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Biomedical subjects

P Eneroth

Publications and source records attributed to P Eneroth.

At least 343 records · Page 19Linked to original sources

Side chain hydroxylation of cholesterol, campesterol and beta-sitosterol in rat liver mitochondria.

The extent of the side chain hydroxylation of cholesterol, campesterol (24 alpha-methylcholesterol), and beta-sitosterol (24 alpha-ethylcholesterol) in rat liver mitochondria has been compared. Two beta-sitosterol metabolites, tentatively identified by liquid chromatography, thin-layer chromatography, gas-liquid chromatography, combined with radioactivity detection, and gas-liquid chromatography-mass spectrometry as the 26- and 29-hydroxy derivatives, were formed in the proportion 1:1. The sum of 26-hydroxy- and 29-hydroxy-beta-sitosterol obtained amounted only to about one-fourth of the yield of 26-hydroxycholesterol. Campersterol appeared to give rise only to 26-hydroxycampesterol (tentatively identified), which was formed in similar yields as 26-hydroxycholesterol (0.2-0.4%). The formation of 29-hydroxy-beta-sitosterol but not of 28-hydroxycampesterol indicates that the omega-hydroxylation of the steroid side chain is dependent on the length of the side chain. Cholesterol gave rise to identifiable amounts of a 25-hydroxy derivative but the formation of 25-hydroxy derivatives of beta-sitosterol and campesterol could not be established with certainty. 24-hydroxycholesterol was also found to be formed in the mitochondrial system. The ratio between the yields of 26- and 25-hydroxychoelsterol ranged between 2 and 3, and that between 26- and 24-hydroxycholesterol was about 10.

Animals↗

Early pregnancy interruption by 15 (S) 15 methyl prostaglandin F2alpha methyl ester.

Suppositories of 15-methyl PGF2alpha methyl ester in triglyceride were administered vaginally to 75 women in whom 31 to 49 days had elapsed since their last menstrual period. Three or four suppositories of 0.5, 1.0, or 1.5 mg were given at intervals of 3 hours. Pregnancy was later confirmed in 63 of the women. In the pregnant women vaginal bleeding usually started 3 to 6 hours after the initiation of therapy and continued for 10 to 14 days. Patients were followed for 2 to 4 weeks with serial measurement of serum progesterone and hCG. There were no failures in the trial, but in 2 cases the treatment resulted in incomplete abortion. In 2 other patients curettage was performed due to prolonged bleeding, but histologic examination revealed no remaining signs of pregnancy. Gastrointestinal side effects were well within acceptable limits, and no serious complications occurred. Clinical signs of pelvic inflammatory disease were not found. The vaginal use of 15-methyl PGF2alpha methyl ester seems promising as a reliable outpatient nonsurgical self-administered procedure for termination of early pregnancy.

Abortion, Incomplete↗

Plasma cortisol levels in human fetus during parturition.

In several mammalian species, the fetal adrenal cortex plays an important role in the spontaneous onset of labor. No conclusive evidence has yet been presented that a similar mechanism is active in humans. Although in some previous studies the cortisol concentration in human cord blood has been found higher after spontaneous labor than after induced labor, it has not been possible to determine whether this rise in the fetal cortisol level precedes the onset of parturition or is a consequence of labor. In the present study, starting at the earliest possible stage of labor, fetal scalp blood samples were taken sequentially during 16 spontaneous and 13 induced vaginal deliveries. Cortisol levels in these 2 goups of samples were compared with each other and also with cord blood cortisol levels in 11 patients undergoing elective cesarean section. The initial fetal cortisol levels did not differ between groups with different modes of labor onset. A pronounced rise of plasma cortisol levels occurred during labor in simultaneously sampled maternal and fetal blood. These results do not support the concept of a role for the fetal adrenal cortex in the initiation of labor in humans; they invalidate the use of cortisol concentration in cord blood for the estimation of prelabor fetal cortisol level. The origin of the cortisol surge in fetal plasma during labor and also whether the fetal adrenocortical function responds to the stress of labor are discussed. It is concluded that the rise of fetal cortisol levels during labor might mainly be a reflection of the maternal response to stress.

Amniotic Fluid↗

The effect of infusions with two analogues of prostaglandin F2alpha on corpus luteum function.

With the exception of one volunteer given the prostaglandin during ovulation, a transient decline in progesterone during the infusion was observed with both compounds. It is likely that the marked declines that were observed cannot be attributed solely to diurnal variation. Although the menstrual cycle was shortened in some cases after the infusion, this was not well-correlated with the acute effects seen at the time of infusion. Under the experimental conditions of this study, neither analogue appeared to be luteolytic. However, infusions with both compounds did alter serum progesterone transiently. It seems likely that both compounds do exert a potent effect on the corpus luteum and may in fact be luteolytic when given at some other time in the menstrual cycle.

Adult↗

Prostaglandin levels in peripheral plasma during the reproductive cycle.

The levels of the major plasma metabolite of PGF2alpha, 15-keto-13,14-dihydro-PGF2alpha, were followed in peripheral venous plasma during the reproductive cycle in three species, viz., the ovine, bovine, and human species. In the sheep and cattle low levels were encountered during the major part of the estrous cycle. During the last days of the cycle high levels of the prostaglandin metabolite were found, coinciding with the decrease in progesterone production. The human menstrual cycle was characterized with respect to some plasma steroids and peptide hormones. The prostaglandin metabolite levels were low throughout the cycle, generally ranging between 30 and 70 pg/ml. No significant variation in the prostaglandin production could be seen during the menstrual cycle.

Animals↗

Sex-dependent prepubertal gonadotrophin surges in the rat.

The concentrations of LH and FSH were measured by radioimmunoassay in sera from immature male and female rats of various ages. Fairly high levels of FSH were found in both sexes at birth but lh was not detected. FSH peaks appeared in the male at 13 and 19 days of age and in the female at 13 and 17-19 days of age. LH was undetectable in the male before 12 days of age, rose to a peak (440 plus or minus 60 (S.D.) ng/ml) at 13 days of age and fell below the detection level again between 15 and 25 days of age. A further increase then occurred which almost reached adult levels. LH was first detectable in the female rat at 11 days of age with a peak value of 130 plus or minus 35 ng/ml at 12 days. The hormone was undetectable on days 14 and 15, rose to a second peak on day (148 plus or minus 56 ng/ml), and was again absent between 19 and 25 days of age. The concentration rose, as in the male, between days 25 and 28 to a level similar to that of the adult. The results show sexual differences in prepubertal gonadotrophin surges. The LH peak at 12-13 days in both sexes appears to be light-dependent. The FSH peak at this time was affected by light but was not strictly light-dependent.

Age Factors↗

Formation and metabolism in vitro of 5,6-epoxides of cholesterol and beta-sitosterol.

The formation of 5alpha,6alpha- and 5beta,6beta-epoxides of cholesterol and beta-sitosterol in rat liver subcellular fractions has been studied. The results show that the epoxidation seems to occur only in connection with the nonspecific tissue oxidation of the sterols. The beta-epoxides were formed in three- to fourfold excess over the alpha-epoxides. Both cholesterol epoxides were efficiently converted by a microsomal hydrolase into the 3beta,5alpha,6beta-triol. The conversion was less extensive with beta-sitosterol epoxides, especially the beta-epoxide. The possible biological significance in the formation of the sterol epoxides and the triols was evaluated by their ability to inhibit the microsomal cholesterol 7alpha-hydroxylase. Only the cholesterol epoxides and especially the beta-epoxide were active in this respect.

Animals↗

Studies on the formation of C7-oxygenated cholesterol and beta-sitosterol metabolites in cell-free preparations of rat liver.

The microsomal fraction and the 18,000 g supernatant fluid obtained from livers from normal rats, cholestyraminetreated rats, or from rats with a bile fistula have been used to compare the 7alpha-hydroxylation of [4-(14)C]cholesterol and beta-[4-(14)C]sitosterol (24alpha-ethyl-cholesterol). It was not possible to increase the specific formation of 7alpha-hydroxy-beta-sitosterol above 0.05% with any of the preparations. This conversion was less than 1% of that found for cholesterol. The inhibitory effect of added 7-oxo- and 7beta-hydroxy-beta-sitosterol on the 7alpha-hydroxylation of cholesterol was found to be much less than that of the corresponding cholesterol compounds. 7alpha-Hydroxy-beta-sitosterol was without effect. It is concluded that the activity of the cholesterol 7alpha-hydroxylase is dependent upon the structure of the steroid side chain.

Animals↗