A luteinizing hormone-releasing hormone agonist decreases biological activity and modifies chromatographic behavior of luteinizing hormone in man.

Evans, Robert M.; Doelle, Gregory C.; Lindner, J; Bradley, Vanessa; Rabin, David

doi:10.1172/jci111200

Cited by 110 publications

(23 citation statements)

References 13 publications

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“…Our clinical results also attest to the high efficacy of microcapsules (11). In addition, the immunoreactive LH produced after chronic stimulation with LH-RH agonists was reported to have decreased biological activity (18,19).…”

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confidence: 73%

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Inhibition of growth of a prolactin and growth hormone-secreting pituitary tumor in rats by D-tryptophan-6 analog of luteinizing hormone-releasing hormone.

Torres‐Alemán¹,

Redding²

1985

Proc. Natl. Acad. Sci. U.S.A.

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The effect of long-term administration of analogs of luteinizing hormone-releasing hormone (LH-RH) and somatostatin on the growth of the growth hormone (GH)-and prolactin (PRL)-secreting rat pituitary GH3 tumor was investigated. Daily administration of tg/day) (Oss, Holland). Somatostatin analog cyclo(Pro-Phe-DTrp-Lys-Thr-Phe) (Veber cyclic hexapeptide) (12) was synthesized in our laboratory or supplied by J. Sandow and R. Geiger (Hoechst, Frankfurt M, FRG). Somatostatin analog D-Phe-Cys-Phe-t-Trp-Lys-Thr-Cys-Thr-NH2 related to the octapeptide of Bauer (13) was synthesized in our laboratory by solid-phase methods described previously (14).Female Wistar/Furth rats (80-100 g, Harlan SpragueDawley, Indianapolis, IN) were inoculated s.c. in the scapular region with OH3 pituitary tumor cells (obtained from the American Type Culture Collection). The animals were housed 5-7 per cage in a temperature-and light-controlled room. Five to seven animals were used per experimental group. In the first experiment, the treatment with peptides was started before tumors appeared, while in subsequent experiments, peptide administration was initiated when 50-100% of the animals showed well-developed tumors. Tumors were measured weekly with microcalipers and tumor volumes were calculated as described (7). Experiment I. Three days after inoculation of 1 X 106 GH3

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confidence: 73%

“…In any case, ovarian suppression after chronic [D-Trp6]LH-RH administration may occur in the presence of high immunoreactive serum LH levels (18,19). However, the antitumoral activity of [D-Trp6]LH-RH could be related in part to a direct action on this agonist on the pituitary tumor cells.…”

mentioning

confidence: 99%

Inhibition of growth of a prolactin and growth hormone-secreting pituitary tumor in rats by D-tryptophan-6 analog of luteinizing hormone-releasing hormone.

Torres‐Alemán¹,

Redding²

1985

Proc. Natl. Acad. Sci. U.S.A.

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“…In adults, such a condition (e.g. after long term treatment with GnRH agonist) is related to decreased B/I ratio of circulating LH (27)(28)(29). Inasmuch as the acute GnRH stimulation was able to increase the B/I ratio only in CD, this response may require priming of the pituitary by previous GnRH pulses.…”

Section: Discussionmentioning

confidence: 99%

LH Measurements by in Vitro Bioassay and a Highly Sensitive Immunofluorometric Assay Improve the Distinction between Boys with Constitutional Delay of Puberty and Hypogonadotropic Hypogonadism

