Measurement of plasma free luteinizing hormone beta-subunit in women

Little is known about the physiological secretion of the free beta-subunit of LH (LH beta). The aim of this study was to compare in women the secretio n of LH beta, using sensitive and specific two-site immunoassays, with dime ric LH and the free common alpha-subunit (FAS). The LH beta assay does not recognize the dimeric LH and cross-reacts only with free hCG beta-subunit ( CG beta). Thus, all of the plasma samples were also tested with a highly sp ecific immunoradiometric assay for free CG beta. Molar concentrations (i.e, picomoles per L) were used to compare the plasma levels of LH and its free subunits. Plasma LH, LH beta, FAS, and CG beta levels were measured in fiv e normally cycling women during the early follicular phase and the ovulator y peak of LH. The pulsatile profiles of LH, LH beta, FAS, and CG beta were studied in five postmenopausal women before and 21 days after injection of a depot preparation of the GnRH agonist D-Trp(6) (3.75 mg, im) and in five women with functional hypothalamic amenorrhea (FHA), i.e. low plasma LH lev els, during pulsatile GnRH administration (20 mu g/pulse, 90 min, sc). Afte rward, one of the patients with FHA received a single sc injection of 1350 U recombinant human LH, and plasma LH, LH beta, FAS, and CG beta levels wer e measured and compared with the high plasma levels of one postmenopausal w oman. In cycling women, basal plasma LH beta and CG beta levels were below the de tection limit of the assays (1.34 and 0.65 pmol/L, respectively), and plasm a FAS levels were 13.60 +/- 0.13 pmol/L. During the LH surge, there was a p arallel increase in LH, LH beta, and FAS. Plasma CG beta levels remained un detectable. In normal postmenopausal women, basal plasma dimeric LH, LH bet a, and FAS levels were increased in parallel, and their pulsatile profiles were similar, without measurable plasma CG beta levels. After D-Trp(6) admi nistration, plasma LH and LH beta levels were completely suppressed, wherea s plasma FAS levels increased, and plasma CGB remained below 0.65 pmol/L. I n FHA women, basal plasma levels of LH and FAS were low, without detectable LH beta and CG beta levels. During pulsatile GnRH administration, LH beta became detectable, and pulses were synchronous with those of LH and FAS. Th e secretion of LH and LH beta was almost equimolar. Plasma CG beta levels r emained undetectable. In the patient with FHA, administration of recombinan t human LK increased only plasma LH levels, whereas plasma LH beta and FAS levels remained very low. In conclusion, when the production of dimeric LH increases, a concomitant, parallel, and almost equimolar hypersecretion of uncombined and biologicall y inactive LH beta occurs. Like the alpha-subunit, LH beta may be secreted in the dissociated free form. This can lead to pitfalls during clinical inv estigations if assays of free CG beta display some cross-reaction with free LH beta.