title: In men, peripheral estradiol levels directly reflect the action of estrogens at the hypothalamo-pituitary level to inhibit gonadotropin secretion.
abstract: BACKGROUND
  Estradiol inhibits gonadotropin release in men by an action at the hypothalamus and pituitary. Because of the tissue-specific regulation of aromatase, peripheral estradiol levels may not reflect brain estradiol concentrations.
  
  
  OBJECTIVE
  We evaluated whether local aromatization of testosterone in the hypothalamus or pituitary is important for gonadotropin release and to what extent circulating estrogens affect gonadotropin levels and peripheral testosterone levels. DESIGN, SUBJECTS, AND INTERVENTIONS: We suppressed aromatase activity in 10 young healthy men with letrozole 2.5 mg once daily, restored plasma estradiol levels with estradiol patches (100 microg/d for the first week, 50 microg/d the second week, 25 microg/d the third week, and no estradiol patch the fourth week) and measured plasma testosterone, estradiol, LH, FSH, and SHBG levels.
  
  
  RESULTS
  The mean estradiol and testosterone levels during the study ranged between 68.6 +/- 38.3 and 12.6 +/- 7.21 pg/ml for estradiol and 179 +/- 91 and 955 +/- 292 ng/dl (mean +/- sd) for testosterone. Levels of testosterone, LH, and FSH were inversely related to peripheral estradiol levels. During letrozole use, the mean plasma estradiol level needed to restore testosterone, LH, and FSH levels to baseline levels was not significantly different from the baseline mean estradiol level.
  
  
  CONCLUSIONS
  Local aromatization of testosterone in the hypothalamo-pituitary compartment is not a prerequisite for expression of the inhibitory action of estrogens on gonadotropin secretion in men. Peripheral estradiol levels directly reflect the inhibitory tone exerted by estrogens on gonadotropin release and are a major determinant of peripheral testosterone, LH, and FSH levels.
authors.affiliation: Department of Endocrinology, VU University Medical Center, de Boelelaan 1117, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: Garrett
authors.initials: G
authors.lastname: Raven
authors.forename: Frank H
authors.initials: FH
authors.lastname: de Jong
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Kaufman
authors.forename: Willem
authors.initials: W
authors.lastname: de Ronde
mesh_terms: D000328:Adult; D047072:Aromatase Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000096:biosynthesis / Q000097:blood / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000097:blood; D006062:Gonadotropins / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D000077289:Letrozole; D016014:Linear Models; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood; D014230:Triazoles / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D006062:Gonadotropins; D009570:Nitriles; D012738:Sex Hormone-Binding Globulin; D014230:Triazoles; D013739:Testosterone; D004958:Estradiol; D000077289:Letrozole; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone