Changes in the glycosylation pattern of circulating gonadotropins after acute administration of gonadotropin-releasing hormone in patients with anorexia nervosa
Abstract:To study the involvement of gonadotropin-releasing hormone (GnRH) in glycosylation of circulating gonadotropin isoforms in anorexia nervosa (AN), 14 amenorrhoic patients with AN, 14 age-matched volunteers in early follicular phase, and five normal-weight re-fed patients with AN were investigated under baseline conditions and after acute administration of GnRH. Plasma gonadotropins were assayed using IRMA before and after concanavalin A affinity chromatography. Baseline plasma gonadotropin levels were lower for… Show more
“…This method is the most effective and is approved at present to separate fractions of oligosaccharides united to asparagines according to its structure [17][18][19] , which facilitates the study of the glycoprotein hormones.…”
Objective: The purpose of this study was to evaluate the changes in the percentage of glycosylation of FSH and LH when using conjugated estrogens and tibolone as hormonal therapy (HT) in postmenopausal compared with regular menstrual cycles. Design: The study had three groups, with 10 participants in each group. The control group consisted of 10 women with normal menstrual cycles, a second group with 10 postmenopausal patients who received conjugated estrogens (Premarin 0.625 mg), and a third group had 10 patients who received tibolone (Livial 2.5 mg). All patients had hormonal determinations before and 6 months after the use of HT. Concavalin-A was used to separate the different glycosylated species of gonadotrophins, defined as unbound (UB: triantennary and bisecting oligosaccharides), weakly bound (WB: biantennary and truncated oligosaccharides), and firmly bound isoforms (FB: hybrid- and high-mannose-type oligosaccharides) in patients serum. Elusions containing the fractions with the isoforms were concentrated using Centriprep membranes (Amicon, Beverly, Mass., USA) and the different gonadotrophins isoforms were quantified by chemiluminescence using an automated system Immulite. Results: The pattern of distribution of gonadotrophins glycosylation in patients treated with conjugated estrogens and tibolone was similar to that observed in the control group with normal menstrual cycles, although with different glycosylation percentage. When the glycosylation percentages were compared for FSH, in the fraction UB the glycosylation did not have significant differences, but the fraction WB that has isoforms with high amounts of oligosaccharides showed a different percentage of glycosylation, where the recovery percentage was bigger with tibolone use (p < 0.05). The FB fraction had similar hormonal glycosylation with estrogens and tibolone use. When compared, LH glycosylation showed significant differences (p < 0.05) in the fraction UB with a bigger glycosylation degree, and in the fraction FB with a smaller glycosylation percentage, both in the tibolone group compared with conjugated estrogens use. Conclusions: Our results show that there are different percentages of glycosylation of gonadotrophins depending on type of HT (conjugated estrogens vs tibolone), and this could be of utility in young women with ovarian problem since to know the isoform that more favors to cellular activity could help a better therapeutic.
“…This method is the most effective and is approved at present to separate fractions of oligosaccharides united to asparagines according to its structure [17][18][19] , which facilitates the study of the glycoprotein hormones.…”
Objective: The purpose of this study was to evaluate the changes in the percentage of glycosylation of FSH and LH when using conjugated estrogens and tibolone as hormonal therapy (HT) in postmenopausal compared with regular menstrual cycles. Design: The study had three groups, with 10 participants in each group. The control group consisted of 10 women with normal menstrual cycles, a second group with 10 postmenopausal patients who received conjugated estrogens (Premarin 0.625 mg), and a third group had 10 patients who received tibolone (Livial 2.5 mg). All patients had hormonal determinations before and 6 months after the use of HT. Concavalin-A was used to separate the different glycosylated species of gonadotrophins, defined as unbound (UB: triantennary and bisecting oligosaccharides), weakly bound (WB: biantennary and truncated oligosaccharides), and firmly bound isoforms (FB: hybrid- and high-mannose-type oligosaccharides) in patients serum. Elusions containing the fractions with the isoforms were concentrated using Centriprep membranes (Amicon, Beverly, Mass., USA) and the different gonadotrophins isoforms were quantified by chemiluminescence using an automated system Immulite. Results: The pattern of distribution of gonadotrophins glycosylation in patients treated with conjugated estrogens and tibolone was similar to that observed in the control group with normal menstrual cycles, although with different glycosylation percentage. When the glycosylation percentages were compared for FSH, in the fraction UB the glycosylation did not have significant differences, but the fraction WB that has isoforms with high amounts of oligosaccharides showed a different percentage of glycosylation, where the recovery percentage was bigger with tibolone use (p < 0.05). The FB fraction had similar hormonal glycosylation with estrogens and tibolone use. When compared, LH glycosylation showed significant differences (p < 0.05) in the fraction UB with a bigger glycosylation degree, and in the fraction FB with a smaller glycosylation percentage, both in the tibolone group compared with conjugated estrogens use. Conclusions: Our results show that there are different percentages of glycosylation of gonadotrophins depending on type of HT (conjugated estrogens vs tibolone), and this could be of utility in young women with ovarian problem since to know the isoform that more favors to cellular activity could help a better therapeutic.
