Endocrine Abstracts

Background: The FSHB –211 G > T single nucleotide polymorphism (SNP) is known to affect pituitary FSH output by reducing the transcriptional activity of FSHB. Identifying the response of the pituitary to exogenous GnRH stimulation in subjects with FSHB -211 G > T SNP could provide useful information concerning the mechanisms regulating FSH synthesis and release.

Objectives: This study aimed to assess the pituitary response to a standardized GnRH stimulation test in patients with secondary hypogonadism (SH) according to the different FSHB -211 G/T genotypes (GG/GT/TT).

Materials and methods: 67 male patients receiving a GnRH stimulation test (0.1 mg intravenously, sampling at 2 time-points after administration) during clinical workup for SH between January 1997 and October 2018 were retrospectively selected in our university-based referral centre. Linear longitudinal mixed-effect models were used to assess the effects of SNP genotype on FSH and LH levels over time via additive and recessive models.

Results: A marked increase in serum FSH and LH following administration of GnRH with a statistically significant linear trend was found (P < 0.0001 for both models). In both the additive and recessive models, the main effect of T allele(s) did not reach statistical significance concerning changes of FSH levels (P = 0.9473 and P = 0.9467, respectively), albeit interaction effects over time were significant (P = 0.0219 and P = 0.0276). Main and interaction effects on LH-surge were significant in both the additive (P = 0.029 and P = 0.0013) and recessive model (P = 0.0033 and P = 0.0016). The peak of serum LH levels was significantly higher in TT carriers than in GT and GG carriers (P = 0.012)

Discussion and conclusions: The promoter polymorphism FSHB -211 G > T affects the pituitary response to exogenous GnRH stimulation by reducing FSH and, surprisingly, increasing LH outputs in patients with secondary hypogonadism.

Supported by the German Research Foundation CRU326 ‘Male Germ Cells’.