SCREENING OF THE MUTATIONS IN LUTEINIZING-HORMONE BETA-SUBUNIT IN PATIENTS WITH MENSTRUAL DISORDERS

Objective: To evaluate the clinical significance of the LH consisting of a mutant beta-subunit (Trp(8) to Arg(8) and Ile(15) to Thr(15)). De sign: Clinical and biochemical studies. Setting: Fertility center at t he University Hospital and its research laboratory. Patients: Fifty-on e patients with menstrual disorders and three homozygote cases and two heterozygote cases of the mutant LH who were reported previously. Int erventions: Nucleotide mutations of the LH beta gene in patients with menstrual disorders were screened using techniques of the polymerase c hain reaction and restriction fragment length polymorphism. Immunologi c and biologic activities of the mutant LH and endocrinologic profiles in the affected women were evaluated. Main Outcome Measures: Serum LH levels measured with different immunoassay kits; serum FSH and LK on the GnRH test; serum thyroid-stimulating hormone, PRL, T, and androste nedione; ultrasound examination of the ovaries; clinical hyperandrogen ic symptoms; and biologic activity of LH. Results: Two cases of homozy gotes and four of heterozygotes affected by the LH beta gene mutations were discovered in the current study through screening of patients wi th menstrual disorders. Serum LH levels in the homozygote cases were u ndetectable using a LH immunoassay kit, whereas levels in the heterozy gote cases showed reduced detectability with the kit. However, the rat io of the mutant LH values in the bioassay to those in the immunoassay was higher in the homozygote group than that in the control subjects. Response patterns of serum gonadotropins to GnRH in the homozygote we re similar to those in patients with polycystic ovary syndrome. Conclu sion: The mutations of LH beta-subunit might be related to menstrual d isorder in some patients.