Effect of very high dose D-leucine6-gonadotropin-releasing hormone proethylamide on the hypothalamic-pituitary testicular axis in patients with prostatic cancer.

Warner, Barry A.; Worgul, T. J.; Drago, Joseph R.; Demers, Lawrence M.; Dufau, Maria L.; Max, Deverah T.; Santen, Richard J.

doi:10.1172/jci110940

Cited by 102 publications

(45 citation statements)

References 60 publications

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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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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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“…Unlike continuous infusions or bolus pharmacological doses of exogenous GnRH (21,22), consecutive intravenously pulsed submaximal doses of GnRH elicit preferential release of bioactive LH with a resultant significant increase in the plasma B:I LH ratio (2). The latter changes presumably reflect the accelerated 4 Values are means±SEM (n = 6 men in each group).…”

Section: Deconvolution Ofthe Gnrh-stimulated Bioactive Lhpulsesmentioning

confidence: 99%

“…However, few studies have examined the spontaneous pulsatile release of immunoactive LH in healthy older men (4)(5)(6), and no reports have delineated the characteristics of episodic bioactive LH secretion in such individuals. The assessment ofbioactive hormone is particularly important, since significant discrepancies can exist between immunoreactive and biologically active hormone concentrations.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, by combining bioassay and RIA, the ratio of bioactive to immunoactive LH (B:I ratio) can be used to estimate the quality of LH released under different circumstances (3). Such analyses in men with prostate cancer recently revealed significantly lower plasma B:I LH ratios in older men compared with those found in younger healthy men (4). In subsequent studies of a range of ages of men selected from a healthy population, single blood samples from older individuals were found to have significantly lower B:I LH ratios (5).…”

Section: Introductionmentioning

confidence: 99%

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Attenuated release of biologically active luteinizing hormone in healthy aging men.

et al. 1988

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To examine the biological quality and physiologically pulsatile mode of endogenous luteinizing hormone release in active, healthy aging men, we used the rat interstitial-cell testosterone in vitro bioassay to probe LH bioactivity in response to (a) endogenous gonadotropin-releasing hormone (GnRH) action (basal pulsatile bioactive LH secretion); (b) exogenous GnRH stimulation (10 gg IV pulses); and (c) inhibition of endogenous estrogen negative feedback (treatment with a nonsteroidal antiestrogen, tamoxifen). Basally, some healthy older men exhibited evidence of neuroendocrine dysfunction, reflected by irregular bursts of bioactive LH release followed by transiently low plasma bio:immuno (B:I) LH ratios. However, mean basal plasma bioactive LH concentrations, B:I ratios, and spontaneous LH pulse properties (peak frequency, amplitude, duration, and enhanced B:I ratios within LH peaks) were not altered in older men. On the other hand, augmentation of bioactive LH secretion and enhancement of plasma B:I ratios by pulsed injections of exogenous GnRH were either significantly reduced or absent in older men. In addition, although tamoxifen increased bioactive LH pulse frequency in both age groups and facilitated exogenous GnRH action in some subjects, older men increased their 12-h mean bioactive LH concentrations, B:I ratios, and bioactive LH peak amplitudes to a significantly lesser degree than young men.In summary, young and older healthy men exhibit similar mean basal plasma bioactive LH concentrations and spontaneous LH pulse properties. However, pituitary bioactive LH reserve is markedly attenuated in older men challenged with either exogenous GnRH or antiestrogen. Accordingly, we conclude that healthy aging men manifest an impaired secretory reserve for biologically active LH release.

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“…We then tried auto-transplanting endometrial tissue fragments under the kidney capsules of female rats and succeeded in establishing a simple endometriosis model. Potent GnRH agonists have been reported to downregulate the gonadal functions in chronic treatment of pharmacological doses and this paradoxical effect has been clinically utilized in treating a variety of hormonally responsive clinical disorders [7,8]. The paradoxical effects of GnRH agonists are thought to be mainly due to desensitization of the pituitary and gonads [9].…”

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confidence: 99%

Effects of TAP-144-SR, A Sustained-Release Formulation of a Potent GnRH Agonist, on Experimental Endometriosis in the Rat.

et al. 1991

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Effect of very high dose D-leucine6-gonadotropin-releasing hormone proethylamide on the hypothalamic-pituitary testicular axis in patients with prostatic cancer.

Cited by 102 publications

References 60 publications

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

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

Attenuated release of biologically active luteinizing hormone in healthy aging men.

Effects of TAP-144-SR, A Sustained-Release Formulation of a Potent GnRH Agonist, on Experimental Endometriosis in the Rat.

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