A preponderance of basic luteinizing hormone (LH) isoforms accompanies inappropriate hypersecretion of both basal and pulsatile LH in adolescents with polycystic ovarian syndrome

We recently demonstrated that adolescent girls with polycystic ovarian synd rome (PCOS) exhibit augmented LH secretion due to an increase in immunofluo rometric and deconvolution-estimated LH secretory burst mass and pulse freq uency. Concurrently, we inferred either a prolongation of apparent (endogen ous) LH half-life or elevated basal (nonpulsatile) LH release in PCOS. The in vivo half-life of LH molecules can be affected by the oligosaccharide si de-chains, which also modify in vitro bioactivity and electrostatic change. Accordingly, as a surrogate estimator of altered endogenous LH half-life a nd/or biopotency in PCOS, we characterized the isoelectric properties of se creted LH isoforms and determined their in vitro biological activity in ado lescent girls with PCOS compared with healthy age-matched eumenorrheic cont rols. To this end, 12-h (overnight) serum samples from PCOS patients (n = 1 2) and normal adolescents (n = 10) were pooled by subject. Bioactive LH con centrations were then quantitated in a rat Leydig cell in vitro bioassay, a nd immunological activity was determined by immunofluorometry. The distribu tion of LH isoforms was evaluated by preparative chromatofocusing (pH windo w, 10.5 to <4.0) of samples further combined to yield three independent ser um pools for each of the patient and control groups. Fasting serum concentr ations of 17-hydroxyprogesterone (17-OHP), androstenedione, testosterone, e strone, estradiol, and sex hormone-binding globulin were determined as poss ible endocrine correlates of LH isotypes. Mean serum concentrations of immu noreactive and bioactive LH in adolescents with PCOS were 3 and 2 times hig her than values in controls: immunoreactive: PCOS, 7.8 +/- 0.9; controls: 2 .6 +/- 0.3 IU/L (P < 0.001); and bioactive: PCOS, 52 +/- 10; controls, 25 /- 4.1 IU/L (P = 0.002), respectively. Bioactive LH concentrations correlat ed positively with 17-OHP (P = 0.022), androstenedione (P = 0.012), and tes tosterone (P = 0.046) concentrations in PCOS. Chromatofocusing of LH isofor ms disclosed greater LH immunoreactivity at pi Values greater than 8 and 7. 99-7.0 in adolescents with PCOS compared with controls (P = 0.031). The per centage of basic LH isoforms was related positively to serum concentrations of 17-OHP (P = 0.032), androstenedione (P = 0.046), and testosterone (P = 0.040). In conclusion, the present isotype analysis demonstrates elevated i n vitro LH bioactivity and a preponderance of basic LH isoforms in girls wi th PCOS. Since previously reported heterologous in vivo assays of LH kineti cs point. toward accelerated removal of such alkaline isotypes, our finding s would favor the earlier alternative hypothesis of inappropriate hypersecr etion of basal (interpulse) LH rather than prolongation of the LIH half-lif e as the mechanism for elevated interpulse serum LH concentrations in adole scents with PCOS. In ensemble, the foregoing data thus suggest S-fold ampli fication of basal LH secretion as well as both a heightened amplitude and f requency of the pulsatile mode of LH release in PCOS.