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At least 19 recordsLinked to original sources

Central control of hepatic steroid metabolism: effect of discrete hypothalamic lesions.

The effects of various hypothalamic lesions on hepatic steroid metabolism in adult rats were investigated. It was found that frontal deafferentation at the retrochiasmatic and suprachiasmatic level resulted in a complete "feminization" of hepatic steroid metabolism in male rats. Such an effect was also seen when lesions involving mainly the anterior periventricular hypothalamic area and the suprachiasmatic nucleus were performed in male rats. Midline lesions, anterior to the suprachiasmatic nucleus, on the other hand, did not result in any significant effects. A moderate degree of "feminization" was obtained after bilateral lesions involving mainly the nucleus interstitialis striae terminalis but including also parts of the anterior commissure. Small lesions in the lateral preoptic area were, however, without effect. No effects were seen of analogous lesions in female rats in any of the cases studied. The present findings suggest that a region including the anterior hypothalamic periventricular area, the suprachiasmatic nucleus and adjacent areas is involved in the control of hepatic steroid metabolism. It is postulated that the neuronal cell bodies that produce a factor with an inhibitory effect on the secretion of "feminizing factor" have their origins in this area of the hypothalamus, or, alternatively, may send axons through this area to the basal hypothalamus and thus directly or indirectly influence the anterior pituitary gland.

Afferent Pathways

[Effect of diuresis on the results of quantitative estrogen- and HCG determinations].

Investigations on the influence of the diuresis effect upon the results of quantitative oestrogen and HCG determinations revealed that the oestrogen values increase with the 24-hour amount of urine. Oliguria and polyuria affect oestrogen excretion to a considerable extent; they have to be taken into account in prenatal diagnosis of pregnancy. Comparative HCG checks show that HCG concentration also varies considerable depending on fluid excretion. Diagnostic errors can be diminished or avoided when the quantitative HCG assessment is made on the 24-hour urine and then referred to the whole amount of urine.

Chorionic Gonadotropin

Steroid absorption and enterohepatic recycling.

A short review on steroid absorption and enterohepatic recycling in man with special emphasis on contraceptive and related steroids is presented. Some new experimental data on the intestinal metabolism of steroids is described and includes further observations on the effect of antimicrobial agents on steroid hormone metabolism. Evidence is presented that plasma levels of steroids may be influenced if the intestinal microflora is altered. Some formation of biologically active steroids, like estradiol, may occur in the intestinal tract and this may have both biological and pathological consequences and may be influenced by such factors as diet and sex. It is concluded that our knowledge of the intestinal and especially, the mucosal metabolism of steroids is scanty and further studies are needed to clarify the role of the intestine and enterohepatic circulation in determining the bioavailability of natural and synthetic steroids.

Absorption

Mechanism of action of glucocorticoids in induction of ovine parturition: effect on placental steroid metabolism.

Maternal plasma progesterone levels in sheep may fall dramatically druing the last few days of gestation and following the administration of glucocorticoids to the foetus. To investigate the mechanism of the fall, metabolism of [3H] progesterone in vitro by ovin placental tissue was studied in five ewes before and after intra-foetal administration of dexamethasone in a dosage sufficient to induce parturition, and in one ewe after the spontaneous onset of labour at 143 days of gestation. Manual separation of maternal and foetal placental tissues showed that, in 11 out of 12 cases, the foetal and not the maternal placenta produced progesterone from pregnenolone in vitro. Total activities of cholesterol side-chain cleavage enzyme and 3beta-hydroxysteroid dehydrogenase in the foetal placenta were not influenced by intra-foetal dexamethasone. Befre administration of dexamethasone, homogenates of foetal placenta converted [3H] progesterone to 20alpha-hydroxy [3H]pregn-4-en-3-one in the presence of NADPH. Within 12 h of administration of dexamethasone, and after the natural onset of labour at 143 days, large amounts of 17alpha, 20alpha-dihydroxyI1pregn-4-en-3-one were formed form [3H]progesterone. Intra-foetal dexamethasone treatment also induced the formation of 17alpha, 20alpha-dihydroxy[3H]pregn-4-en-3-one by miced foetal placental tissue incubated with [3H]pregnenolone. This change in steroid metabolism did not occur in foetal placental tissue from a sham-operated animal receiving no dexamethasone. Assay of progesterone in foetal placentae showed that the increased fromation of 17alpha,20alpha-dihydroxypregn-4-en-3-one was unlikely to be caused by a change in the specific activity of added 3H-labelled precursor, although the production of 17alpha, 20alpha-dihydroxypregn-4-en-3-one in vitro increased at a time when both foetal placental and utero-ovarian venous levels of progesterone were decreasing in response to dexamethasone treatment. These observations indicate that intra-foetal dexamethasone treatment induces a placental 17alpha-hydroxylase enzyme, which is also present in foetal placental tissue after the spontaneous onset of labour at term.

