Dopamine in the nucleus accumbens: preferential increase of DA turnover by rat prolactin.
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Biomedical subjects
Publications and source records attributed to P Eneroth.
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The role of the fetal adrenal activity in the initiation of parturition in the human has been investigated. Women were studied in the last trimester of pregnancy during treatment with betamethasone for prevention of the idiopathic respiratory distress syndrome. Although betamethasone caused a considerable drop in the cortisol concentrations of fetal plasma and amniotic fluid, the time to spontaneous delivery in this group was similar to that in matched controls. Moreover, cortisol in fetal scalp blood at the onset of parturition in untreated women did not differ between those with spontaneous and those with induced labour. Evidence is given that increase of circulating cortisol in the fetus during the course of parturition predominantly reflects a rise in maternal cortisol under the influence of labour. The strain of labour seems to partly override the betamethasone-induced inhibition of maternal cortisol release. The possible ability of the fetal adrenals to respond to stimuli is illustrated by comparison of cortisol concentrations in cord plasma after various forms of complicated deliveries.
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In psychotic patients, levels of prolactin in cerebrospinal fluid (CSF) and plasma were determined by radioimmunoassay before and after 2 and 4 weeks of treatment with chlorpromazine (CPZ). CPZ was given in one of three randomly selected fixed doses: 200, 400 or 600 mg per day. Before treatment, low levels of immunoreactive prolactin-like material (PRL) were found in the CSF of most patients. The concentration in CSF was about 20% of the plasma level. In CSF but not in plasma, the pre-treatment level of PRL was significantly higher in women than in men. During CPZ treatment, the PRL levels in CSF as well as in plasma were significantly elevated in both sexes after 2 as well as 4 weeks. The elevation was significantly greater in women, and was similar at the two time intervals studied. There was a significantly positive relationship between the dose of CPZ and the PRL elevation in both body fluids in both men and women. Before treatment no significant correlation between the PRL levels in CSF and plasma in either sex could be observed. During treatment, there was a significant correlation between the change in PRL levels in CSF and plasma in both men and women. CPZ treatment did not increase the levels of total protein, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH) or oestradiol-(17-beta) in either the CSF or the plasma.
The effect of four different clonal pituitary tumors on hepatic steroid metabolism was studied in male and female rats and this effect was related to the secretion of prolactin, LH and FSH from the tumors. Tumors derived from the cell line C811RAP caused an alteration of the steriod metabolism to a completely female pattern in male rats whereas it had little effect on metabolism in female rats. This tumor cell line was the only one which appeared to secrete prolactin according to the observed level of this hormone in host serum. Furthermore, extract from C811RAP tumor tissue increased the 5alpha-reductase activity in cultured HTC CELLS. The other cell lines tested (C29RAP, C13RAP and C311RAP) did not appear to secrete prolactin but did have general effects on the hepatic steroid metabolism of both sexes. These effects could not be interpreted as changes towards a female or a male pattern of metabolism. When extract from C13RAP or C211RAP tumor tissue was assayed in the HTC cell system, small or insignificant effects on the 5alpha-reductase activity were observed. In conclusion, it appears that the C811RAP pituitary tumor cell line produces a factor(s) that in duces a female type of hepatic steroid metabolism in the rat. This factor does not seem to be produced by the other cell lines tested. Based on the clonal nature of the cells and the fact that the C811RAP cells also secrete prolactin, it is reasonable to suggest that the mammotrophs of the normal female pituitary are the cells that produce this factor.
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15(S) 15-methyl-PGF2alpha-methyl ester was administered as vaginal suppositories to terminate very early gestation in 16 outpatients who were thought to be pregnant. All patients received between 2.5 and 5.0 mg. of the prostaglandin compound. Pregnancy was confirmed later in 10 of the women. In these patients vaginal bleeding started 3 to 6 hours after the start of therapy and continued for an average of 8 days. By subjective assessment, the amount of bleeding during this time was equal to or slightly heavier than that of a normal menstruation for each woman. Patients were followed for 2 to 4 weeks with serial measurements of serum progesterone and HCG. There were no failures at early pregnancy interruption. Gastrointestinal side effects rarely were encountered; no serious complications occurred and no curettage had to be performed because of heavy bleeding. The vaginal use of the methyl ester of 15(S) 15-methyl-PGF2alpha for the termination of early pregnancy seems promising as a reliable and parctical outpatient procedure.
