Basal and gonadotropin-releasing hormone-releasable serum follicle-stimulating hormone charge isoform distribution and in vitro biological-to-immunological ratio in male puberty.
Follicle-stimulating hormone is synthesized and secreted as a mixture of heterogeneous isoforms that differ from each other in carbohydrate structure, biological potency, and plasma half-life. The relative abundance of the FSH isoforms will depend on the endocrine status of the donor at the time of sample collection. In the present study, we attempted to define the impact of the changing endocrine milieu characteristic of male puberty on the charge heterogeneity and plasma half-life of the serum FSH isoforms released under endogenous and exogenous GnRH drives, and examined whether such a varying hormone milieu modifies the capability of the circulating hormone to trigger intracellular signal transduction at the human FSH receptor level. Forty healthy male subjects at Tanner stages (Ts) 1 to 5 were sampled at 10 min intervals for 10 h. Serum from successive samples collected across 2-4 h intervals containing FSH released under basal, low-dose (10 microg), and high-dose (90 microg) exogenous GnRH-stimulated conditions was subjected to preparative chromatofocusing and tested for bioactivity employing a homologous cell in vitro bioassay system. Deconvolution analysis was applied to estimate the apparent endogenous FSH plasma half-life in samples obtained after administration of low-dose exogenous GnRH. Under all conditions studied, serum FSH charge isoforms were distributed along a pH range of 7.0 to less than 3.0. Comparisons across the different Tanner stages revealed a significant and selective increase in the ratio of FSH isoforms with elution pH values <4.50 relative to those with values >/=4.50 at Ts-2. At Ts-3, this ratio returned to that present at Ts-1, to decline thereafter during the ensuing pubertal stages. Serum bioactive FSH concentrations progressively increased (from 3.72 +/- 1.3 to 16.2 +/- 5.3 IU/L) throughout puberty, and in all conditions bioactive FSH concentrations exceeded those detected by a specific radioimmunoassay. The biological to immunological (B:I) FSH ratio at baseline was significantly (p < 0.05) lower at Ts-1 and Ts-2 (1.33 +/- 0.30 and 1.62 +/- 0.34, respectively) than at more advanced stages of pubertal development (2.28 +/- 0.20, 2.96 +/- 0.38, and 2.77 +/- 0.63 at Ts-3-, 4-, and -5, respectively) Similar differences were detected in samples containing FSH molecules released after low- and high-dose GnRH administration. The apparent endogenous FSH half-life of the deconvolved GnRH-induced FSH pulses was similar in the five study groups. These results demonstrate that the transition from infancy to sexual maturity in men is accompanied by qualitative changes in the circulating FSH isoform mixture. Although the changes in FSH glycosylation occurring throughout puberty are not of sufficient magnitude to alter the survival of the gonadotropin in circulation, they allow preferential secretion of bioactive FSH. The enrichment of the circulating mix of FSH isoforms with highly bioactive variants throughout spontaneous puberty may potentially favor the development of spermatogenesis and acquisition of reproductive competence.
Olivares
A
A
Research Unit in Developmental Biology, Hospital de Pediatria, Centro Médico Nacional S. XXI, IMSS, México 06700 D.F., Mexico.
Söderlund
D
D
Castro-Fernández
C
C
Zariñán
T
T
Zambrano
Elena
E
Méndez
J P
JP
Ulloa-Aguirre
A
A
D000293:Adolescent; D000328:Adult; D001681:Biological Assay; D002460:Cell Line; D002648:Child; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood* / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage*; D006062:Gonadotropins / Q000097:blood; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D020033:Protein Isoforms / Q000097:blood; D011627:Puberty / Q000097:blood*; D013739:Testosterone / Q000097:blood
D006062:Gonadotropins; D020033:Protein Isoforms; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D005640:Follicle Stimulating Hormone