LH and FSH responses to luteinizing releasing hormone in normal fertile women.
These studies were designed to permit calculation of bioassay dose-response curves for luteinizing releasing hormone (LRH) during three phases of the menstrual cycle in normal women. No previous data permit such estimations. Synthetic LRH was administered as a single i.v. bolus injection to 18 normal women. The dose levels were 30, 100, and 300 mug administered in the follicular, preovulary, or luteal phase of the menstrual cycle in a 3(2) factorial design. Each subject was injected with the same dose in two different phases of the same cycle. The total number of injections given to the entire group of women was 36. For comparative purposes, the same doses (30, 100, and 300 mug) were administered to eugonadal men. In absolute as well as in relative terms, the highest maximal responses were observed in the preovulatory phase, and the lowest in the follicular phase. Measured as the area under the time-response curve, the highest maximal responses were observed in the luteal phase. The duration of the elevation in LH and FSH in response to LRH showed no significant relation to the phases of the cycle but, for both hormones, was related to the dose of LRH administered. Dose-response curves were established for both LH and FSH in all three phases of the cycle, but only in the preovulatory and luteal phases were the F ratios significant for LH. For FSH, the F ratio was only significant in the luteal phase. The potency of LRH was found to increase throughout the cycle, culminating in the luteal phase. The potency in the early follicular phase was similar to that in normal, adult, human males. Throughout these studies the FSH:LH ratio remained less than one. During the normal menstrual cycle follicle growth is initiated by FSH secretion and the FSH:LH ratio is greater than one. These findings indicate that a factor other than the decapeptide, LRH, must stimulate FSH secretion during the follicular phase. Since any modulating hormonal factors (e.g., gonadal steroids) would be present during our studies, modulation of pituitary response to endogenous LRH can not explain the relative increase in FSH (compared to LH) seen in the early follicular phase of women. Lastly, the slopes of the dose-response curves for LRH stimulation of LH vary with phase of the menstrual cycle. The slope was least in follicular phase, greater with ovulatory phase, and greatest for luteal phase (when LH-FSH secretion is lowest). These data indicate that the differences in response to LRH are not simply alteration of potency (or quantitative differences) but differences in a qualitative response. Furthermore, endogenous LRH secretion must be lowest during the luteal phase, when response to exogenous LRH is greatest. It is common to test pituitary LH-FSH secretory ability by administering 100 mug of LRH intravenously. The 95% confidence intervals for the relative maximal responses to 100 mug LRH in normal, fertile women on the third day of the menstrual cycle were 200%-700% for LH, and 150-200% for FSH.
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood*; D008598:Menstruation; D013997:Time Factors
D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone