Role of interferon-alpha in arachidonic acid metabolism by the rat uteri from spayed animals: effect of 17 beta-estradiol.
Interferon-like trophoblastic proteins modulate prostaglandin (PG) synthesis from endometrium in early ovine and bovine pregnancy. We attempted to explore the effect of interferon (IFN)-alpha in the isolated rat uterus from ovariectomized animals on the metabolism of labelled arachidonic acid (AA). The experiments were performed with uterine preparations isolated from spayed rats treated or untreated with 17 beta-estradiol prior to sacrifice. The pre-incubation of uterine tissue isolated from ovariectomized rats with three different doses (4, 150 and 300 IU/ml) of IFN-alpha decreased the radioconversion of [14C]AA into 6-keto PGF1 alpha, PGF2 alpha and PGE2, whereas the formation of thromboxane B2 (TXB2) decreased after treatment with 4 IU/ml of INF-alpha but was augmented with 150 and 300 IU/ml. The three doses used diminished the synthesis of 5-hydroxyeicosatetraenoic acid (5-HETE) and increased the production of 12-HETE. We also studied the synthesis of uterine products of cyclooxygenase and lipoxygenase in uterine tissue from ovariectomized rats injected with 17 beta-estradiol and preincubated with IFN-alpha. We found that the three doses of IFN-alpha diminished the production of 6-keto-PGF1 alpha, PGE2, PGF2 alpha and TXB2 as well as 5-HETE and 12-HETE. These findings show that IFN-alpha modifies the basal synthesis of PGs from uterine tissue. Ovine and bovine trophoblastic protein prevents luteolysis by inhibiting the synthesis of PGF2 alpha. On the other hand, IFN-alpha shows 70% homology with ovine trophoblastic protein and binds to the same receptor. The results of the present study suggest that IFN-alpha may also act in the rat as a luteotrophic agent.
Motta
A B
AB
Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina (CONICET), Buenos Aires, Argentina.
Franchi
A M
AM
Gimeno
M F
MF
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D010052:Ovariectomy; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013931:Thromboxanes / Q000096:biosynthesis; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D016898:Interferon-alpha; D011453:Prostaglandins; D013931:Thromboxanes; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D004958:Estradiol; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid