH-RH dose used, the response of both gonadotropins to the LH-RH test dose after the hourly 100 micrograms LH-RH injections was significantly lower. This indicated that desensitization can be attributed, at least in part, to a lower responsiveness of LH and FSH to LH-RH when pulsatile LH-RH is given. Low responses during treatment with pulsatile LH-RH could not be related to higher concentrations of plasma estradiol. We conclude that women with amenorrhea of suprapituitary origin who are treated with pulsatile LH-RH have a low state of responsiveness to LH-RH, which can be caused by the presence of the LH-RH and might be attributed in part to desensitization by LH-RH. Removal of the LH-RH results in an enhancement of the responsiveness, as the pituitary gland might have recovered from this desensitization.