Contrasts in the gonadotropin-releasing hormone dose–response relationships for luteinizing hormone, follicle-stimulating hormone and α-subunit release in young versus older men: appraisal with high-specificity immunoradiometric assay and deconvolution analysis

Abstract

The secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) is regulated by gonadotropin-releasing hormone (GnRH). As men age, mean serum concentrations of immunoreactive gonadotropic hormones tend to increase, while serum testosterone concentrations tend to decline. To evaluate age-related changes in gonadotroph cell function, we have assessed the dose-dependent secretory responses of immunoreactive LH, FSH and alpha-subunit to saline versus five doses of GnRH in older and young men. Ten older men, mean age 66 years (range 61-78), and nine young men, mean age 26 years (range 22-30), received iv bolus injections of GnRH (range 10-100 micrograms) in randomized order every 2 h, except that the 100-microgram dose was always given last. Blood samples for immunoradiometric assays of serum LH, FSH and alpha-subunit concentrations were obtained every 10 min for a total of 12 h, which included a 2-h preinjection baseline. Deconvolution analysis was performed to estimate gonadotropin and alpha-subunit secretory burst mass, amplitude and duration, as well as endogenous LH, FSH and alpha-subunit half-lives. The mean (+/- SEM) baseline 2-h serum FSH (IU/I) concentration was higher in older than younger men (5.9 +/- 0.8 vs 3.8 +/- 0.5, p < 0.05). The mean 2-h serum LH concentrations after GnRH were significantly higher than corresponding values in young men at GnRH doses of 25, 50 and 75 micrograms, and in the case of FSH at GnRH doses of 10 and 25 micrograms. Non-linear curve-fitting of these dose-response relationships revealed that the calculated maximal mean 2-h serum LH concentration response (IU/l) was higher in older than young men following GnRH stimulation: 15.4 (13.5-16.2) vs 10.8 (8.7-12.1) (95% confidence interval). The maximal mean 2-h serum FSH concentration response (IU/l) was also significantly higher in older men: 11.9 (10.2-13.1) versus 8.6 (7.2-9.6). Maximal alpha-subunit responses (microgram/l) were similarly increased in the older cohort: 1.16 (0.99-1.25) vs 0.83 (0.71-0.91). The incremental LH (p < 0.05) and FSH (p < 0.01) secretory burst mass from 10 to 25 micrograms GnRH was significantly greater in older than younger men. The LH and FSH half-lives and second component alpha-subunit half-lives were similar in older and young men. In addition, secretory burst durations were invariant of age. In contrast, by non-linear curve-fitting, the calculated mass of LH secreted was higher in older men at 13.5 (11.8-15) vs 10.6 (9.2-11.7) IU/l of distribution volume (p < 0.05) for the maximal absolute mass and 11.3 (9.5-12.7) vs 7.4 (6.0-8.4) IU/l (p < 0.05) for the maximal incremental mass of LH secreted after GnRH. The estimated maximal mass of FSH secreted after GnRH also was higher in older men: 4.6 (3.4-5.5) vs 3.2 (2.9-3.4) IU/l (p < 0.01). Finally, calculated maximal GnRH-stimulated alpha-subunit secretory burst mass was statistically greater in older individuals: 2.3 (1.8-2.5) vs 1.6 (1.4-1.8) micrograms/l. In contrast, half-maximally effective GnRH doses were not different in the two a...

Abnormal FSH Hypersecretion as an Endocrinological Manifestation of POEMS Syndrome.

“…Stimulation with LH-RH usually causes greater gonadotropin secretion [9]. In the present two patients, stimulation with LH-RH resulted in exaggerated (Case 1) and normal (Case 2) responses of LH, whereas the FSH response was blunted in both patients (Fig.…”

“…The basal gonadotropin levels in the elderly may vary depending upon the decreased testicular function due to aging [8][9][10], but the basal levels of testosterone and estradiol in both patients were within the normal range for their ages. Stimulation with LH-RH usually causes greater gonadotropin secretion [9].…”

Two-week pulsatile gonadotropin releasing hormone infusion unmasks dual (hypothalamic and Leydig cell) defects in the healthy aging male gonadotropic axis

“…Two recent studies evaluating bioactive or immunoreactive LH release after graded submaximal bolus doses of GnRH suggested increased age-related (maximal) LH secretion (19,20 …”

Analysis of bidirectional pattern synchrony of concentration-secretion pairs: implementation in the human testicular and adrenal axes

“…LH concentrations were assayed in duplicate by specific LH ␤-subunit-directed two-site monoclonal immunoradiometric assay (IRMA) (Nichols Laboratories, San Juan Capistrano, CA) (21,49). The sensitivity of the LH assay is 0.2 IU/l (First International Reference Preparation), and there is Ͻ0.03% cross-reactivity with free ␣-FSH or TSH (42,49,50,52). The intraand interassay coefficients of variation (CVs) are Ͻ8% and Ͻ10%, receptively.…”