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[Effects of lead administered during pregnancy to C57B1 mice].

Treatment of female mice with high doses of lead from different times of the gestation, induces abortion or retardation of growth of the embryos. When it is given from birth, it provokes important mortality in the youngs and a retardation of the postnatal growth. In most cases, lead administered from the first day of gestation delays slightly the development of the embryo and inhibits its implantation. It seems that a deficiency in the plasmatic progesterone levels is directly implied in this inhibition.

Abortion, Spontaneous↗

Thrombotic thrombocytopenic purpura and related disorders.

This article provides us with background information on the disease. Clinical features, variants and classification, laboratory findings, and pathology are discussed. Knowledge of the disease's pathogenesis has increased recently and specific causes discussed are predisposing factors, triggering agents, endothelial damage, defective PGI2 bioavailability, FVIII/vWF multimeric structure abnormalities, platelet activation, and hemolytic anemia. Proposed specific therapies discussed are steroids, heparin, antiplatelet agents, prostacyclin, splenectomy, immunosuppressive agents, plasma infusion, and plasma exchange.

Adolescent↗

Elevated prolactin levels in oral contraceptive pill-related hypertension.

Twenty women whose blood pressure became elevated during oral contraceptive treatment had higher serum prolactin levels (31 +/- 5.3 microgram/liter) than did 20 normotensive pill takers (16.1 +/- 1.8 microgram/liter) and 20 women who were not taking the pill (14 +/- 1.1 microgram/liter), and the higher level was maintained (30 +/- 3.5 microgram/liter) after the pill was discontinued and blood pressure had become normal. This increase in prolactin levels was not related to differences in age or mode of treatment, and it is thought to reflect an alteration in dopaminergic transmission in patients with pill-related hypertension.

Adult↗

[TRH stimulation as an attempt at demonstration of the induction and involution of prolactin-secreting pituitary cells in pregnancy and puerperium and in pathological hyperprolactinemia].

The present paper discusses the relationship between functional hypertrophia or hyperplasia of the prolactin secreting cells in the pituitary and actual pituitary prolactin reserves in pregnant and post partum women. 35 randomly selected post partum patients from the 3rd to 12th day p.p. and 14 women in their 11th to 14th weeks of pregnancy volunteered to undergo a standard TRH-test. The control group consisted of 60 normoprolactinemic patients. Eleven pathologically hyperprolactinemic patients were compared to the normoprolactinemic and physiologically hyperprolactinemic groups. In all cases, plasma prolactin showed a linear decrease from the 3rd to 12th days post partum. The TRH induced increase became correspondingly greater as the basal prolactin levels decreased, i.e. an inverse relationship between these two parameters was seen. The TRH-induced increase was also always greater than the increase caused by suckling. A connection between prolactin and parity was not found. The inverse relationship between basal prolactin levels and the actual reserves which could be released by TRH stimulation can be explained in that there are two regulatory systems for prolactin. The estrogens stimulate basal prolactin and inhibit prolactin reserves. The actual prolactin reserve is, on the one hand, directly dependent on the degree of endogenous neurohormonal stimulation and, on the other hand, indirectly dependent on the endogenous estrogens through a feedback mechanism. The TRH-stimulation test is not suitable for determining a functional hypertrophia or hyperplasia of lactotropic pituitary cells.

Estrogens↗

Termination of second trimester pregnancy with intraamniotic administration of 16-phenoxy-omega-tetranor-PgE2-methylsulfonamide (SHB 286) alone and combined with oxytocin and calcium gluconate.

Midtrimester abortion was succesfully induced within 30 hours in 62 out of 90 patients by intraamniotic administration of 16-phenoxy-omega-17,18,19, 20-tetranor-prostaglandine-E2-methylsulfonamide. The Pg-analogue was tested in 5 groups of patients which received 1,2 or 3 mg. In group IV, 2 mg of the analogue was combined with oxytocin. In group V, 3 mg of the analogue was combined with 2.75 grams of calcium gluconate. The success rate was significantly influenced by the amount of the drug administered. Side effects were minimal. Multiparous women respond better to the therapy than nulliparous patients. The combination with oxytocin was more effective than the Pg-analogue alone and the combination of sulprostone with calcium gluconate was 87% succesful within 30 hours and 100% succesful within 36 hours.

