Disaturated phosphatidylcholine as a fetal lung maturity test: lack of interference by seminal ejaculate as a contaminant in vaginally pooled amniotic fluid samples.

Seminal ejaculates obtained from four men were added to amniotic fluid pools. Lecithin/sphingomyelin ratios in amniotic fluid were significantly lowered in the presence of small amounts of contaminating semen. In contrast, the determination of disaturated phosphatidylcholine was not affected by the presence of this contaminant.

Effect of prenatal dexamethasone on immunoreactive 6-ketoprostaglandin F1 alpha levels in fetal rat lungs.

The effect of prenatal glucocorticoid treatment on levels of immunoreactive 6-ketoprostaglandin F1 alpha (PGF1 alpha) (the stable metabolite of prostacyclin) was studied in fetal rat lungs. During late gestation (20-22 days), levels of 6-keto-PGF1 alpha peaked at 21 days in offspring of control mothers. At a maternal dose of 0.2 mg/kg dexamethasone, maximal enhancement of fetal 6-keto-PGF1 alpha levels occurred at 20 days gestation. At a treatment dose of 0.4 mg/kg, however, dexamethasone increased fetal lung 6-keto-PGF1 alpha concentrations throughout late gestation. Because maturation of fetal lung is known to be delayed in males relative to females, we also studied the impact of sex of the fetus on levels of 6-keto-PGF1 alpha. Our results showed no statistically significant differences between females and males in any of the treatment groups at any of the gestational ages studied. These results suggest that prenatal dexamethasone enhances endogenous levels of 6-keto-PGF1 alpha in fetal rat lungs. Since prostacyclin may play important roles in fetal lung maturation and neonatal lung function, the effectiveness of prenatal glucocorticoid therapy for accelerating functional maturity of the fetal lung may in part be due to stimulation of prostacyclin synthesis.

Nuclear estrogen receptor and nonhistone chromosomal proteins in hormonal independency of murine breast cancers.

The capability of nuclear binding of cytosol estrogen receptors (ERc) was studied in GR mouse mammary tumors during their alteration of hormonal dependency through serial transplantations. Nuclei from GR mouse mammary tumors were incubated with uterine cytosol receptor complexes labeled with 125I-estradiol, and the amount of receptor binding in the 0.4 M KCl nuclear extracts was determined. The originally ERc-positive-hormone-dependent (type I) tumors were capable of nuclear receptor binding, while this function was markedly reduced in the evolved hormone-independent (type II) tumors, although the ERc content in the latter was still positive. The originally hormone-independent (ERc-negative, type III) tumors, however, retained the nuclear binding capability. It appears that the hormonal independency in type III tumors is due to a lack of ER, while in type II tumors it may be attributed to the loss of nuclear binding capability for receptor complexes. Nonhistone chromosomal proteins (NHCP) were analyzed by the 2-dimensional gel electrophoretic technique. A Mr 31,000 NHCP was present in 11 of 12 type I, and four of four type III tumors. Following serial transplantation of the type I tumors, this NHCP was either markedly diminished or not observed in all 14 type II tumors examined. Although it coincides with the capability of nuclear receptor binding, the biological function of this NHCP is still undefined and warrants further investigation.

Progesterone receptors in feline mammary adenocarcinomas.

Estradiol and progesterone receptors were measured in tumor cytosols from 3 intact and 4 neutered female cats with spontaneously occurring mammary adenocarcinomas. Serum from 2 of the intact cats which had been in estrus 4 and 4 to 6 weeks before tumor excision contained progesterone concentrations of 16.2 and 2.2 ng/ml, respectively; serum progesterone in the other cats was less than 2 ng/ml. Estradiol receptors were not detected in any cytosols. Progesterone receptors were detected in all of the cytosols, in concentrations ranging from 4.0 to 11.7 (mean = 7.2) fmol/mg of protein. Scatchard plot analysis of tumor cytosol from an 8th cat with mammary adenocarcinoma revealed presence of high affinity progesterone binding with a dissociation constant (Kd) of 3.47 nM. Tumor receptor content could not be correlated with stage of the estrous cycle nor with whether the cat was intact or neutered.

The effect of prenatal dexamethasone on fetal rat lung prostaglandin synthesis.

[14C]Arachidonic acid conversions were studied in homogenates of lungs from 20, 21, and 22 day fetuses with or without prenatal dexamethasone treatment. The major metabolites were in all cases 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), prostaglandin E2 (PGE2), and 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT). Prostaglandin F2 alpha (PGF2 alpha), prostaglandin D2 (PGD2), and thromboxane B2 (TxB2) were present in small amounts. Dexamethasone treatment significantly stimulated the conversion of [14C]-arachidonic acid in fetal lung homogenates to 6-keto-PGF1 alpha, PGE2, 12-HETE, and HHT, at 20 days gestational age. This effect was dependent on the dose of dexamethasone. These results suggest that dexamethasone accelerates the maturation of the enzymes involved in prostaglandin synthesis. Because dexamethasone is also known to inhibit phospholipase A2, further studies are required to determine the overall in vivo effect of prenatal dexamethasone therapy on fetal lung prostaglandin synthesis.