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Biomedical subjects

R Lester

Publications and source records attributed to R Lester.

At least 55 records · Page 3Linked to original sources
PubMed1985

Excretion of cholate glucuronide.

[3-3H]Cholic acid glucuronide [7 alpha,12 alpha-dihydroxy-3 alpha-O-(beta-D-glucopyranosyluronate)-5 beta- cholan-24-oate] was synthesized and administered to rats prepared with either an external biliary fistula or a ligated bile duct. When bile fistula animals were given either microgram or milligram amounts of the glucuronide, biliary secretion of label was rapid and efficient: greater than 90% of the administered label was secreted within 60 min and total recovery of label in bile was 98.6 +/- 1.2%. Studies in which [14C]taurocholate was included in the dose indicated that this bile acid was secreted into bile significantly more rapidly than was the glucuronide. In animals with ligated bile ducts, urinary excretion was the major route of elimination: after 20 hr, 83.4 +/- 9.3% of the administered dose had been excreted in urine. Urinary excretion of cholate glucuronide was significantly more rapid than that of taurocholate. Gas-liquid chromatographic analysis of the methyl ester acetate derivatives of labeled compounds isolated from bile and urine by chromatography established that the bulk (greater than 70%) of the administered material was secreted in bile or excreted in urine as the intact cholate glucuronide. From these results, we conclude that the glucuronidation of cholic acid produces a derivative which is rapidly and effectively cleared from the circulation and excreted.

Animals↗
PubMed1979

Intestinal absorption of bile salts: immature development in the neonate.

The intestinal absorption of sodium taurocholate was studied in fetuses, neonates, infants, children, and adults. Absorption rates were measured in vitro in everted rings of jejunum and ileum. Mucosal accumulation of 3H-taurocholate against a concentration gradient was consistently demonstrated in rings of ileum from adults, children, and infants older than 8 months, whereas fetal and neonatal ileal mucosal concentrations were not significantly above those in the incubation medium after exposure of the mucosa to 0.003, 0.03, and 0.3 mM taurocholate. There were no significant differences in mucosal uptake of taurocholate by perinatal jejunal and ileal rings. Incubations of mucosa from older infants, children, and adults in 0.3 mM taurocholate exhibited saturation phenomena. It is concluded that the ileal mechanism for active transport of taurocholate is undeveloped in the fetus and newborn infant. It is probable that the enterohepatic circulation of bile salt during the perinatal period is limited to that fraction of bile salt absorbed passively. The results suggest that losses of bile salt from the immature intestine may contribute to the steatorrhea and so-called diarrhea of newborn infants.

Aged↗
PubMed1979

Synthesis of taurocholate by rat fetal liver in organ culture: effects of cortisol in vitro.

Taurocholate production by fetal hepatic organ cultures was measured by radioimmunoassay. Taurocholate production was maximal on day 1 of in vitro incubation, but was demonstrable in organ cultures maintained for periods up to 15 days. Explants obtained from fetuses of 18 gestational days of age produced only 82 pmol taurocholate per milligram dry weight of tissue during the first 24 h of incubation. Explants obtained from fetuses 21 gestational days of age produced 1,043 pmol taurocholate per milligram dry weight. The presence of cortisol (2.0 X 10(-6) M) in the incubation medium increased synthesis of taurocholate by rat fetal liver in which total taurocholate rose 50-fold above control after 120 h of incubation. In increasing concentrations from 2.0 X 10(-9) M to 2.0 X 10(-7) M, cortisol produced an incremental rise in taurocholate. However, additional increases in cortisol dose failed to provide further stimulation, and taurocholate production was inhibited by cortisol concentrations of 2.0 X 10(-5) M. The results provide further validation for the technique of fetal hepatic organ culture. They demonstrate that taurocholate synthesis is increasing rapidly during the final stages of gestation and show that cortisol augments taurocholate synthesis in a dose-response pattern.

