Defective regulation of glycoprotein free alpha-subunit in males with isolated gonadotropin-releasing hormone deficiency--a clinical research center study

Details

Serval ID
serval:BIB_FF6197CC04BA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Defective regulation of glycoprotein free alpha-subunit in males with isolated gonadotropin-releasing hormone deficiency--a clinical research center study
Journal
Journal of Clinical Endocrinology and Metabolism
Author(s)
Pralong  F. P., Pavlou  S. N., Waldstreicher  J., Crowley, W. F., Jr. , Boepple  P. A.
ISSN
0021-972X (Print)
Publication state
Published
Issued date
12/1995
Volume
80
Number
12
Pages
3682-8
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Dec
Abstract
During long term replacement with a GnRH regimen that restores their gonadotropin and sex steroid levels to normal, men with idiopathic hypogonadotropic hypogonadism (IHH) exhibit excessive secretion of pituitary free alpha-subunit (FAS). To characterize further the dose and duration of exogenous GnRH required to elicit this response, FAS, LH, FSH, and testosterone were determined during the first 8 weeks of GnRH administration in 10 men with IHH. The GnRH dose was increased stepwise every 2 weeks from 5 to 100 ng/kg every 2 h. Hormonal responses were compared with normative data for both pubertal boys and adult men. Low baseline levels of LH (mean +/- SEM, 0.9 +/- 0.03 IU/L), FSH (2.5 +/- 0.4 IU/L), FAS (148 +/- 21 ng/L), and testosterone (2.5 +/- 0.3 nmol/L) increased progressively after GnRH replacement. Mean FAS levels and pulse amplitudes significantly exceeded those in normal adult men by 4-6 weeks when their LH responses to GnRH administration remained below adult norms. By week 8 (50 ng GnRH/kg every 2 h), mean levels of LH, FSH, and FAS (13.7 +/- 2.1 IU/L, 15.4 +/- 4.0 IU/L, 627 +/- 75 ng/L, respectively) significantly exceeded adult male concentrations (P < 0.03). However, mean LH and FSH concentrations were not significantly different from midpubertal controls, in whom FAS levels were comparable to those in normal adults, verifying the excessive nature of FAS secretion relative to intact gonadotropins in the IHH patients. As this imbalance between FAS and dimeric gonadotropin secretion was established early in the current study when low doses of GnRH presumably resulted in low levels of receptor occupancy in vivo, it does not appear to result from partial pituitary desensitization induced by pharmacological GnRH stimulation. Rather, it appears to represent an inherent property of the GnRH-deficient state that is unmasked when GnRH input to the pituitary is restored. Further work will be necessary to elucidate the mechanism of this apparent defect in FAS regulation in GnRH-deficient men.
Keywords
Adolescent Adult Dose-Response Relationship, Drug Follicle Stimulating Hormone/blood Glycoproteins/*blood Gonadotropin-Releasing Hormone/*deficiency/therapeutic use Humans Hypogonadism/blood/drug therapy Luteinizing Hormone/blood Male Reference Values Testosterone/blood
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Web of science
Create date
25/01/2008 16:26
Last modification date
20/08/2019 16:29
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