Haavisto

Dunkel

Pettersson³

et al. 1990

Pediatr Res

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ABSTRACT. The basal and gonadotropin-releasing hormone (GnRH) stimulated levels of LH were measured in 21 boys with delayed puberty using conventional RIA, mouse interstitial cell in vitro bioassay (B-LH), and a highly sensitive immunofluorometric method (F-LH). On the basis of subsequent clinical follow-up, the subjects were diagnosed as idiopathic constitutional delay of puberty (CD, n = 13) or hypogonadotropic hypogonadism (HH, n = 8). The basal RIA LH levels were similar in the two diagnostic groups (HH, 2.92 f 0.76, CD 3.53 -C 1.37 IU/L). In contrast, the mean basal B-LH was significantly lower in boys with H H than with CD (1.10 2 0.45 versus 2.91 & 1.23 IU/L; p < 0.01). A similar finding was made by F-LH measurements which were clearly lower in the H H than the CD group (0.073 f 0.04 versus 1.71 -C 0.97 IU/L, p < 0.01). Also upon GnRH stimulation (3.5 pg/kg i.v.), the distinction between the CD and H H groups was better with the B-LH and F-LH measurements. The basal B/I ratio of the CD group (0.90 f 0.43) was more than that of the H H group (0.42 f 0 . 2 5 ,~ < 0.01) and this ratio increased significantly (more than 2-fold, p c 0.01) during GnRH stimulation in the CD group, but not in the HH patients. Such differences were not found between the B/F ratios of the CD and H H groups. Measurements of basal and GnRH stimulated B-and F-LH levels clearly improved the distinction between CD and HH in comparison to the conventional RIA method, due to the low sensitivity and likely cross-reactions with some non-LH constituents of serum in the latter assay. This problem is, to a great extent, eliminated by better sensitivity and specificity of B-LH and F-LH measurements. For the same reasons, the difference in B/I ratios between the CD and H H samples, and the increased B/I ratio after GnRH stimulation in the CD group, were not observed in B/F ratios. In conclusion, the measurements of basal and GnRH-stimulated concentrations of serum B-LH and F-LH clearly improve the differential diagnostics between CD and HH. The discrepancies measured between the B/I and B/F ratios in these samples call for reevaluation of the bio/immuno ratios of circulating LH. (Pediatr Res 27: 211-214, 1990) Abbreviations B/F ratio, ratio of serum B-LH/F-LH concentrations B/I ratio, ratio of serum B-LH/I-LH concentrationsB-LH, bioactive LH CD, constitutional delay of puberty F-LH, immunoreactive LH measured by immunofluorometric assay GnRH, gonadotropin-releasing hormone hCG, human chorionic gonadotropin HH, hypogonadotropic hypogonadism I-LH, immunoreactive LH measured by radioimmunoassay CV. coefficient of variation CD and HH pose a diagnostic problem in pediatric endocrinology. This differentiation is important for prognostic reasons and to avoid too long androgen treatment of children with CD. No hormonal measurement has thus far proven to be absolutely reliable in discriminating the two conditions (1, 2). Basal levels of immunoreactive LH and FSH show no clear differences (3-5), and even after stimulation tests with GnRH and hCG some ...

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“…These re sults as well as clinical evidence indicate that sustained treatment with GnRH ago nists most likely abolishes pituitary func tion, in spite of the fact that gonadotropin radioimmunoassays based on polyclonal an tibodies do not show this effect. This hy pothesis is sustained by the work of Evans et al [10], who showed that GnRH agonists markedly decrease bioactive LH but at the same time induce the appearance of slowmigrating immunoreactive LH on Sephadex columns.…”

Section: Introductionmentioning

confidence: 88%

Absence of Immunoreactive Luteinizing Hormone following Gonadotropin-Releasing Hormone Agonist Therapy in Women with Endometriosis

Bischof

Herrmann

1988

Gynecol Obstet Invest

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Pituitary desensitization following infusion of gonadotropin-releasing hormone (GnRH) is measurable if bioactivity instead of immunoreactivity is considered. We hypothesized that GnRH agonist therapy induces the same kind of desensitization, but that radioimmunoassays (RIA) for gonadotropins based on polyclonal antibodies cannot show this effect because they recognize inactive fragments of gondadotropins. To test this hypothesis we measured luteinizing hormone (LH) with two different assays: one RIA was based on a polyclonal rabbit anti-hLH, while the other one was an immunoradiometric assay (IRMA) based on 2 different mouse monoclonal anti-hLH. LH measurements were performed on plasma samples obtained from 13 women with laparoscopically proven endometriosis and treated with microcapsules of the GnRH agonist D-Trp6-GnRH (Ferring) once a month. The correlation between LH measurements with both assays in 36 control plasma samples and in another 13 samples obtained before treatment in women with endometriosis was excellent (r = 0.959). In contrast, in women treated with GnRH agonist, the RIA yielded values ranging from undetectable to 12 mIU/ml, whereas 60 out of 66 values were undetectable with the IRMA. We conclude that the monoclonal anti-hLH antibodies in the IRMA either recognize an epitope close to the active site and/or do not recognize the biologically inactive LH fragments which are known to be produced during GnRH agonist therapy. Thus, monoclonal-antibody-based IRMA provide a new and interesting clinical tool to follow the effects of therapies which desensitize the gonadotropic function of the pituitary.

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A luteinizing hormone-releasing hormone agonist decreases biological activity and modifies chromatographic behavior of luteinizing hormone in man.

Cited by 110 publications

References 13 publications

Inhibition of growth of a prolactin and growth hormone-secreting pituitary tumor in rats by D-tryptophan-6 analog of luteinizing hormone-releasing hormone.

Inhibition of growth of a prolactin and growth hormone-secreting pituitary tumor in rats by D-tryptophan-6 analog of luteinizing hormone-releasing hormone.

LH Measurements by in Vitro Bioassay and a Highly Sensitive Immunofluorometric Assay Improve the Distinction between Boys with Constitutional Delay of Puberty and Hypogonadotropic Hypogonadism

Absence of Immunoreactive Luteinizing Hormone following Gonadotropin-Releasing Hormone Agonist Therapy in Women with Endometriosis

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