Animals↗
PubMed1979

Taurocholate pool size and distribution in the fetal rat.

Taurocholate concentrations in fetal and neonatal rats were determined by radioimmunoassay. Total body taurocholate pool size varied from 0.0049 +/- 0.0008 to 203 +/- 8 nmol/g body weight from day 5 of gestation to 5 d after birth. A 50-fold increase in taurocholate pool size was observed between days 15 and 19 of gestation. The distribution of taurocholate between liver, intestine, and the remainder of the carcass was determined for rats of gestational age 19 d to 5 d after birth. The major fraction of total body taurocholate was in the liver and intestine, with less than 15% in the remainder of the carcass. The ratio of taurocholate in intestine to taurocholate in liver, which was 1:17 at 19 d of gestation, had altered substantially to a ratio of 6:1 by 5 d after birth. Treatment of pregnant rats with 60 microgram/d of dexamethasone from gestational day 9 until sacrifice increased fetal taurocholate pool size by 80% at 15 d, 40% at 19 d, and 16% at 1 d after birth. Administration of dexamethasone to the mother also changed the ratio of taurocholate in intestine to taurocholate in liver. At 19 d of gestation, dexamethasone-treated mothers had fetuses with approximately equal amounts of taurocholate in intestine and liver. This suggested that adrenocorticosteroids stimulate the early maturation of factors controlling taurocholate pool size and tissue distribution in the rat fetus.

Animals↗
PubMed1979

Mechanisms of hypogonadism and feminization in alcholic liver disease.

Based upon studies in man and animals it is proposed that: 1. Alcohol-induced hypogonadism is primarily due to a direct testicular toxicity of ethanol manifested by alcohol-induced reduced testosterone levels. 2. In addition, an alcohol-induced central defect also may contribute to the observed hypogonadism. 3. In contrast to the ease with which hypogonadism can be ascribed to androgen deficiency per se, the observed feminization can not be ascribed to altered estrogen levels alone. Rather, we would propose, that feminization of such men is due to the combined effects of estrogen excess and androgen deficiency upon the patter of estrogen-binding proteins in hepatic cytosol.

Animals↗
PubMed1978

Evidence for autonomous secretion of prolactin in some alcoholic men with cirrhosis and gynecomastia.

Prolactin responses to provocative thyrotropin releasing hormone (TRH) stimulation were evaluated in 20 cirrhotic men with gynecomastia. Fifteen of these cirrhotic men had normal responses with a minimum doubling of the prolactin concentration above basal in response to TRH. Five had abnormal (autonomous) responses in that they failed to double their basal level or had a paradoxical decrease from basal in response to TRH. Moreover, these same five men failed to have a sleep-related increase in plasma prolactin. Three of them also failed to respond to chlorpromazine stimulation. Such abnormal responses are generally associated with the presence of a prolactin secreting pituitary tumor. Basal plasma levels of prolactin were measured in all 20 men studied. The five men who failed to respond to TRH had significantly greater basal prolactin concentrations (80.5 +/- 18.7 ng/ml) than did the 15 men who responded normally (33.7 +/- 4.3 ng/ml) (p less than 0.01), although all 20 had increased prolactin levels relative to that of controls (10.8 +/- 0.9 ng/ml) (both p less than 0.01).

Gynecomastia↗
PubMed1978

Further evidence for hypothalamic-pituitary dysfunction in alcoholic men.

Reduced plasma levels of testosterone and a high frequency of azoospermia have frequently been reported in alcoholic men. Despite the high grade of gonadal failure present, plasma gonadotropins have ranged from normal to only moderately increased. This has been interpreted as suggesting that a central hypothalamic-pituitary defect also might exist in these men. Clomiphene stimulation studies have been consistent with the hypothesis of a central defect. The present work consists of studies utilizing luteinizing hormone-releasing factor and thyrotropin-releasing factor in an effort to examine the hypothesis of whether this central defect exists and, if so, whether at an anatomic, hypothalamic, or pituitary level.

