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Biomedical subjects

M Shemesh

Publications and source records attributed to M Shemesh.

At least 19 recordsLinked to original sources
PubMed1996

The effect of feeding dried tomato vines to beef cattle.

Dried Tomato vines (DTV) are used as a feedstuff in some beef cattle in Israel, despite the literature citation that tomato vines contain potentially harmful steroid alkaloids. A small-scale feeding trial over 42 d examined possible deleterious effects of feeding DTV, compared with wheat straw, in beef cows. No differences in hematological values, serum parameters for body weight were seen between the 2 groups. Steroid alkaloid content of the DTV was not examined, but toxic levels of nitrates were found. The main practical hazard in feeding DTV would appear to be from their potentially high nitrate content.

Alkaloids↗
PubMed1995

A possible linkage between gonadal hormones, serum and uterine levels of IgG of dairy cows.

We have investigated the possible linkage between serum and uterine fluid immunoglobulin G (IgG) levels and the hormonal status of the cow. In cycling cows there was a significant (P < 0.01) drop in average (of 4 consecutive days) serum IgG levels, from 36.4 +/- 6.7 mg ml-1 during the luteal phase of the estrous cycle to 28.3 +/- 5.3 mg ml-1 during and around estrus. In prepartum cows, there was a significant drop (P < 0.01) from an average of 37.6 +/- 3.7 mg ml-1 from 5 consecutive days, i.e. 11-7 before parturition, to 28.0 +/- 5.5 mg ml-1 on the day of parturition. Total IgG in the uterine fluid ranged from 30 to 115 mg in one horn and from 24 mg ml-1 to 70 mg ml-1 in the other horn during the luteal phase, but was essentially undetectable at estrus. The drop in serum and uterine IgG occurred concomitantly with the drop in peripheral serum progesterone, from 2-3 ng ml-1 at the luteal phase, and 11-7 days before calving to less than 0.5 ng ml-1 around estrus and calving. Data suggest a possible linkage between steroid hormone and IgG levels.

Animals↗
PubMed1995

Modulation of prostaglandin synthesis in mammalian sperm acrosome reaction.

Exogenous arachidonic acid induces the acrosome reaction and the production of the prostaglandins PGE2 and PGF2 alpha in bovine spermatozoa. Exogenous PGE2 also induces the acrosome reaction and PGF2 alpha synthesis. To understand better the role of PGE2 in the induction of PGF2 alpha synthesis through modulation of phospholipase A2, inhibitors of this enzyme were used. The effects of PGE2 were blocked by phospholipase A2 inhibitors and this inhibition was reversed by addition of arachidonic acid. These data indicate that PGE2 activates phospholipase A2 to produce arachidonic acid. To determine whether protein kinase C modulates phospholipase A2 activity in this process, staurosporin, an inhibitor of protein kinase C, was used. The effect of PGE2 on PGF2 alpha production is inhibited by staurosporin and this inhibition was reversed by addition of arachidonic acid indicating that protein kinase C is involved in phospholipase A2 activation. The effect of exogenous arachidonic acid or PGE2 on the acrosome reaction is blocked by lipoxygenase inhibitors but not by inhibitors of cyclo-oxygenase, indicating that lipoxygenase products are involved in the mechanism of the acrosome reaction. The presented data shed light on the cross-talk between cyclo-oxygenase and lipoxygenase and their involvement in the sperm acrosome reaction. It is suggested that cyclo-oxygenase products modulate the activity of lipoxygenase which is a key enzyme in the mechanism leading to the acrosome reaction. Stimulation of cyclo-oxygenase to synthesize PGE2 activates phospholipase A2 to release arachidonic acid which is the substrate for lipoxygenase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosome↗
PubMed1995

Bovine cyclic endometrium contains high-affinity luteinizing hormone/human chorionic gonadotropin binding sites.