Abortion, Induced↗

Catechol estrogens and thrombosis: differential effect of 2-hydroxyestradiol and estradiol on prostacyclin release.

High estrogen burden states, such as that seen in women who ingest oral contraceptive preparations, are associated with increased thrombosis. In other instances, however, estrogens decrease thrombogenicity. Variations in conversion to active metabolites could explain this paradox. Thus, we examined the influence of estradiol and a major metabolite, 2-hydroxyestradiol (catechol estrogen), on prostacyclin release from cultured human umbilical venous endothelium. In micromolar concentrations, both compounds inhibited prostacyclin (PGI2) release from bradykinin-, arachidonic acid-, and ionophore-stimulated, as well as unstimulated monolayers. However, when thrombin was used to stimulate release, estradiol enhanced, while 2-hydroxyestradiol inhibited, PGI2 formation. These sex steroids probably exert their influence at micromolar concentrations through a non-specific interaction with the cell membrane, and may be of importance in the predisposition to thrombosis suffered by those who use oral contraceptives.

Cells, Cultured↗

Metabolic effects of progesterone.

Progesterone has important effects on carbohydrate, lipid and protein metabolism. This steroid induces hyperinsulinemia, possibly by direct action on pancreatic islets, while promoting glycogen storage in the liver. Paradoxically, it antagonizes the effects of insulin on glucose metabolism in adipose tissue and skeletal muscle. Progesterone stimulates deposition of body fat but had catabolic effects on protein metabolism. Provisional evidence is offered that the steroid may influence ketone body production by the liver as well. When these steroid actions are considered together, their most relevant expression appears to be the physiologic changes observed during normal pregnancy.

Adipose Tissue↗

Effects of oral contraceptives containing different progestogens on sodium-lithium countertransport in normal females.

In view of the lack of unanimity on the effect of long-term intake of combined oral contraceptives (OC) on external sodium-dependent lithium efflux, otherwise known as sodium-lithium countertransport (SLC), we undertook a double-blind study to investigate the possible interaction between SLC and OC in healthy women with regular menstrual cycles. In a group of 17 volunteers, aged 27.0 +/- 1.1 years (mean +/- s.e.m.) and weighing 61.4 +/- 2.0 kg, ingestion of 30 microg ethinyloestradiol + 150 microg desogestrel for 3 months caused an increase in SLC activity from a baseline value of 0.254 +/- 0.017 mmol/lcell x h to 0.274 +/- 0.017 mmol/lcell x h (P = 0.05). The activity of the transport system after 6 months treatment remained higher than at baseline (0.280 +/- 0.016 mmol/lcell x h, P < 0.025) but was comparable to that at 3 months. Blood pressure and weight remained unaltered during the study period. In a comparable group of 16 volunteers of age 26.1 +/- 1.3 years and weight 63.5 +/- 2.1 kg, control SLC activity (0.218 +/- 0.012 mmol/lcell x h) was comparable to that after 3 months (0.215 +/- 0.011 mmol/lcell x h) and 6 months (0.216 +/- 0.011 mmol/lcell x h) intake of 35 microg ethinyloestradiol + 2 mg cyproterone acetate. Body weight and blood pressure remained similarly unchanged. These results not only confirm that long-term intake of OC may cause increased SLC activity, but also suggest that the type of the progesterone in the medication used could be an important determinant of such interaction.

Adolescent↗

Immunoreactive somatomedin B (RIA-B) in the circulation of healthy adults and patients with endocrine disorders.

