Effects of follicle-stimulating hormone and human chorionic gonadotropin on gonadal steroidogenesis in two siblings with a follicle-stimulating hormone β subunit mutation

Objective To quantify gonadal steroid responses to different gonadotropin regimens. Design Transversal clinical study. Setting Academic medical center. Patient(s) A 41-year-old woman and her 37-year-old brother with isolated FSH deficiency due to a homozygous Tyr76X FSH β subunit gene ( FSHB ) mutation. Intervention(s) Initially, serial LH samples were drawn overnight. After 2-day dexamethasone suppression, steroids were measured at baseline and after hCG, recombinant FSH, or hCG + recombinant FSH administration. Main Outcome Measure(s) Pulse number, peak amplitude, and mean overnight LH levels, as well as basal and stimulated FSH, LH, T, E 2 , DHEAS, 17α-hydroxyprogesterone (17-OHP), and androstenedione (A). Result(s) The mean ±SD overnight LH was 49.2 ± 5.7 mIU/mL and 9.1 ± 2.9 mIU/mL; there were 8 pulses/8 hours and 9 pulses/9 hours, with mean amplitudes of 53.4 ± 6.5 mIU/mL and 11.7 ± 1.9 mIU/mL, for the woman and man, respectively. There was no steroid response to recombinant FSH, hCG, or hCG + recombinant FSH in the woman. In the man, T increased after hCG, recombinant FSH, and hCG + recombinant FSH, whereas E 2 , A, and 17-OHP increased only after hCG + recombinant FSH. Conclusion(s) This report constitutes the first detailed endocrine study of a man with isolated FSH deficiency due to an FSHB mutation and suggests that FSH may have a positive regulatory effect on healthy LH-stimulated Leydig cells, probably mediated by its primary action on Sertoli cells, in a paracrine mechanism.