PubMed Health⌕ Search

Biomedical subjects

L Markiewicz

Publications and source records attributed to L Markiewicz.

At least 37 records · Page 2Linked to original sources
PubMed1988

C19 adrenal steroids enhance prostaglandin F2 alpha output by human endometrium in vitro.

Dehydroepiandrosterone sulfate significantly increased prostaglandin F2 alpha output by fragments of human secretory endometrium during the first and second 24-hour periods of incubation in Ham's F-10 medium containing 10% charcoal-treated calf bovine serum. The effects of dehydroepiandrosterone sulfate were noted at 10(-6) mol/L concentrations, which are close to the normal plasma levels of this compound. For the purpose of comparison, the effects of estradiol at 10(-8) mol/L and those of unconjugated dehydroepiandrosterone, dehydroepiandrosterone acetate, 5-androstene-3 beta, 17 beta-diol, or 5 alpha-dihydrotestosterone were evaluated at 10(-8) to 10(-8) mol/L concentrations in parallel experiments. All of the delta 5-C19 steroids tested enhanced prostaglandin F2 alpha output at 10(-6) mol/L but not at 10(-8) mol/L; 5 alpha-dihydrotestosterone was inactive at 10(-6) mol/L but showed a stimulatory effect at 10(-5) mol/L in two experiments. The stimulation of prostaglandin F2 alpha production by the adrenal steroids was significantly reduced by the antiestrogen 4-hydroxytamoxifen at 10(-6) mol/L (a finding consistent with the reported utilization of the estrogen receptor for their actions on other systems) but was not affected by the antiandrogen 4-hydroxyflutamide at 10(-6) mol/L. Progesterone (10(-7) mol/L) also lowered the effects of dehydroepiandrosterone (10(-6) mol/L) and 5-androstene-3 beta,17 beta-diol (10(-6) mol/L), as well as those of estradiol (10(-8) mol/L). delta 5-C19 steroids at 10(-6) mol/L levels did not antagonize the effect of 10(-8) mol/L estradiol, whereas 5 alpha-dihydrotestosterone reduced it by 50% at these concentrations. The significant effect of 5 alpha-dihydrotestosterone points to potential antiestrogenic effects of the C19 compounds that may be manifested in vivo at particular C19/estradiol concentration ratios. The demonstration of direct estrogenic effects of delta 5-C19 steroids, which are not significantly converted to estrogens in vivo, justifies their use in estrogen replacement preparations and indicates that aromatase inhibitors may not eliminate completely the stimulation of estrogen-responsive breast and endometrial tumors by the patient's adrenal steroids.

Androstanes↗
PubMed1988

In vitro effects of clomiphene citrate on human endometrium.

Since cis-clomiphene citrate (CC) used for ovulation induction may affect embryo implantation during in vitro fertilization, direct effects of the drug on human endometrium were tested. Estrogenic and antiestrogenic effects were evaluated in vitro by measuring changes in prostaglandin (PG) output provoked by estradiol (E2), CC, and mixtures of E2 and CC; progestagenic effects were tested with E2 17 beta-dehydrogenase activity and glycogen accumulation as end points. In secretary endometrium, 10(-6)M CC about doubled the basal output of PGF2 alpha and PGE2; 10(-8)M E2 increased the production of these PGs 3-fold and 1.8-fold, respectively. The effects of E2 at this concentration were not diminished by the addition of CC, even at 100-fold molar excess, under conditions in which 10(-7)M progesterone or 10(-6)M 4-hydroxytamoxifen suppressed completely the action of the natural estrogen. In proliferative endometrium, 10(-8)M and 10(-6)M CC had no consistent effect on E2 17 beta-dehydrogenase activity or glycogen accumulation. These results demonstrate that, under in vitro conditions, CC can exert direct estrogenic effects on the endometrium but does not act as an antiestrogen or a progestagen.

Clomiphene↗
PubMed1987

Estradiol enhances prostaglandin synthase activity in epithelial but not in stromal cells of human endometrium.

Exogenous estradiol (E2) has been shown to elevate PGF2 alpha output by explants of human secretory endometrium and in monolayer cultures of glandular epithelial, but not of stromal cells isolated from endometrium. In this study, PGF2 alpha output was measured in each of these cultures in the presence of E2 and the calcium ionophore A23187, added singly or in combination. The ionophore, known to liberate arachidonic acid (AA) by stimulating phospholipase activity, produced a calcium-dependent increase in PGF2 alpha output in the cultures of epithelial cells, whereas greater than additive effects were obtained with mixtures of E2 and A23187. In contrast, PGF2 alpha levels were not elevated by A23187 in the stromal cell cultures even in medium supplemented with CaCl2 or when E2 was added. A calcium-dependent increase in PGF2 alpha output was also observed in fragments of secretory endometrium incubated with A23187. Effects on PGF2 alpha output by endometrial fragments incubated with E2 and A23187 were essentially additive and intermediate between those of the two component cells types. Arachidonic acid produced similar increases in PGF2 alpha output in the epithelial and stromal cell cultures but only in the epithelial cell cultures was there greater utilization of AA in the presence of E2. When mixtures of E2 and AA were added to the cultures of epithelial cells the increase in PGF2 alpha output was 2.5-fold greater than the sum of the increases elicited by E2 or AA alone. In contrast, no enhancement of the AA effect by E2 was observed in the stromal cell cultures. Extrapolation of these results from cell cultures to intact tissue suggests that the epithelium and not the stroma is the primary target for the effects of E2 on PGF2 alpha output by secretory endometrium. The synergistic actions of E2 and either AA, the obligatory precursor of PGF2 alpha, or A23187, an enhancer of AA release from phospholipid stores, point to a stimulatory effect of E2 on prostaglandin synthase activity.

Arachidonic Acid↗
PubMed1987

Differential effects of estradiol, arachidonic acid, and A23187 on prostaglandin F2 alpha output by epithelial and stromal cells of human endometrium.

Primary monolayer cultures of glandular epithelial cells and stromal cells derived from human endometrial curettings release similar amounts of prostaglandin F2 alpha (PGF2 alpha) to the incubation medium, but PGF2 alpha output is significantly increased by estradiol (E2; 10(-8) M) only in epithelial cells. The differential responsiveness to estrogens of these two cell types was further demonstrated in the presence of exogenous arachidonic acid (AA), a PG precursor that markedly elevated PGF2 alpha output by both epithelial and stromal cells. In epithelial cell cultures, the increases in PGF2 alpha output obtained with mixtures of E2 and AA were about 2.5-fold greater than the sum of the increases elicited by E2 or AA alone. In contrast, the effects of AA in stromal cell cultures were not enhanced by E2. Addition of the calcium ionophore A23187 to cultures of epithelial cells resulted in a Ca2+-dependent increase in PGF2 alpha output, which could be further augmented by E2 to levels almost twice the sum of those produced by each agonist alone. Unlike its effects on epithelial cells, A23187 did not significantly increase PGF2 alpha levels in stromal cell cultures, regardless of the addition of Ca2+ (1.5 mM) or E2 (10(-8)M) to the culture medium. These results suggest that the epithelia and not the stroma are the primary targets for the effects of E2 on PGF2 alpha output by the endometrium. The synergistic effects of E2 and AA (the substrate for PG synthase) or of E2 and A23187 (a stimulator of phospholipase-mediated release of AA from phospholipid stores) on PGF2 alpha production suggest that estrogens enhance PG production in epithelial cells by elevating PG synthase activity.

Arachidonic Acid↗
PubMed1986

Hormonal effects of PGF2 alpha output by cultures of epithelial and stromal cells in human endometrium.

Estradiol stimulation and progesterone inhibition of human uterine PGF2 alpha production were studied using in vitro preparations of endometrial tissue and cells. Measurement of PGF2 alpha levels in media from primary cultures of glandular epithelia and stoma revealed that basal outputs were similar in both cell types but could be increased by estradiol only in epithelial cells. Tamoxifen (Tam) and trans-4-hydroxy tamoxifen (OHTam) did not affect basal PGF2 alpha outputs by secretory endometrium in organ culture and by monolayer cultures of epithelial cells, but counteracted the stimulatory effects of estradiol in both systems. The almost pure antiestrogenic activity exhibited by OHTam was at least 10 times greater than that of Tam, suggesting that the estrogen-stimulated increases in uterine PGF2 alpha output are mediated by specific estrogen receptors. Fragments of endometrium also released lipocortin, a phospholipase A2-inhibiting protein believed to mediate inhibitory effects of glucocorticoids on prostaglandin production in several types of cells. Although dexamethasone increased lipocortin and decreased PGF2 alpha output in secretory endometria in vitro, progesterone inhibited both lipocortin and PGF2 alpha output. The mechanisms by which P inhibits PGF2 alpha production remain to be elucidated.

Annexins↗
PubMed1986

In vitro inhibition with antiestrogens of estradiol effects on prostaglandin F2 alpha production by human endometrium and endometrial epithelial cells.

It has been previously reported that neither an antiestrogen, actinomycin D, nor cycloheximide inhibited estradiol (E2)-stimulated elevations in uterine prostaglandin F2 alpha (PGF2 alpha) production in ovariectomized rats, suggesting that in contrast to other steroid-initiated events, this effect on PGF2 alpha may not involve receptor-mediated transcription-dependent actions of E2. To eliminate indirect influences, the ability of antiestrogens to affect PGF2 alpha output was reevaluated during incubations of human secretory endometrium and in cultures of epithelial cells derived from glands isolated from proliferative and secretory tissues. In these preparations, which respond to E2 with marked elevations in PGF2 alpha output, tamoxifen and its metabolite trans-4-monohydroxytamoxifen acted as virtually pure antagonists, counteracting the E2 effect while failing to influence basal PGF2 alpha output. Consistent with its effects on other estrogen-mediated end points, trans-4-monohydroxytamoxifen was at least 10 times more potent than tamoxifen, eliminating, at a 10(-6) M concentration, almost completely the stimulatory effect of 10(-8) M E2 on PGF2 alpha production by both endometrial fragments and monolayers of epithelial cells.

Cells, Cultured↗
PubMed1986

Lipocortin output by human endometrium in vitro.

Lipocortin was found to be secreted by human endometrium incubated for 1-2 days under organ culture conditions. Levels of lipocortin in the culture medium, measured by RIA, were increased by dexamethasone (10(-8)-10(-6) M) and decreased by progesterone (10(-8)-10(-6) M). Both steroids, however, decreased prostaglandin F2 alpha (PGF2 alpha) output, also estimated by RIA. These results suggest that lipocortin does not mediate the inhibition of PGF2 alpha production evoked by progesterone. Dexamethasone may inhibit PGF2 alpha production by mechanisms involved in the inhibition by progesterone in addition to those mediated by an elevation in the levels of lipocortin, a phospholipase inhibitor.

Annexins↗
PubMed1985

Prostaglandin F2 alpha output by human endometrium under superfusion and organ culture conditions.

Specimens of proliferative and secretory human endometrium were incubated under organ culture or superfusion conditions and the levels of PGF2 alpha in the medium were measured by radioimmunoassay. Basal rates of PGF2 alpha output during short-term superfusions and long-term (1-2 day) batch incubations, performed on the same tissue specimens, were similar. Basal output of PGF2 alpha by proliferative endometrium (230-280 ng/mg protein X d) was significantly higher than that of secretory tissue under both experimental conditions. Estradiol (10(-8) M) increased PGF2 alpha output significantly (4-fold) only in secretory endometrium under organ culture conditions; Progesterone (10(-7) M) decreased it significantly (to 1/2-1/4 of the basal level) in both types of endometria during long-term incubations and in proliferative endometrium during superfusion. Glands isolated from proliferative and secretory endometrium produced PGF2 alpha during superfusion at a rate comparable to that of endometrial tissue under similar conditions. PGF2 alpha output by glands isolated from secretory endometrium increased significantly (3-fold) when estradiol was added to the superfusion medium.

Dinoprost↗
PubMed1985

In vitro effects of ovarian steroids on prostaglandin F2 alpha output by human endometrium and endometrial epithelial cells.

Correlations of the rise in prostaglandin F2 alpha (PGF2 alpha) levels in human endometrium during the menstrual cycle with changes in plasma concentrations of ovarian steroids have suggested that progesterone (P) priming of the endometrium is necessary for the stimulation of PGF2 alpha production by estradiol (E2). However, despite the absence of significant levels of P in plasma during the follicular phase of the cycle, PGF2 alpha output by epithelial cell cultures derived from proliferative endometrium was stimulated in vitro by 10(-8) M E2 at least as well as PGF2 alpha output from secretory endometrium. In addition, basal PGF2 alpha output by proliferative endometrium under organ culture conditions was significantly greater than that by secretory endometrium. Concurrent addition of P counteracted the effects of E2 in these in vitro systems. P (10(-7) M) plus E2 (10(-8) M) resulted in PGF2 alpha output as low or lower than those of control incubations of secretory and proliferative endometrium. In the epithelial cell cultures, significant net stimulation by 10(-8) M E2 occurred in the presence of 10(-6) M P, a noteworthy finding since the rise in endometrial PGF2 alpha during the luteal phase takes place when the tissue is exposed to both E2 and P. P lowered the basal output of PGF2 alpha by endometrium in organ culture, but not by epithelial cells in monolayer cultures. E2 appears to stimulate PGF2 alpha output by increasing synthesis rather than diminishing metabolism, since exogenous [3H]PGF2 alpha was metabolized to an equivalent extent by fragments of secretory endometrium or glandular epithelial cells regardless of whether E2 was added to the incubation medium. The results from this study confirm that only secretory endometrium responds to E2 in vitro by significantly increasing PGF2 alpha output. The lack of response by proliferative endometrium, when contrasted with the marked responsiveness of epithelial cells derived from this tissue, suggests that an inhibitory influence is removed during the isolation or subsequent culture of endometrial glands.

Cells, Cultured↗
PubMed1984

Effects of estriol on PGF2 alpha output by cultures of human endometrium and endometrial cells.

We have shown that the rate of release of PGF2 alpha by monolayer cultures of epithelial cells from proliferative endometrium is markedly elevated by addition of estradiol to the medium. In cultures maintained in HAM F-10 medium containing charcoal stripped calf serum, estradiol (10(-8) M) increased the levels of PGF2 alpha several fold during the second and third days in culture. Similar responses were obtained with estradiol at 10(-10) M concentration. When this system was used to compare the effects of estradiol and estriol at equal concentrations (10(-8) M), similar elevation (10-16-fold) of PGF2 alpha levels were noted during 3 consecutive days in culture. When cultures of epithelial cells derived from secretory endometrium were used for these tests, estriol was as effective as than estradiol in elevating PGF2 alpha levels in the medium. When the effects of estradiol and estriol were compared using fragments of secretory endometrium in organ culture, the increases in PGF2 alpha levels noted in the medium were about equal (2- to 10-fold) for the two estrogens at the same concentration (10(9)-10(8) M). Exposure of the tissue to either estradiol or estriol for only 1 h resulted in increases in PGF2 alpha output for the following 3 days. These results clearly show that estriol is as effective as estradiol in stimulating PGF2 alpha output by human endometrial tissue.

Cells, Cultured↗
PubMed1980

Physiological aspects of automatic physical training control by biofeedback in weightlessness.

An automatically regulated biofeedback apparatus "UN-1" is described for enabling astronauts to maintain specified levels of exercise or lower body negative pressure within acceptable limits of cardiac function. The apparatus was also used to assess the workload tolerance of cosmonauts during space flight. Under these conditions the cosmonaut was unable to exercise on the cycloergometer when his heart rate reached 140 beats/minute steady state.

Adaptation, Physiological↗
PubMed1975

Intraspecific aggressiveness after lesions of midbrain raphe nuclei in rats.

Serotonin-depleting lesions of midbrain raphe (extensive lesions located within dorsal and partly median raphe muclei) induced intraspecific agressiveness in grouped Wistar male rats but failed to increase mouse-killing behaviour. Rats which had lesions in the lateral midbrain did not display intraspecific aggression nor mouse-killing activity. These animals showed unchanged levels of both serotonin and noradrenaline in the forebrain.

Aggression↗