title: A preponderance of basic luteinizing hormone (LH) isoforms accompanies inappropriate hypersecretion of both basal and pulsatile LH in adolescents with polycystic ovarian syndrome.
abstract: We recently demonstrated that adolescent girls with polycystic ovarian syndrome (PCOS) exhibit augmented LH secretion due to an increase in immunofluorometric and deconvolution-estimated LH secretory burst mass and pulse frequency. Concurrently, we inferred either a prolongation of apparent (endogenous) 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 side-chains, which also modify in vitro bioactivity and electrostatic change. Accordingly, as a surrogate estimator of altered endogenous LH half-life and/or biopotency in PCOS, we characterized the isoelectric properties of secreted LH isoforms and determined their in vitro biological activity in adolescent girls with PCOS compared with healthy age-matched eumenorrheic controls. To this end, 12-h (overnight) serum samples from PCOS patients (n = 12) and normal adolescents (n = 10) were pooled by subject. Bioactive LH concentrations were then quantitated in a rat Leydig cell in vitro bioassay, and immunological activity was determined by immunofluorometry. The distribution of LH isoforms was evaluated by preparative chromatofocusing (pH window, 10.5 to <4.0) of samples further combined to yield three independent serum pools for each of the patient and control groups. Fasting serum concentrations of 17-hydroxyprogesterone (17-OHP), androstenedione, testosterone, estrone, estradiol, and sex hormone-binding globulin were determined as possible endocrine correlates of LH isotypes. Mean serum concentrations of immunoreactive and bioactive LH in adolescents with PCOS were 3 and 2 times higher 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 correlated positively with 17-OHP (P = 0.022), androstenedione (P = 0.012), and testosterone (P = 0.046) concentrations in PCOS. Chromatofocusing of LH isoforms 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 percentage 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 in vitro LH bioactivity and a preponderance of basic LH isoforms in girls with PCOS. Since previously reported heterologous in vivo assays of LH kinetics point toward accelerated removal of such alkaline isotypes, our findings would favor the earlier alternative hypothesis of inappropriate hypersecretion of basal (interpulse) LH rather than prolongation of the LH half-life as the mechanism for elevated interpulse serum LH concentrations in adolescents with PCOS. In ensemble, the foregoing data thus suggest 3-fold amplification of basal LH secretion as well as both a heightened amplitude and frequency of the pulsatile mode of LH release in PCOS.
authors.affiliation: Centro de Investigaciones Endocrinologicas, Hospital de Niños R. Gutierrez, Buenos Aires, Argentina.
authors.forename: M G
authors.initials: MG
authors.lastname: Ropelato
authors.forename: M C
authors.initials: MC
authors.lastname: Garcia-Rudaz
authors.forename: C
authors.initials: C
authors.lastname: Castro-Fernandez
authors.forename: A
authors.initials: A
authors.lastname: Ulloa-Aguirre
authors.forename: M E
authors.initials: ME
authors.lastname: Escobar
authors.forename: M
authors.initials: M
authors.lastname: Barontini
authors.forename: J D
authors.initials: JD
authors.lastname: Veldhuis
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000293:Adolescent; D000328:Adult; D000735:Androstenedione / Q000097:blood; D000818:Animals; D001681:Biological Assay; D002845:Chromatography; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D007985:Leydig Cells / Q000187:drug effects; D007986:Luteinizing Hormone / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D010507:Periodicity; D011085:Polycystic Ovary Syndrome / Q000503:physiopathology*; D051381:Rats; D013739:Testosterone / Q000097:blood
chemical_list: D013739:Testosterone; D000735:Androstenedione; D019326:17-alpha-Hydroxyprogesterone; D007986:Luteinizing Hormone