Adolescent↗
PubMed1978

Alcohol-induced ovarian failure in the rat.

The effect of ethanol feeding on ovarian function and structure in female rats was studied in alcohol-fed animals, isocalorically fed controls, and two ad libitum-fed control groups. Ovarian weight was reduced by 60% in alcohol-fed animals compared with the control groups. Gross disruption of ovarian architecture was noted, characterized by the absence of any corpus hemorrhagicum and corpus albicans. Moreover, plasma levels of estradiol were significantly reduced in the alcohol-fed animals (P < 0.01) compared with the levels found in isocaloric controls. Plasma levels of estrone and corticosterone were increased in alcoholfed and isocaloric control animals relative to those of ad libitum-fed animals suggesting a primarily adrenal, rather than ovarian, origin for these two steroids. Despite the increase in estrone, the secondary sex organs (uterus and fallopian tubes) reflected marked estrogen deprivation presumably as a result of estradiol insufficiency. Progesterone levels in the alcohol-fed animals were significantly less than levels in the isocaloric and intact ad libitum-fed controls but were not significantly different compared to oophorectomized animals. Plasma follicle-stimulating hormone levels were similar in alcohol-fed, isocaloric controls, and ad libitum-intact controls. They were, however, one-third the level of oophorectomized controls. Both alcohol-fed and isocaloric controls had increased levels of plasma luteinizing hormone, although levels were below those seen in oophorectomized controls (P < 0.01). The results establish that ingestion of a diet containing 5% ethanol for periods as short as 6 wk produces functional and histologic ovarian failure in the female rat.

Animals↗
PubMed1978

Evidence for a defect in pituitary secretion of luteinizing hormone in chronic alcoholic men.

To characterize the defect in the hypothalamic-pituitary-gonadal axis of alcoholic men, acute and chronic LRF responses were evaluated in 22 chronic alcoholic men with varying degrees of biochemically and histologically confirmed liver disease. In addition, acute LRF responses in 14 normal men, before and at the end of 72 h of administration of 2 ml/kg/day 95% ethanol, were evaluated. The alcoholics hd significantly reduced basal testosterone and elevated gonadotropin levels (both FSH and LH) compared to the normal volunteers (P less than 0.02). Serum concentrations of estradiol and PRL did not differ between alcoholics and normal volunteers. A 100-micrograms bolus of LRF resulted in a 3-fold increase of LH in alcoholic men as compared to a 6-fold increase of serum LH in normal volunteers. No significant difference in the LRF-induced FSH responses was observed. When the response of normal volunteers to LRF before and after ethanol administration was evaluated, basal levels of both gonadotropins were increased after alcohol administration and a reduced LRF-induced LH response was observed. Based upon these results, we conclude that: 1) the central hypothalamic-pituitary defect known to exist for LH secretion is in part due to inadequate pituitary secretion and 2) acute alcohol ingestion in normal men suppresses the LRF-induced LH but not the FSH response.

Adult↗
PubMed1977

Gonadal function in chronic alcoholic men.

Alcoholism affects nine million individuals in the United States according to United States Government estimates. As many as 80% of hard-core alcoholic men show evidences of feminization including impotence, testicular atrophy, sterility, gynecomastia and changes in bodily hair. The causes of feminization of male alcoholics have remained obscure until recently. Largely as a result of advances in the techniques of measurement of sex hormones, it has become possible to begin to examine the pathogenesis of feminization. The results of initial studies suggest that alcoholics become feminized through the secondary effects of alcohol-induced liver disease, and also through primary effects of alcohol on the endocrine system. It can be shown that liver disease permits the peripheral escape of steroid precursors and their conversion to estrogenic substances. These substances are then inadequately cleared by the liver. In addition, however, alcohol alters testicular steroidogenesis and testosteronogenesis. Hypothalamic-pituitary function also is diminished in chronic alcoholics, and this change contributes to the syndrome of feminization.

Alcoholism↗