The Ratios of Serum Bioactive/Immunoreactive Luteinizing Hormone and Follicle-Stimulating Hormone in Various Clinical Conditions with Increased and Decreased Gonadotropin Secretion: Reevaluation by a Highly Sensitive Immunometric Assay*

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Abstract
Serum bioactive and immunoreactive LH and FSH were measured in clinical conditions with increased or decreased gonadotropin secretion. Gonadotropin immunoreactivity was measured using a conventional RIA (I) and an ultrasensitive immunofluorometric method (F). Bioactive (B) LH was assessed by the mouse interstitial cells in vitro bioassay, and B-FSH using the immature rat granulosa cell assay. Acute GnRH stimulation of adult men (n = 6) increased LH levels measured by the different methods 4.3- to 5.3-fold. The B/I ratio of LH increased from 2.34 .+-. 0.21 to 3.71 .+-. 0.36 (mean .+-. SEM) at 120 min (P < 0.05), but no change was found in the B/F ratio. After ovariectomy of premenopausal women ( = 6), the LH levels increased in 1 week 4- to 6-fold, the B/I ratio from 1.85 .+-. 0.22 to 2.59 .+-. 0.24, and the B/F ratio from 1.78 .+-. 0.22 to 2.90 .+-. 0.30 (P < 0.05 for both). In addition, the LH levels were measured during GnRH agonist treatment of ovarian carcinoma (n = 8), endometriosis (n = 8), and prostatic carcinoma after orchiectomy (n = 8). In the two former groups, serum B-LH decreased in 1 month to undetectable levels (<0.5 IU/L), and in the prostate cancer patients to 1.2 (0.8-1.9) IU/L (log mean and range of .+-.SEM). The concomitant decline of I-LH was to 1.5-1.9 IU/L in the agonist-treated female patients, and that of F-LH to 0.10-0.15 IU/L; in the prostate cancer patients, respectively, these values were 7-8 and 0.3-0.7 IU/L. The B/I and B/F ratios during the agonist treatments could only be calculated in the prostate cancer patients (in the others, B-LH became undetectable). The B/I ratio decreased from 2.34 .+-. 0.5 to 0.14 .+-. 0.03 (P < 0.01), but no suppression was found in the B/F ratio from a pretreatment value of 3.6 .+-. 0.8. B-, I-, and F-FSH levels were measured in the GnRH agonist-treated orchiectomized prostate cancer patients. The pretreatment level of B-FSH was 154 (137-175), that of I-FSH was 38.0 (34.4-42.0), and that of F-FSH was 39.8 (35.3-44.9) IU/L. The B/I ratio of FSH was 3.76 .+-. 0.49, and the B/F ratio was 3.53 .+-. 0.59. The mean B-FSH level decreased during treatment by 87-93.5%, that of I-FSH by 98%, and that of F-FSH by 91.5% (P < 0.01 for all). The pretreatment B/I (5.5 .+-. 1.9) and B/F (4.1 .+-. 1.1) ratios of FSH did not change significantly during treatment. In conclusion, major discrepancies were observed among the B-, I-, and F-LH levels measured. The levels correlated well at normal and high concentrations. In contrast, during GnRH agonist treatment, a pronounced parallel decrease was seen in B- and F-LH, whereas I-LH decreased clearly less. When detectable, the residual LH present during GnRH agonist treatment retained its full biological activity. The changes demonstrated earlier in the B/I ratios of serum LH in a variety of physiological and clinical conditions may have to be reevaluated using the new sensitive and specific immunometric techniques of LH measurement. Good agreement was observed among the FSH levels measured with the three assay methods, and no apparent change were found in the B/I ratio of FSH during GnRH agonist treatment.

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