Effects of gonadotropin-releasing hormone on bioactivity of follicle-stimulating hormone (FSH) and microstructure of FSH, luteinizing hormone and sex hormone-binding globulin in a testosterone-based contraceptive trial: evaluation of responders and non-responders.

Only a proportion of normal men participating in testosterone-based contraceptive trials develop azoospermia (responders). This study analyzed whether serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) are qualitatively different between responders and non-responders. Determination of in vitro bioactive FSH after stimulation with gonadotropin-releasing hormone (GnRH) and analysis of molecular heterogeneity of serum FSH, LH and SHBG was carried out by chromatofocusing and concanavalin-A affinity chromatography in eight men who had participated in a previous contraceptive study with testosterone buciclate. Blood was withdrawn at 15-min intervals on two basal occasions and 30, 45 and 60 min after i.v. administration of GnRH (100 micrograms). Pools of sera were separated by chromatofocusing in the pH range 3-6 and by lectin chromatography on concanavalin A. Immunoreactive FSH, LH and SHBG were assayed in the eluates. Bioactive FSH was analyzed by the rat Sertoli cell bioassay. Serum bioactive FSH increased after GnRH stimulation, without significant differences between responders and non-responders. The chromatofocusing profiles of serum FSH showed a significant shift towards the less acidic region after GnRH. The isoform distribution was similar in responders and non-responders. No significant differences were found in the relative proportion of FSH, LH and SHBG retained by concanavalin A. It is concluded that the extent of suppression of sperm production by androgen administration cannot be foreseen either on the basis of the response of bioactive FSH to GnRH administration or from the glycosylation pattern of serum FSH, LH and SHBG.

[1]  E. Nieschlag,et al.  Potential of testosterone buciclate for male contraception: endocrine differences between responders and nonresponders. , 1995, The Journal of clinical endocrinology and metabolism.

[2]  M. Muyan,et al.  Secretion of lutropin and follitropin from transfected GH3 cells: evidence for separate secretory pathways. , 1994, Molecular endocrinology.

[3]  D. Phillips,et al.  Serum gonadotropin isoforms become more basic after an exogenous challenge of gonadotropin-releasing hormone in children undergoing pubertal development. , 1994, The Journal of clinical endocrinology and metabolism.

[4]  T. Naessén,et al.  17β‐Oestradiol counteracts the formation of the more acidic isoforms of follicle‐stimulating hormone and luteinizing hormone after menopause , 1994, Clinical endocrinology.

[5]  P. Schofield,et al.  Specific roles for the asparagine-linked carbohydrate residues of recombinant human follicle stimulating hormone in receptor binding and signal transduction. , 1994, Molecular endocrinology.

[6]  I. Harsch,et al.  Molecular heterogeneity of serum follicle‐stimulating hormone in hypogonadal patients before and during androgen replacement therapy and in normal men , 1993, Clinical endocrinology.

[7]  R. Wood,et al.  Pulsatile administration of gonadotropin-releasing hormone does not alter the follicle-stimulating hormone (FSH) isoform distribution pattern of pituitary or circulating FSH in nutritionally growth-restricted ovariectomized lambs. , 1993, Endocrinology.

[8]  K. Pettersson,et al.  Concanavalin A affinity chromatography of human serum gonadotropins: evidence for changes of carbohydrate structure in different clinical conditions. , 1993, The Journal of clinical endocrinology and metabolism.

[9]  E. Nieschlag,et al.  Biological and immunological properties of the international standard for FSH 83/575: isoelectrofocusing profile and comparison with other FSH preparations. , 1993, Acta endocrinologica.

[10]  I. Huhtaniemi,et al.  The bio/immuno ratio of plasma luteinizing hormone does not change during the endogenous secretion pulse: reanalysis of the concept using improved immunometric techniques. , 1992, The Journal of clinical endocrinology and metabolism.

[11]  E. Nieschlag,et al.  Microheterogeneity of pituitary follicle-stimulating hormone in male rats: differential effects of the chronic androgen deprivation induced by castration or androgen blockade. , 1992, Journal of molecular endocrinology.

[12]  G. Hammond,et al.  Molecular analyses of a human sex hormone-binding globulin variant: evidence for an additional carbohydrate chain. , 1992, The Journal of clinical endocrinology and metabolism.

[13]  W. Heyns,et al.  Genetic variation of human sex hormone-binding globulin: evidence for a worldwide bi-allelic gene. , 1992, The Journal of clinical endocrinology and metabolism.

[14]  K. Dahl,et al.  FSH isoforms, radioimmunoassays, bioassays, and their significance. , 1992, Journal of andrology.

[15]  G. Hammond,et al.  Expression and differential glycosylation of human sex hormone-binding globulin by mammalian cell lines. , 1991, Molecular endocrinology.

[16]  E. Nieschlag,et al.  Varying dose-response characteristics of different immunoassays and an in-vitro bioassay for FSH are responsible for changing ratios of biologically active to immunologically active FSH. , 1990, The Journal of endocrinology.

[17]  P. Kellokumpu-Lehtinen,et al.  The ratios of serum bioactive/immunoreactive luteinizing hormone and follicle-stimulating hormone in various clinical conditions with increased and decreased gonadotropin secretion: reevaluation by a highly sensitive immunometric assay. , 1990, The Journal of clinical endocrinology and metabolism.

[18]  E. Nieschlag,et al.  Diagnostic value of bioactive FSH in male infertility. , 1989, Acta endocrinologica.

[19]  V. Padmanabhan,et al.  Bioactive follicle-stimulating hormone responses to intravenous gonadotropin-releasing hormone in boys with idiopathic hypogonadotropic hypogonadism. , 1988, The Journal of clinical endocrinology and metabolism.

[20]  A. Ulloa-Aguirre,et al.  Immunological and biological potencies of the different molecular species of gonadotrophins. , 1988, Human reproduction.

[21]  L. Wide The regulation of metabolic clearance rate of human FSH in mice by variation of the molecular structure of the hormone. , 1986, Acta endocrinologica.

[22]  M. Sairam,et al.  Studies on pituitary follitropin X. Biochemical, receptor binding and immunological properties of deglycosylated ovine hormone , 1982, Molecular and Cellular Endocrinology.

[23]  K. Albertsson-Wikland,et al.  Change in electrophoretic mobility of human follicle-stimulating hormone in serum after administration of gonadotropin-releasing hormone. , 1990, The Journal of clinical endocrinology and metabolism.