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Does the gonadotrophic axis play a role in the pathogenesis of Sertoli-cell-only syndrome?
E Leifke1, M Simoni, A Kamischke
1Institute of Reproductive Medicine of the University, Münster, Germany.
Abstract:
Infertile men with Sertoli-cell-only syndrome (SCO) have highly elevated serum FSH immunoactivity related to the degree of histological damage. The activity that serum FSH exerts at the target site depends on its glycosylation pattern and FSH receptor (FSHR) function. Either could be impaired, leading to failure of spermatogenesis. The aim of the present investigation was to study bioactivity and the glycosylation pattern of serum FSH and the occurrence of mutations in the FSH receptor in infertile patients with SCO compared to normal men. Blood was taken from 19 patients with bilateral testicular focal or complete SCO and eight normozoospermic controls. FSH bioactivity in serum was measured using an in-vitro FSH bioassay based on recombinant rat FSHR. The glycosylation pattern of serum FSH was determined by concanavalin A chromatography. Inhibin B was determined in serum using a recently available assay. Genomic DNA extracted from blood lymphocytes was amplified by PCR using primers specific for the FSHR and screened by single-stranded conformation polymorphism gel electrophoresis. Men with SCO showed significantly higher FSH in-vitro bioactivity (34.9 +/- 5.0 IU/l) than controls (9.6 +/- 0.8 IU/l: p < 0.01), as well as significantly elevated FSH immunoactivity (14.9 +/- 1.7 IU/l) compared to controls (3.1 +/- 0.5; p < 0.01). Immunoactivity of serum FSH was correlated with in-vitro bioactivity (r = 0.9; p < 0.001) and was related to the degree of testicular damage (proportion of SCO-tubules) (ANOVA: p < 0.001) and total testicular volume (r = -0.76; p < 0.01). An inverse relationship between serum FSH and inhibin B levels (r = -0.93; p < 0.001) was found. In the serum of SCO patients a slight increase in less glycosylated FSH isoforms was found (6.7 +/- 0.6% versus 3.6 +/- 0.3%; p < 0.05). No mutations of the FSHR were observed in SCO patients. We conclude that the spermatogenic failure observed in infertile patients with SCO histology and elevated FSH serum levels can be explained neither by a change in FSH bioactivity nor by mutations in the FSHR. The slight change in the FSH glycosylation pattern is probably related to higher hormonal secretion rates in SCO patients. The inverse relationship between serum FSH and inhibin B points to an intact endocrine testicular-pituitary circuit responsible for the compensatory increase of FSH in SCO.
Insights
Sertoli-cell-only syndrome (SCO) in infertile men is linked to high follicle-stimulating hormone (FSH) levels, but not due to altered FSH bioactivity or FSH receptor (FSHR) mutations. This suggests intact pituitary-testicular regulation despite impaired spermatogenesis.
Area of Science:
- Reproductive Endocrinology
- Male Infertility
- Spermatogenesis
Background:
- Sertoli-cell-only syndrome (SCO) is a cause of male infertility characterized by elevated serum follicle-stimulating hormone (FSH) immunoactivity.
- The biological activity of FSH, influenced by glycosylation and FSH receptor (FSHR) function, is crucial for spermatogenesis.
- Understanding the role of FSH bioactivity, glycosylation, and FSHR integrity is essential in infertile men with SCO.
Purpose of the Study:
- To investigate the bioactivity and glycosylation pattern of serum FSH in infertile men with SCO compared to normozoospermic controls.
- To screen for mutations in the FSH receptor (FSHR) gene in patients with SCO.
- To correlate FSH levels with testicular histology and inhibin B in SCO patients.
Main Methods:
- Serum FSH bioactivity was measured using an in-vitro bioassay.
- FSH glycosylation patterns were analyzed via concanavalin A chromatography.
- FSHR gene mutations were screened using PCR and single-stranded conformation polymorphism (SSCP) analysis.
Main Results:
- SCO patients exhibited significantly higher serum FSH bioactivity and immunoactivity compared to controls.
- Serum FSH immunoactivity strongly correlated with bioactivity, testicular damage, and inversely with inhibin B levels.
- A slight increase in less glycosylated FSH isoforms was observed in SCO patients; no FSHR mutations were detected.
Conclusions:
- Elevated FSH levels in SCO patients are not explained by altered FSH bioactivity or FSHR mutations.
- The observed changes in FSH glycosylation may reflect increased hormonal secretion rates.
- The inverse relationship between FSH and inhibin B suggests an intact pituitary-testicular feedback loop contributing to compensatory FSH elevation in SCO.