The influence of maternal corticosteroid administration on the cortisol concentration in fetal blood and amniotic fluid (AF) was studied in women receiving betamethasone for prevention of IRDS. Thirty-four pregnant women in danger of spontaneous or induced preterm delivery were treated with 12 mg. of betamethasone daily for 3 days. AF was obtained by amniocentesis on the day before and the day following the betamethasone treatment and by amniotomy at delivery; cord arterial and venous blood was taken at delivery. Corresponding samples were obtained from 17 pregnant control subjects. All samples were analyzed in duplicate for cortisol by radioimmunoassay. The basal AF cortisol level rose with gestational age. The AF cortisol concentration fell from the basal value of 24.5 +/- 1.8 to 5.4 +/- 0.4 ng. per milliliter 3 days after the start of treatment, and it remained low at delivery if the treatment-delivery time was less than 1 week. An almost significant positive correlation (r = 0.543) was found between the cortisol concentration in cord arterial blood and AF. The cortisol concentration in cord blood in the controls was 108.2 +/- 14.3 ng. per milliliter in the arteries and 106.4 +/- 18.6 ng. per milliliter in the vein. Also, the cord blood cortisol level was depressed in betamethasone had been given within one week before delivery. The multifactorial influence on cord blood cortisol level prevents interpretation of the results as support for the concept that the human fetal adrenal is involved in labor initiation. The duration of gestation was not altered by the betamethasone treatment. The analysis of cortisol in the easily accessible amniotic fluid is suggested for estimating the function of the fetal adrenal cortex.
15(S)15-methyl PGF2alpha methyl ester was self-administered vaginally to terminate pregnancy in 42 women in the 8-9th week of gestation. Ten patients received a total of 6 mg of the compound over 15 hours (Group I) while the remaining 32 patients received 5.5 mg of the prostaglandin compound during a shorter period of time or 9 hours (Group II). If parts of the conceptus were expelled during treatment, surgical intervention was excluded. All patients were followed closely after treatment with repeated serum HCG assays and clinical examinations. All patients in Group II and eight out of ten patients in Group I aborted following treatment. In 33 of the 42 patients, the serum HCG levels and the clinical course following the expulsion of the conceptus indicated that abortion was complete. Gastro-intestinal side effects were minimal if anti-diarrheic agents were given prophylactically. The incidence of uterine pain was variable but could in most cases be controlled by oral or rectal administration of analgetics. The results of this study suggest that the use of this compound for termination of pregnancy may be safely extended through the 9th week of gestation and in certain cases be an alternative to the normal operative procedure.
After transplantation of MtT/F4 pituitary tumor cells to male rats of the Fisher strain, the masculine type of hepatic steroid metabolism was changed into a feminine pattern of enzyme activities. Liver metabolism of steroid hormones in female rats was relatively unaffected following transplantation of pituitary tumor cells. Futhermore, extract from MtT/F4 tumors and "autonomous" pituitary tissue increased the 5alpha-reductase activity of hepatoma cells in the culture (HTC cells) at subsaturation concentrations of the substrate 4-androstene-3, 17-dione by decreasing the apparent Km of the enzyme. It is concluded that the pituitary tumor (in accord with the secretion from an "autonomous" pituitary gland) secretes "feminotropin," a novel hypophyseal principle that probably is an important regulator of hepatic steriod metabolism. It is suggested that pituitary tumor tissue of the MtT/F4 type could be used as source of feminotropin in purification studies.
Steadily progressive improvement in the diagnostic and therapeutic management of malignant trophoblastic disease has occurred over the last few decades. The most important diagnostic aid is the determination of serum HCG by sensitive radioimmunoassay which allows the detection of minute amounts of the hormone and permits discrimination between LH and HCG. Therapeutic advances include the use of combinations of different cytostatic drugs which have increased the cure rate from approximately 50% to a range of 80-95% (1, 2, 3, 4, 5, 6, 7). Malignant trophoblastic disease is rare in the Scandinavian countries which effectively limits opportunities to acquire experience within individual centers. However, a series of 23 cases has been collected at the Karolinska Hospital during the last 10 years. Patients who developed resistance against methotrexate were successfully treated by a combination of an alkylating agent melphalan (Alkeran), actinomycin D and methotrexate. In some cases this modification of a triple-therapy regimen has turned out to be life-saving.