Inhibition of luteinizing hormone secretion by testosterone in men requires aromatization for its pituitary but not its hypothalamic effects: evidence from the tandem study of normal and gonadotropin-releasing hormone-deficient men.

Détails

ID Serval
serval:BIB_F8FDBAAB14FF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Inhibition of luteinizing hormone secretion by testosterone in men requires aromatization for its pituitary but not its hypothalamic effects: evidence from the tandem study of normal and gonadotropin-releasing hormone-deficient men.
Périodique
Journal of Clinical Endocrinology and Metabolism
Auteur(s)
Pitteloud N., Dwyer A.A., DeCruz S., Lee H., Boepple P.A., Crowley W.F., Hayes F.J.
ISSN
0021-972X (Print)
ISSN-L
0021-972X
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
93
Numéro
3
Pages
784-791
Langue
anglais
Notes
Publication types: Journal Article
Résumé
CONTEXT: Studies on the regulation of LH secretion by sex steroids in men are conflicting.
OBJECTIVE: Our aims were to determine the relative contributions of testosterone (T) and estradiol (E2) to LH regulation and localize their sites of negative feedback.
DESIGN: This was a prospective study with three arms.
SETTING: The study was conducted at a General Clinical Research Center.
PATIENTS OR OTHER PARTICIPANTS: Twenty-two normal (NL) men and 11 men with GnRH deficiency due to idiopathic hypogonadotropic hypogonadism (IHH) participated.
INTERVENTION: Medical castration and inhibition of aromatase were achieved using high-dose ketoconazole (KC) for 7 d with 1) no sex steroid add-back; 2) T enanthate 125 mg im starting on d 4; or 3) E2 patch 37.5 microg/d starting on d 4. Blood sampling was performed every 10 min for 12 h at baseline, overnight on d 3-4 and d 6-7.
MAIN OUTCOME MEASURES: Mean LH levels, LH pulse amplitude, and GnRH pulse frequency were assessed at baseline, d 3-4, and d 6-7.
RESULTS: In NL men, KC caused a 3-fold increase in mean LH on d 3-4, which was stable on d 6-7 with no add-back. Addition of T reduced LH levels (34.6+/-3.9 to 17.4+/-3.6 IU/liter, P<0.05) by slowing GnRH pulse frequency (13.3+/-0.4 to 6.7+/-1.0 pulses/12 h, P<0.005). LH amplitude increased (6.9+/-1.0 to 12.1+/-1.4 IU/liter, P<0.005). E2 add-back suppressed LH levels (36.4+/-5.6 to 19.0+/-2.4 IU/liter, P<0.005), by slowing GnRH pulse frequency (11.4+/-0.2 to 8.6+/-0.4 pulses/12 h, P<0.05) and had no impact on LH pulse amplitude. In IHH men, restoring normal T levels caused no suppression of mean LH levels or LH amplitude. E2 add-back normalized mean LH levels and decreased LH amplitude from 14.7+/-1.7 to 12+/-1.5 IU/liter (P<0.05).
CONCLUSIONS: 1) T and E2 have independent effects on LH. 2) Inhibition of LH by T requires aromatization for its pituitary, but not hypothalamic effects. 3) E2 negative feedback on LH occurs at the hypothalamus.
Mots-clé
Adult, Aromatase Inhibitors/pharmacology, Estradiol/metabolism, Estradiol/pharmacology, Feedback, Physiological, Gonadotropin-Releasing Hormone/deficiency, Humans, Hypogonadism/metabolism, Hypothalamus/drug effects, Ketoconazole/pharmacology, Luteinizing Hormone/antagonists & inhibitors, Luteinizing Hormone/secretion, Male, Pituitary Gland/drug effects, Prospective Studies, Testosterone/metabolism, Testosterone/pharmacology
Pubmed
Création de la notice
03/12/2014 16:32
Dernière modification de la notice
03/03/2018 22:53
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