Age disrupts androgen receptor-modulated negative feedback in the gonadal axis in healthy men

作者：Veldhuis Johannes D^*; Takahashi Paul Y; Keenan Daniel M; Liu Peter Y; Mielke Kristi L; Weist Suanne M

来源：American Journal of Physiology - Endocrinology And Metabolism, 2010, 299(4): E675-E682.

DOI：10.1152/ajpendo.00300.2010

• leuteinizing hormone
• testosterone
• pulsatile
• secretion
• human
• approximate entropy

Veldhuis JD, Takahashi PY, Keenan DM, Liu PY, Mielke KL, Weist SM. Age disrupts androgen receptor-modulated negative feedback in the gonadal axis in healthy men. Am J Physiol Endocrinol Metab 299: E675-E682, 2010. First published August 3, 2010; doi: 10.1152/ajpendo.00300.2010.-Testosterone (T) exerts negative feedback on the hypothalamo-pituitary (GnRH-LH) unit, but the relative roles of the CNS and pituitary are not established. We postulated that relatively greater LH responses to flutamide (brain-permeant antiandrogen) than bicalutamide (brain-impermeant antiandrogen) should reflect greater feedback via CNS than pituitary/peripheral androgen receptor-dependent pathways. To this end, 24 healthy men ages 20-73 yr, BMI 21-32 kg/m(2), participated in a prospective, placebo-controlled, randomized, double-blind crossover study of the effects of antiandrogen control of pulsatile, basal, and entropic (pattern regularity) measurements of LH secretion. Analysis of covariance revealed that flutamide but not bicalutamide 1) increased pulsatile LH secretion (P = 0.003), 2) potentiated the age-related abbreviation of LH secretory bursts (P = 0.025), 3) suppressed incremental GnRH-induced LH release (P = 0.015), and 4) decreased the regularity of GnRH-stimulated LH release (P = 0.012). Furthermore, the effect of flutamide exceeded that of bicalutamide in 1) raising mean LH (P = 0.002) and T (P = 0.017) concentrations, 2) accelerating LH pulse frequency (P = 0.013), 3) amplifying total (basal plus pulsatile) LH (P = 0.002) and T (P < 0.001) secretion, 4) shortening LH secretory bursts (P = 0.032), and 5) reducing LH secretory regularity (P < 0.001). Both flutamide and bicalutamide elevated basal (nonpulsatile) LH secretion (P < 0.001). These data suggest the hypothesis that topographically selective androgen receptor pathways mediate brain-predominant and pituitary-dependent feedback mechanisms in healthy men.

• 出版日期2010-10
• 单位河北医科大学