title: Testicular anti-mullerian hormone secretion is stimulated by recombinant human FSH in patients with congenital hypogonadotropic hypogonadism.
abstract: Serum anti-Mullerian hormone (AMH), a prepubertal Sertoli cell marker, declines during puberty as an early sign of testicular testosterone (T) production. When T synthesis or action is impaired, serum AMH is abnormally high in the first months after birth and at puberty but normal between these two periods. We postulated that FSH might be responsible for AMH up-regulation in the absence of androgen inhibition. To test this hypothesis, we administered recombinant human (rh) FSH to eight patients aged from 18-31 yr with untreated congenital hypogonadotropic hypogonadism. This situation is ideal to study the effect of FSH on AMH production because it avoids interference by endogenous gonadotropins and T. The patients received daily sc injections of 150 IU rhFSH for 1 month, followed in seven of them by a combined treatment of rhFSH plus human chorionic gonadotropin (hCG; 1500 UI im, twice a week) for 2 months. Gonadotropins, T, AMH, and inhibin B were measured in plasma before treatment every 10 d during rhFSH treatment and every month during combined rhFSH and hCG treatments. All hormones were at prepubertal levels before treatment. Although LH and T did not vary, AMH and inhibin B levels gradually increased after 20 d of FSH administration. However, in contrast to rhFSH alone, the combined rhFSH plus hCG stimulation of the testis dramatically suppresses the secretion of AMH and induced a modest but significant reduction of circulating inhibin B levels. We conclude that FSH stimulates AMH production in the testis when it is at a prepubertal stage. In addition, the decrease of serum AMH during combined rhFSH and hCG testicular stimulation is in agreement with the concept that during pubertal development and in adult life, the suppressive effect of LH-driven testicular androgens outweighs the stimulating effect of FSH on AMH production by Sertoli cells. Finally, the hCG-induced decrease in inhibin B suggests that in humans, as previously demonstrated in monkeys, testicular T is also able to inhibit inhibin B secretion.
authors.affiliation: Service d'Endocrinologie et des Maladies de la Reproduction, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, 94270 Le Kremlin Bicêtre cedex, France. jacques.young@bct.ap-hop-paris.fr
authors.forename: Jacques
authors.initials: J
authors.lastname: Young
authors.forename: Philippe
authors.initials: P
authors.lastname: Chanson
authors.forename: Sylvie
authors.initials: S
authors.lastname: Salenave
authors.forename: Michèle
authors.initials: M
authors.lastname: Noël
authors.forename: Sylvie
authors.initials: S
authors.lastname: Brailly
authors.forename: Martín
authors.initials: M
authors.lastname: O'Flaherty
authors.forename: Gilbert
authors.initials: G
authors.lastname: Schaison
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Rey
mesh_terms: D000293:Adolescent; D000328:Adult; D054304:Anti-Mullerian Hormone; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000494:pharmacology; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007006:Hypogonadism / Q000097:blood*; D007265:Inhibins / Q000097:blood; D017436:Kallmann Syndrome / Q000097:blood*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009095:Mullerian Ducts / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013735:Testicular Hormones / Q000097:blood / Q000378:metabolism*; D013737:Testis / Q000033:anatomy & histology
chemical_list: D006023:Glycoproteins; D011994:Recombinant Proteins; D013735:Testicular Hormones; C422364:inhibin B; D007265:Inhibins; D054304:Anti-Mullerian Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone