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Biomedical subjects

K J Ryan

Publications and source records attributed to K J Ryan.

At least 199 records · Page 11Linked to original sources
PubMed1975

The effects of dexamethasone on the peripheral plasma concentrations of androstenedione, testosterone and cortisol in the pregnant rhesus monkey.

The concentrations of androstenedione, testosterone and cortisol have been measured in the maternal peripheral plasma of normal pregnant rhesus monkeys (Macaca mulatta), and in rhesus monkeys treated daily with dexamethasone during late pregnancy. During the last 30 days of pregnancy, the mean plasma concentrations of androstenedione, testosterone and cortisol were about 1400-2000 pg/m1375-425pg/ml and 300-400 ng/ml, respectively. None of these steroids increased significantly before parturition. As there was no rise in maternal androgens in late pregnancy when plasma estrogens increase sharply, it suggested that his elevation of plasma estrogens is related to an increase of fetal precursors Dexamethasone treatment resulted in 90% suppression of plasma cortisol and 40%-60% suppression of androstendione and testosterone. As the suppression of maternal androgens was of lesser magnitude than the decline of plasma estrogens, and as the androgens did not continue to fall with continuing dexamethasone treatment as did the estrogens, these findings also suggest that the decline in plasma estrogens is related in large part to suppression and atrophy of the fetal adrenals.

Androstenedione↗
PubMed1975

Progesterone, androstenedione, testosterone, estrone, and estradiol synthesis in hamster ovarian follicle cells.

Isolated granulosa cells and theca from proestrous hamsters alone and in recombination, were cultured in order to study steroidogenic capacity of this tissue. Cells from medium size antral follicles (100-300 mum diam.) and large preovulatory follicles (500 plus mum diam.) were used. Steroids were measured by radioimmunoassay. Cultures of cells derived from both sizes of follicles made significant amounts of progesterone for up to 6 days in tissue culture. The preparations from the medium sized antral follicles synthesized little or no estrogen. Of the cells harvested from the preovulatory follicles, the granulosa and theca made moderate amounts of estradiol-17beta while the recombined system made similar to 5 times the estradiol-17beta made by theca or granulosa alone. The results indicate that in the in vitro system used: 1) The hamster follicle cells are similar to other species in that they spontaneously luteinize in culture and secrete large amounts of progesterone, 2) Androgen accumulation is greatest in media from cultured theca of preovulatory follicle, 3) A synergism between theca and granulosa of the large preovulatory follicle exists to effect maximal estrogen synthesis, and 4) Estrogen synthesis is short-lived in vitro in contrast to continued progesterone production.

Androstenedione↗
PubMed1975

The effect of LH/FSH, dibutyryl cyclic AMP, and prostaglandins on the production of estrogens by rabbit granulosa cells in vitro.

The purpose of this study was to establish the effects of trophic hormones on the production of estrogens by rabbit granulosa cells. A pure population of these cells was isolated from preovulatory follicles (1-15 mm in diameter) of estrous rabbits, and cultured for 6 days with either one or a combination of the following hormones: androstenedione, Pergonal (LH/FSH), dibutyryl cyclic AMP (Bu2cAMP), prostaglandin F2alpha (PGF2alpha), or prostaglandin E2 (PGE2). The medium was collected every 2 days and progesterone (P), estrone (E1) and estradiol-17 beta (E2beta) were measured by radioimmunoassay. Granulosa cells cultured as controls (i.e., without exogenous trophic hormones) secreted P spontaneously and its secretion was stimulated 100 to 1,000 fold with LH/FSH and Bu2cAMP, but not with PGF2alpha or PGE2. Androstenedione, either alone or with trophic hormones had no apparent effect on the cytology of the granulosa cells or their ability to secrete P. In the absence of exogenous androstenedione, the cultures produced very small amounts of E1 or E2beta (smaller than 100 pg/ml), either spontaneously or in response to LH/FSH, B12cAMP, PGF2alpha, or PGE2. Incubating granulosa cells with exogenous androstenedione (1 mug/ml) resulted in a 30- to 150-fold increase in E2beta production, which was stimulated an additional 3- to 5-fold with LH/FSH and Bu2cAMP, but not with PGF2alpha or PGE2. In most cultures, E2beta production was restricted to the first 2 days in vitro. Bu2cAMP, however, maintained E2beta production at relatively high levels throughout the duration of the experiment, but there was a progressive decrease in its production. The production of E1 was only 5 percent of E2beta, but the pattern of secretion was similar for both estrogens. These results suggest that cyclic AMP could have a role in regulating the synthesis of estrogens by rabbit granulosa cells.

Androstenedione↗
PubMed1975

The affinity of catechol estrogens for estrogen receptors in the pituitary and anterior hypothalamus of the rat.

The purpose of these experiments was to evaluate the potential for interaction between 2-hydroxyestrone and 2-hydroxyestradiol and estrogen receptors in rat pituitary and anterior hypothalamus. The 150,000 X g supernatant fractions of these tissues were prepared, the estrogen receptor-site concentration was measured, and the relative abilities of unlabelled estradiol, estrone, 2-hydroxyestradiol and 2-hydroxyestrone to compete with [3H]estradiol for estrogen binding sites was determined. From these results, and the previously determined association constant for [3H]estradiol, 10(10)M-1, the association constants of the other estrogens were calculated. The introduction of the 2-hydroxy group caused only a modest reduction in the affinity of these estrogens for the receptors. The association constants of the 2-hydroxy derivatives were within one order of magnitude of those of the parent compounds. These results demonstrate the potential for interaction between catechol estrogens and estrogen receptor in rat brain and pituitary of a magnitude which could be biologically significant.

Animals↗
PubMed1975

Aromatization of androgens by human abdominal and breast fat tissue.

The ability of human abdominal, breast and axillary fat to convert androgens into estrogens was investigated by incubating labeled substrates in the presence of NADPH with a variety of cell preparations. The incubation products were subjected to phenolic partition, paper chromatography, methyl-ether formation, repeat chromatography and crystallization with cold carrier reference standards to constant specific activity. Androstenedione was converted to estrone and, to a lesser extent, to 17beta-estradiol by crude homogenates, minces, fat-free particulate fractions (1,000-100,000 time g) and isolated fat cells obtained from abdominal, breast or axillary fat. Testosterone was found to be aromatized as actively as androstenedione, but inthis case more 17 beta-estrodiol was formed than estrone. 19-Hydroxyandrostenedione-2 also served as substrate, givingresults similar to those obtained with androstenedione. Fat tissue obtained from cancerous breasts was found to be as active as normal breast fat (1-4 pg/g fat/90 min) and within the range found for abdominal fat (1-27 pg/g fat/90 min). In each case in which axillary fat was compared to breast fat from the same subject, the activity of the axillary fat was 5 to 10 times higher. The results indicate a possible role of adipose tissue as a significant extra-gonadal source of estrogens.

Abdomen↗
PubMed1975

Plasma estetrol as an index of fetal well-being.

Estetrol (15alpha-hydroxyestriol or E4) is considered to be a specific product of fetal liver and has been suggested as a good indicator of fetal well-being. The concentration of unconjugated estetrol (E4) was measured by rapid and specific radioimmunoassay in 1 ml of maternal plasma. E4 levels prior to the 18th week of pregnancy were often undetectable (smaller than 50 pg/ml). The mean plasma E4 level at term of 1.2 ng/ml was 7-fold higher than that observed at 24 weeks of gestation, and no diurnal variations were found. E4 levels in fetal plasma at term were 12-fold higher than those in maternal plasma and no fetal arterial venous differences were found. Umbilical vein but not maternal plasma levels of patients undergoing vaginal delivery were higher than those undergoing cesarean section (P smaller than 0.05) suggesting increased adrenal output of E4 precursors during labor. In patients with severe Rh-isoimmune disease plasma E4 levels were not helpful in assessing fetal well-being. However, in patients with chronic hypertension or pre-eclampsia, subnormal plasma E4 concentrations always preceded intrauterine fetal death. Plasma E4 appears to be a good indicator of fetal well-being in patients with hypertensive disease of pregnancy.

Amniotic Fluid↗
PubMed1975

A specific, high-affinity, limited-capacity estrogen binding component in the cytosol of human fetal pituitary and brain tissues.

A macromoleclar component which binds 3H-estradiol with high affinity and limited capacity is present in the 150,000 x g supernatant fraction of pituitary, hypothalamus, cortex, and limbic system of both male and female human fetwses. 17 beta-estradiol and 17alpha-ethinylestradiol effectively compete with 3H-estradiol for binding sites while testosterone, dihydrotes-tosterone, and cortisol do not. The binding component is different from sexhormone-binding-globulin. It is present in these tissues in relatively large amounts and it is tentatively identified as an estrogen recptor.

Binding Sites↗
PubMed1975

The effects of dexamethasone and indomethacin on the outcome of pregnancy in the rabbit.

Pregnant rabbits were treated with indomethacin (8-10 mg/kh/day) or dexamethasone (1-2-1-8 mg/kh/day) during late gestation. The effects of these treatments on the concentrations of progesterone and prostaglandin F (PGF) in the peripheral plasma, and the outcome of gestation was studied. Treatment with indomethacin significantly prolonged the length of gestation (P smaller than 0-01) compared iwth control, untreated animals. In these treated animals, the plasma progesterone levels declined at a similar time to that in control rabbits but the increase in systemic PGF normally seen during late pregnancy was reduced. Dexamethasone treatemnt reliably induced premature delivery within 3-6 days. The plasma progesterone concentration fell rapidly during the first 24 h of dexamethasone administration, but in no animal was this associated with a significant increase in the plasma levels of PGF. These results are consistent with the suggestion that prostaglandins are involved in the normal initiation of parturition in the rabbit. They do not support the hypothesis that the effect of dexamethasone on the length of gestation is mediated through an increase in the production of prostaglandin F.

Administration, Oral↗