Pulsatile Gonadotropin-Releasing Hormone in Gonadotropin Deficient and Normal Men: Suppression of Follicle-Stimulating Hormone Responses by Testosterone*

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Abstract
To determine the role of testosterone (T) in modulating gonadotropin secretion during sexual maturation, we studied males with isolated gonadotropin deficiency (IGD) before and during T therapy and compared the results to those in normal men. Low dose (0.025 jug/kg) pulses of gonadotropinreleasing hormone (GnRH) were given every 2 h for 5 days to four males with IGD pretreated with T (IGD-T), and responses were compared to untreated IGD men. The same protocol was performed in four normal men. All IGD males had low gonadotropins on day 0. The mean preinjection LH and FSH rose to 4.4 ± 0.4 and 15.5 ± 2.5 mlU/ml, respectively, on day 5 in the IGD patients, while plasma T levels remained low (0.7 ± 0.2 ng/ml). T therapy, which produced adult plasma T levels, suppressed the rise in gonadotropins, particularly the FSH response. Preinjection LH and FSH levels on day 5 in the IGD-T patients were 2.5 ± 0.4 and 2.9 ± 1.0 mlU/ml, respectively. In normal men the GnRH-induced LH increments were of similar magnitude to the spontaneous LH peaks present on the control day 0. Projected LH and FSH, however, rose by 65% and 45%, respectively, during days 1 and 2 of GnRH pulses, before declining on day 3 when plasma T (7.2 ± 1.4 ng/ml) and estradiol (64 ± 7 pg/ml) were significantly elevated above the control day. Standard GnRH tests (2.5 jitg/kg), performed before and after the GnRH pulses, showed augmentation of the LH and FSH responses in IGD and to a lesser degree in IGD-T patients. In contrast, normal men showed a marked reduction in gonadotropin responses. The results in GnRH-deficient patients indicate that T treatment inhibits FSH, and to a lesser extent LH secretion, by a direct action on the pituitary gland. A similar mechanism, where increasing gonadal steroid concentrations limit pituitary responses, may explain the small FSH increase to GnRH pulses in normal men. These data suggest an explanation for the patterns of LH and FSH responses to GnRH seen during spontaneous sexual maturation in males. During normal development the rising plasma T inhibits pituitary FSH secretion, so that FSH responses remain small and the marked FSH secretion seen in IGD patients does not occur.