Gender differences in response to chronic treatment with 17ß-oestradiol and 17ß-aminoestrogen pentolame on hemostasis in rats.

OBJECTIVES: This work evaluated chronic treatment with 17ß-oestradiol (E2) and 17ß-aminoestrogen pentolame (AEP) on prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen concentration (FIB). Male (M) and ovariectomized (Ovx) Wistar rats were used to explore gender differences in the pharmacological response. MATERIALS AND METHODS: Rats (n=12-18) were treated every third day during three months with E2 (1, 10, 100 µg/kg), AEP (1, 10, 100, 500 µg/kg) or vehicle (propylenglycol 1 ml/ kg). PT, aPTT, TT, and FIB were measured using standardized techniques. RESULTS: Chronic treatment with E2 in male rats increased PT (4-7%; P<0.05), decreased aPTT (9%; 100 µg/kg; P<0.05) and decreased TT (5% at 100 µg/Kg; P<0.05). Chronic treatment with E2 in ovariectomized female rats decreased PT (3-4%; P<0.05), did not induce significant changes on aPTT and decreased TT in a dose dependent manner (12-27%; P<0.05). Chronic treatment with AEP in male rats did not alter PT, increased aPTT in a dose dependent manner (5-16%; P<0.05), and decreased TT (5%; 500 µg/Kg; P<0.05) while in female ovariectomized rats it decreased PT (5-9%; P<0.05), increased aPTT (8-13%; P<0.05) and decreased TT (6-13%; P<0.05). E2 and AEP decreased FIB in M and Ovx animals. Decreases in FIB by E2 were more pronounced in male (15-18% P<0.05) than in ovariectomized rats (10-14% P<0.05). E2 showed more potency than AEP, lowering FIB at 1 and 10 µg/kg doses. Both estrogens decreased FIB in ovariectomized animals (E2, 10-14%, P<0.05; AEP, 9% P<0.05) and were reverted by increasing dosage. CONCLUSIONS: Gender influenced response to chronic treatment with E2 and AEP on hemostatic parameters. PT and aPTT were the most affected parameters, demonstrating non-equivalence in the pharmacological response of M and Ovx rats.

Influence of chronic prenatal and postnatal administration of naltrexone in locomotor activity induce by morphine in mice

The influence of chronica pre- and postnatal naltrexone exposure on the sensitivity of off spring to the locomotor effects of morphine was investigated i C-57 Black mice. Pregnant mice were injected subcutaneously (sc) with either saline (0.1 ml/10 g) or naltrexone (10 mg/kg) twice daily during gestation and throughout lactation, 21 days postpartum. One, three and seven weeks after bith, male offspring were tested for locomotor activity. At 7 weeks of age, dose-response curves were obtained with morphine (10, 31.6, and 100 mg/kg) and amphetamine (0.31, 10 and 31.6 mg/kg) in naltrexone-pretreated and in saline-treated animals. Naltrexone exposure during gestation and lactation resulted in an augmented sensitivity of offspring to the locomotor activity increasing effects of morphine. In these animals, the dose-response relationship for the effect of morphine on locomotor activity was displaced to the left about threefold. In contrast, naltrexone exposure did not alter the sensitivity of offspring to amphetamine. It was also found that ofsspring of naltrexone-treated animals have significantly greater spontaneous locomotor activity than that of the offspring of saline treated mothers. The increased locomotor activity persisted for at least 4 weeks after the last injection of naltrexone. These findings indicate that chronic opioid receptor blockade during gestation and early portnatal development induces supersensitivity to the locomotor effects of morphine and is associated with long-lasting behavioral alterations

Relaxant action of androgens, progestins and corticosteroids on the isolated ileum of the guinea pig

La acción de tres diferentes clases de derivados de la progesterona fueron probados sobre las contracciones espontáneas del íleon aislado de cobayo. Los resultados mostraron que este tejido es muy sensible a la acción de los esteroides. Se observó una marcada relajación que fue dependiente de la dosis y diferente para cada compuesto. Esta diferencia fue asociada a la estructura molecular del esteroide. Así, las progestinas 5ß-reducidas fueron las más potentes, seguidas de los andrógenos 5 alfa y 5ß-reducidos. Los compuestos 4-en, 17 alfa-OH-progesterona y los corticosteroides, fueron los más bajos en potencia. La 5alfa-pregnandiona y los pregnandioles fueron prácticamente inefectivos. La gran sensibilidad del músculo liso del íleon permite postular a este órgano como blanco de esteroides. Es posible que en algunas circunstancias fisiológicas, como podría ser el embarazo, los trastornos de motilidad intestinal observados en este estado estén asociados al incremento notable de esteroides circulantes