17-alpha-Hydroxypregnenolone

Metabolic effects of anabolic steroid on skeletal muscle.

The purposes of this investigation were to examine the effects of anabolic steroid treatment on protein synthesis in skeletal muscle and on steroid receptors. The experiments were conducted with 230 male albino rats maintained on a diet containing 20% protein. Anabolic steroids (methandrostenolone, methylandrostendiole, and Retabolil) were injected in doses of 0.5 mg/kg body weight. The animals were examined at rest and after swimming exercise of 15 min duration. Quadriceps and gastrocnemius muscle were used for analysis in all experiments. Protein synthesis was studied by means of 14C-leucine incorporation. It was found that anabolic steroid treatment resulted in an increased content of skeletal muscle protein: myosin, myofibrillar, and sarcoplasmic fractions. The activity of RNA-polymerase in skeletal muscle nuclei was increased. The results indicated that in skeletal muscle there were androgen receptors which were binding sites for 3H-testosterone and anabolic steroids. A model for the anabolic steroid action on the regulation of protein synthesis in skeletal muscle was proposed.

Anabolic Agents

Human urinary and liver conjugates of 17alpha-ethnylestradiol.

Chromatographic profiles of the conjugates of 17alpha-ethynylestradiol (EE2) were obtained from the urine of castrate and normal women given tritium labeled EE2 orally. Five distinct radioactive peaks were observed, with considerable quantitative variation between individuals. Glucosiduronate fractions comprised the dominant excreted radioactivity. In vitro incubation of normal human liver also produced five conjugate types. Simultaneous intravenous/oral (14C/3H) administration of EE2 demonstrated conversion to identical urinary conjugate and free steroid products, with a greater excretion of the intravenous material. Authentic 3-glucuronide of EE2 was synthesized and its position in the chromatographic system relative to the urinary conjugate peaks demonstrated.

Adult

The urinary metabolites of 17alpha-ethynylestradiol-9alpha,11xi-3H in women. Chromatographic profiling and indentification of ethynyl and non-ethynyl compounds.

Metabolites of 17alpha-ethynylestradiol (EE2) were obtained from human urine following ingestion of tritium-labeled EE2. Over 95% of the recovered activity was found as conjugated steroids and these were separated into four groups by chromatography of the urine extract on Sephadex LH-20 with chloroform-methanol (1/1) + 0.01M NaCl. The two major conjugate fractions appeared to be almost exclusively glucosiduronates. Enzymatic hydrolysis liberated at least ten different EE2 metabolites as shown by chromatography on Sephadex LH-20 with benzene-methanol (85/15). After additional separation and purification of these metabolites, positive identification was obtained for nine radioactive compounds by either gas liquid chromatography-mass spectrometry or reverse-isotope recrystallization. Five were ethynyl compounds: EE2, 2-MeO EE2, 16beta-OH EE2, 2-OH EE2 and 6alpha-OH EE2. The other four were de-ethynylated estrogens: estrone, estradiol-17beta, estriol, and 2-Me-O-estradiol-17beta.

Chromatography, Gas

Enzyme induction by oral testosterone.

Six normal male volunteers ingested a dose of 400 mg free testosterone daily as tablets over 21 days. By the end of treatment intravenous antipyrine half-life had decreased significantly from 8.0 +/- 2.7 to 5.7 +/- 2.6 hr. The subjects eliminated testosterone from serum more rapidly on the twenty-first day of testosterone ingestion than on the first day. Serum albumin, bilirubin, prothrombin, alanine-amino-transferase, and alkaline phosphatases were unchanged during the experiment. It is concluded that oral testosterone treatment induces the hepatic drug-metabolizing system including that of testosterone.

Administration, Oral