Tumor necrosis factor-alpha inhibits ovulation and steroidogenesis, but not prostaglandin production in the perfused rat ovary.
OBJECTIVE
We tested the null hypothesis that tumor necrosis factor-alpha (TNF-alpha) does not decrease ovulation, estradiol and progesterone production, or prostaglandin (PG) E2, PGF2alpha, or 6 keto-PGF1alpha production in the open bursa rat ovarian perfusion model.


METHODS
Experimental animals were controlled for age, weight, litter, and pregnant mare's serum gonadotropin (PMSG) aliquot. Female Sprague-Dawley rats, 26-27 days old, were injected with 25 IU PMSG. Forty-eight hours later, the right ovary was dissected, the bursa removed, and the specimen placed in the perfusion chamber with defined media. Luteinizing hormone and isobutylmethylxanthine were given as an ovulatory trigger. Test perfusions also received TNF-alpha in 0.8-nmol/L, -pmol/L, and -fmol/L doses. Samples were collected at 0, 1, 3, 5, 7, 10, and 20 hours. Ovulations were counted at 20 hours. Steroids and PGs were measured.


RESULTS
The addition of TNF-alpha to the rat ovarian perfusion model resulted in a dose-dependent decrease in ovulations (mean +/- standard deviation): 16.14 +/- 6.2 in controls (n = 7) versus 2.38 +/- 3.4 with TNF-alpha 0.8 nmol/L (n = 7), and 4.3 +/- 1.5 with TNF-alpha 0.8 pmol/L (n = 3), both P < .001. Tumor necrosis factor-alpha also inhibited estradiol (P < .005) and progesterone production (P < .05) throughout, but produced no significant changes in PG production.


CONCLUSIONS
Tumor necrosis factor-alpha inhibits ovulation in a dose-dependent fashion, and inhibits estradiol and progesterone production without altering PG production in the open bursa rat ovarian perfusion model.
Hales
H A
HA
Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Peterson
C M
CM
Mitchell
M D
MD
Jones
K P
KP
Hatasaka
H H
HH
Poulson
A M
AM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000494:pharmacology; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D010060:Ovulation / Q000187:drug effects*; D010477:Perfusion; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013256:Steroids / Q000096:biosynthesis*; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D006064:Gonadotropins, Equine; D010726:Phosphodiesterase Inhibitors; D011453:Prostaglandins; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine