Estrogenic status influences nitric oxide-regulated TNF-alpha release from human peripheral blood monocytes.
Cytokines and nitric oxide (NO) have been implicated in bone loss caused by estrogen deficiency. Here we evaluated the effect of nitric oxide synthase (NOS) inhibitors on the bone particle resorbing activity and TNF-alpha release of cultured peripheral blood monocytes (PBM) obtained from 10 premenopausal (PreM) and 10 postmenopausal (PostM) women. Gonadal status (menopause < 3 yr) was assessed by FSH and estradiol. Bone alkaline phosphatase and N-Telopeptide were significantly increased in PostM. Significant differences between PreM and PostM women were observed in bone mineral density of lumbar spine. The bone particle resorbing activity of PBM cultured in the presence of L-arginine-methyl ester (NAME) or aminoguanidine, NOS inhibitors, was determined by (45)Ca release from rat bone labeled particles. TNF-alpha release was assayed in supernatants by ELISA. (45)Ca release was higher in PostM (p < 0.01) and was enhanced by NAME (p < 0.02). Furthermore, TNF-alpha release from PBM was significantly higher in PostM (p < 0.01). Aminoguanidine significantly increased TNF-alpha release in PreM. Based on these findings and on the evidence that estrogen stimulates NOS, we suggest that estrogen withdrawal may reduce the inhibitory effect of NO on TNF-alpha release. Thus, this increased production of TNF-alpha could contribute to the increased postmenopausal bone turnover.
Schurman
L
L
Servicio de Endocrinologia, Hospital Francés, La Rioja 951, Buenos Aires 1221, Argentina. lschurman@connmed.com.ar
Sedlinsky
C
C
Mangano
A
A
Sen
L
L
Leiderman
S
S
Fernandez
G
G
Theas
S
S
Damilano
S
S
Gurfinkel
M
M
Seilicovich
A
A
D000328:Adult; D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology; D001842:Bone and Bones / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004967:Estrogens / Q000097:blood*; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D017698:Postmenopause / Q000097:blood; D017697:Premenopause / Q000097:blood; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004791:Enzyme Inhibitors; D004967:Estrogens; D006146:Guanidines; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C004479:pimagedine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester