S. Dell'Acqua

Oxytocin receptor in human fetal membranes at term and during labor.

Human fetal membranes, taken from 30 patients submitted to caesarean section during the final stages of gestation and labor, were examined in order to evaluate the presence and characteristics of the oxytocin receptor. The presence of oxytocin receptors in human fetal membranes, both in the amnion and in the chorion-decidua, was demonstrated in this study. The receptor binding to oxytocin showed a significant increase during early and advanced labor compared with before the onset of labor. When the pre-labor level was taken as the normalized form (control = 100) the increase with respect to the control (10 cases) for the amnion in early labor (2.27 times +/- 0.11, mean +/- SEM, P less than 0.001, 10 cases) and in advanced labor (2.53 times +/- 0.15, 10 cases, P less than 0.001) was highly significant. In the chorion-decidua the increase was 1.61 times +/- 0.09, P less than 0.001 in early labor and 1.66 times +/- 0.19, P less than 0.001 in advanced labor. Scatchard analysis showed a single receptor site for oxytocin in amnion and chorion decidua. The dissociation constant (Kd) did not change during the various stages of labor; the mean values found were 0.228 +/- 0.02 (mean +/- SEM) nM in the amnion and 0.193 +/- 0.03 nM in the chorion-decidua respectively. These findings suggest that human fetal membranes are target organs for oxytocin and that they might play a role in the onset of labor through an increase of receptor binding.

Effect of naloxone on fetal behavior near term

Fetal behavior was studied after intravenous administration of either 0.4 mg of naloxone or an equal volume of saline solution in 54 healthy pregnant women near term. The number, duration, and amplitude of fetal heart rate accelerations increased after naloxone injection. The incidence of both gross fetal body movements and fetal breathing movements increased, especially in the first hour after naloxone administration. The distribution of fetal behavioral states was modified with a prevalence of active sleep and active awake states compared to the quiet sleep state. These data suggest that endorphins could be involved in the modulation of fetal behavior.

In Vitro effects of β-interferon on steroid receptors and prostaglandin output in human endometrial adenocarcinoma☆

The effect of natural beta-interferon (beta-IFN) on steroid receptor levels and output of prostaglandins (PGs) was investigated in human endometrial cancer. beta-IFN determines in endometrial adenocarcinoma explants an increase of cytosolic estradiol (ER) and progesterone (PR) receptors at concentrations ranging from 10 to 1000 IU/ml of culture medium. Only cases in which there was an enhancement of at least 50% with respect to control values were considered. Low concentrations of beta-IFN (10 IU/ml of culture medium) produce an enhancement of ER in 60% and of PR in 42% of cases, while higher concentrations of beta-IFN (1000 IU/ml of culture medium) produce an enhancement of ER in 32%, and of PR in 82% of cases. Since PGs are involved in proliferation control in a large variety of tumors, we evaluated the ratio between PGF2-alpha and PGE2 levels in culture medium. This ratio increased, in our experimental model, after treatment with 10 and 1000 IU/ml of beta-IFN in 38% and 58% of cases respectively. Our data suggest that beta-IFN could affect cellular hormone sensitivity through a modification of ER and PR and it can also determine a variation of PG output in human endometrial cancer.

Androgen binding in human fetal amnion

Human fetal amnion cytosol obtained at term is able to bind specifically [3H]testosterone. The cytosol (105,000 g supernatant) from human amnion was used after a 30 min treatment with dextran-coated charcoal and incubated with increasing concentrations of [3H]testosterone, [3H]dihydrotestosterone, [3H]methyltrienolone for 2 h at 4 degrees C and for 16 h at 15 degrees C. To avoid any possible contamination of sex hormone binding globulin we used a Sepharose 4B column. Scatchard plot analysis of the data after incubation at 4 degrees C for 2 h showed that the amnion possesses high affinity (Kd = 0.62 +/- 0.20 nM) and low capacity (95.0 +/- 21.1 fmol/mg protein) binding sites for [3H]testosterone. After incubation at 15 degrees C for 16 h, we obtained a high affinity (Kd = 0.29 +/- 0.14 nM), low capacity (49.5 +/- 12.8 fmol/mg protein) and a low affinity (Kd = 5.55 +/- 2.55 nM), high capacity (181.7 +/- 20.8 fmol/mg protein) binding sites for [3H]testosterone. The values of Kd, calculated from Scatchard plot analysis were 1.03 +/- 0.7 nM with 20.2 +/- 10.4 fmol/mg protein and 1.97 +/- 1.06 nM with 55.6 +/- 15.9 fmol/mg protein for [3H]methyltrienolone and [3H]dihydrotestosterone respectively. These findings suggest that human fetal amnion cytosol at term contains a specific binding protein for androgens.

Hormone receptors and enzymatic activities in human endometrial adenocarcinoma.

The hormone sensitivity of endometrial carcinoma is related to the presence of steroid hormone receptors. The determination of progesterone receptors has been proposed in order to predict clinical prognosis and to aid treatment selection. The integrity of the hormone receptor system and postreceptoral events in tumors is essential to endocrine therapy response. Nevertheless, although hormone receptors are present in a large number of endometrial carcinomas, only 30% of cases respond to hormone therapy. In some neoplasms the receptors can be present, but not functioning, or else neoplastic transformation could have induced alterations in processes after hormone-receptor interaction.