The serum and cerebrospinal fluid (CSF) levels of immunoreactive somatomedin B (RIA-B) were examined throughout life in healthy adult humans. A significant decline in serum RIA-B was observed in subjects over 60 years of age. No significant diurnal, daily, or monthly serum variation was observed in healthy subjects aged 20-60 years. However, women taking oral contraceptives had elevated RIA-B values. No significant decline in CSF RIA-B was observed in subjects over 60 years of age. A significantly lower level of RIA-B in CSF was observed in subjects sampled at 20.00 h compared to subjects sampled in the morning. A significant decline in serum RIA-B was observed in patients with hypopituitarism and diabetes mellitus and a significant elevation of serum RIA-B levels was observed in patients with hyperthyroidism. CSF RIA-B was significantly elevated in patients with Cushing's syndrome.

Adult↗

Enhancement of thrombocyte aggregation and thromboxane B2 synthesis by diethylstilbestrol.

Effect of diethylstilbestrol administration on thrombocyte aggregation and thromboxane B2 synthesis was investigated in atherosclerosis-susceptible pigeons. Platelet aggregatory response to arachidonic acid and synthesis of thromboxane B2 from 14C-arachidonic acid was enhanced in thrombocytes derived from diethylstilbestrol-treated pigeons. Platelet total phospholipid concentration was increased in pigeons with diethylstilbestrol treatment. Enhanced thromboxane synthesis might be responsible for increased platelet aggregation, which in turn might contribute to the severe atherosclerosis noted following diethylstilbestrol treatment in several avian species.

Animals↗

Estrogen receptor cleavage and plasminogen activation by enzymes in human breast tumor cytosol.

Estrogen receptors in cytoplasmic extracts of breast tumors from more than 40 patients were separately analyzed by gel filtration and/or ultracentrifugation under diverse conditions. Resultant patterns are presented for specimens from 11 women with infiltrating duct carcinoma and are representative of results obtained in all samples of sufficient size and receptor content (approximately 40 fmol/mg cytosol protein) for accurate determination of hydrodynamic parameters. Estradiol-binding components of intracellular origin were distinguished from the serum contaminant, sex hormone-binding globulin by their high affinity for diethylstilbestrol and negligible affinity for 5 alpha-dihydrotestosterone. The predominant molecular forms of the receptors, but not the steroid specificity, varied dramatically with experimental factors, including the duration of the fractionation procedure, ionic strength, and the presence of protease inhibitors, particularly the bacterial tripeptides N-acetyl- and N-propionyl-L-leucyl-L-leucyl-DL-arginine aldehydes (leupeptin). At least three discrete forms of the intracellular receptors were detected. The smallest labeled complex, the mero-receptor, with a sedimentation coefficient of about 3S and a Stokes radius of about 24 A, was formed during prolonged analysis of control cytosol in hypotonic or hypertonic buffers. Complexes with an intermediate sedimentation coefficient (approximately 5S) and Stokes radius (approximately 34A) were detected when control cytosol was analyzed rapidly in hypotonic buffer or when cytosol containing 50 nM leupeptin was analyzed in hypertonic buffer. The largest receptor form (10.5S, 71A) was predominant in cytosol prepared with 50 mM leupeptin and analyzed in hypotonic buffer. In this small series of patients, there was no obvious correlation between the molecular form of the receptors and the clinical status or eventual responsiveness to endocrine therapy. Preliminary studies of endogenous proteolytic enzymes in breast tumor cytosol that may be involved in mero-receptor formation included assays of plasminogen activators (EC 3.4.21.-) by fibrinolytic and spectrofluorometric techniques. The detection of high concentrations of plasminogen activators in several tumor cytosols and the inhibition of this activity by leupeptin, which stabilizes the large receptor forms in this and other systems, are consistent with a possible role of these enzymes in receptor cleavage.

Aged↗

Induction of the "pregnancy zone" protein by conjugated oestrogens.

Treatment with conjugated oestrogens was found to increase significantly the serum concentration of the pregnancy zone protein (PZ) in a group of postmenopausal women. The basic level of PZ before treatment was comparatively high in this group of women and might be related to age and previous pregnancies. Naturally occurring conjugated oestrogens have a similar effect on the induction of PZ as synthetic oestrogens.

Estrogens, Conjugated (USP)↗