“…Releasing hormones such as gonadotropin-releasing hormone are known to induce not only changes in the quantity (greater numbers of molecules) but also in the quality (differences in glycosylation) of the secreted glycoprotein hormone by acting directly at translation and distal glycosylation levels (Ulloa-Aguirre et al 1995, Perez & Apfelbaum 1996, Lambert et al 1998, Savastano et al 1998, Timossi et al 1998. As far as the pituitary-thyroid axis is concerned, the availability of an efficient immuno-affinity method for the purification and concentration of serum TSH molecules (Schaaf et al 1995, Persani et al 1998) allows separation of different TSH isohormones.…”
Thyrotropin (TSH) is secreted not as one distinct hormone, but rather as a group of isohormones which differ in their oligosaccharide composition. Although the mechanisms regulating TSH glycosylation are not fully understood, there is strong evidence that TRH plays an important role. The aim of our study was to determine the dynamic influence of TRH on TSH microheterogeneity.Sera were obtained from euthyroid volunteers (n=20) before and 30, 60, 120, 180 and 240 min after intravenous, nasal and oral administration of TRH in three independent runs (randomized order, at a time-interval of 3 weeks between each run). TSH was immuno-concentrated and analysed by isoelectric focusing (IEF) and lentil lectin affinity chromatography. TSH immunoreactivity was measured by an automated second-generation TSH immunoassay. Overall, serum TSH concentrations reached maximal values 30 min after intravenous, 60 min after nasal and 180 min after oral TRH stimulation. IEF analysis revealed 63·3 3·3% of pituitary standard TSH (IRP 80/558) in the neutral pH range (8>pH>6). In contrast, 30 min after TRH stimulation 80·8 3·7% (P<0·001) and 60 min after TRH stimulation 44·9 2·2% (P<0·001) of the TSH of euthyroid probands were found in this pH range, whereas 180 min after TRH stimulation 58·4 2·3% (P<0·001) were detected in the acidic pH range (pH<6). This shift of TSH composition in euthyroidism after TRH stimulation was confirmed by lentil lectin analysis of TSH: core-fucose content of euthyroid TSH was 73·4 3·8% 30 min and 22·9 3·2% 120 min after TRH stimulation in contrast to basal (53·3 1·8%; P<0·001) and pituitary standard (IRP 80/558) TSH (63·0 0·9%; P<0·001).In conclusion, in euthyroidism, TRH stimulation timedependently changes the distribution pattern of the TSH isoforms from an alkaline and neutral to a more acidic one. This corresponds to the secretion of isohormones with altered bioactivity which could influence the fine-tuning of thyroid function.
“…Specifically, the gonadotropins have immature secretion patterns, with an increased follicle-stimulating hormone to luteinizing hormone (LH) ratio and decreased frequency and amplitude of luteinizing hormone bursts (4,7). Qualitative differences in the glycosylation patterns of gonadotropins are described in AN (8,9). These hormonal aberrations result in a prolonged follicular phase and an insufficient luteal phase (10).…”
Objective
To describe the hormonal adaptations and alterations in anorexia nervosa.
Methods
We performed a PubMed search of the English-language literature related to the pathophysiology of the endocrine disorders observed in anorexia nervosa, and we describe a case to illustrate these findings.
Results
Anorexia nervosa is a devastating disease with a variety of endocrine manifestations. The effects of starvation are extensive and negatively affect the pituitary gland, thyroid gland, adrenal glands, gonads, and bones. Appetite is modulated by the neuroendocrine system, and characteristic patterns of leptin and ghrelin concentrations have been observed in anorexia nervosa. A thorough understanding of refeeding syndrome is imperative to nutrition rehabilitation in these patients to avoid devastating consequences. Although most endocrinopathies associated with anorexia nervosa reverse with recovery, short stature, osteoporosis, and infertility may be long-lasting complications. We describe a 20-year-old woman who presented with end-stage anorexia nervosa whose clinical course reflects the numerous complications caused by this disease.
Conclusions
The effects of severe malnutrition and subsequent refeeding are extensive in anorexia nervosa. Nutrition rehabilitation is the most appropriate treatment for these patients; however, it must be done cautiously.
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