High-affinity LH/hCG binding sites have been characterized in porcine, lepine, and murine uteri. In the present study, LH/hCG binding sites were characterized in bovine endometrium. Radioreceptor assays were performed with membrane homogenates of endometrial tissues and analyzed for binding site specificity and capacity. There was little competition for receptor occupancy between hCG and ovine FSH (5%) or ovine prolactin (< 0.1%), but there was a 20% cross-reaction with eCG. There was no affinity for LH/hCG in crude membrane preparations of kidney, skeletal muscle, or vascular tissues. Concentrations of endometrial LH/hCG binding sites were determined during the bovine estrous cycle. LH/hCG receptors were found in cell preparations from Days 2-4 and 15-17 of the cycle, but not in preparations from the other stages of the cycle tested (Days 8-12, pre- and post-estrus, and ovulation). The concentration of uterine LH/hCG receptor varied during the estrous cycle, with higher values at Days 15-17 (3.1 fmol/mg protein) and lower values at Days 2-4 (1.2 fmol/mg protein). However, the binding capacity of hCG by luteal cells (9.7 fmol/mg protein) was 3-fold higher (p < 0.01) than that by endometrial tissue on any day studied. No differences in affinity constant (Ka) were seen between endometrial LH/hCG receptors (either) from Days 2-4 or 15-17) and mid-cycle luteal cells (0.60 x 10(11) M-1). Using Western blot analysis, we determined the expression of cyclooxygenase (COX) during the estrous cycle of the cow. It was found that the signal for COX was strongest at 15-17 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Oxytocin and the timing of parturition. Influence of oxytocin receptor gene expression, oxytocin secretion, and oxytocin-induced prostaglandin F2 alpha and E2 release.

Oxytocin receptor (OTR) gene expression was studied in various tissues of the reproductive tract of pregnant cows and compared with ligand binding activity. Myometrium, intercaruncular endometrium, caruncular endometrium, cotyledons and fetal membranes, as well as the uterine cervix of pregnant cows expressed the bovine OTR gene. Receptor concentrations, measured by ligand binding to crude microsomal pellets, were comparable to OTR mRNA signal strength in all instances indicating that the receptor protein formation is probably regulated at the transcriptional level. During bovine pregnancy OTR gene expression was initiated at different times depending on the tissue. The expression of the gene for OT peptide was not found in any of the bovine uterine tissues but was found in the corpora lutea at term and during parturition and then at relatively low levels. Therefore endogenous OT is derived almost exclusively from the pituitary during bovine pregnancy. OT secretion occurred in a pulsatile manner during pregnancy; a significant increase in pulse amplitude was observed during the last days before delivery and a large surge was associated with active labor and delivery. We postulate that the temporal order of OTR gene expression in the uterine and intrauterine tissues is a factor in the synchronization of the events that eventually lead to the onset of parturition. Because OT receptor mediates different actions in different tissues OT has multiple functions in the mechanism of parturition. The peptide initiates and maintains myometrial contractions, it stimulates release of PGF2 alpha from the endometrium and fetal membranes and, as demonstrated in this study, OT induces PGE2 release from cervical tissues in an OTR dependent manner. We conclude that in pregnant cows, OT participates both in the events that prepare the reproductive tract for birth and initiate the birth process.

Animals↗
PubMed1994

Gingival hyperplasia induced by calcium channel blockers: mode of action.

Gingival hyperplasia is a known side effect in patients treated with diphenylhydantoin, cyclosporin and the calcium channel antagonists. The present study proposes a mechanism by which calcium channel antagonists may induce gingival hyperplasia. The calcium antagonist induces blockage of the aldosterone synthesis in zona glomerulosa of the adrenal cortex since this pathway is calcium-dependent, cyclic nucleotide-independent. This may produce a feedback stimulation of an increase in pituitary secretion of ACTH which affects zona glomerulosa hyperplasia. This hyperplasia is merely related by accumulation of steroid intermediate products (androgens) that are transformed to testosterone because of an increase in 17-alpha-hydroxylase enzyme activity. Elevated levels of testosterone may act on the gingival cells and matrix to produce gingival hyperplasia.

Adrenocorticotropic Hormone↗
PubMed1994

Induction of cyclooxygenase and prostaglandin E2 production by the bovine pre-embryo.

A study was conducted to determine the induction of cyclooxygenase production in the cleaved and non-cleaved oocyte and to measure the secretion of prostaglandin E2 (PGE2), PGF2 alpha and tumour necrosis factor-alpha (TNF alpha) in the conditioned medium of non-mature oocytes (denuded), mature oocytes (oocyte-cumulus complex), cleaved oocytes, and non-cleaved oocytes (mature oocytes incubated in the absence of sperm). Cyclooxygenase was readily detectable in 48-h cleaved oocytes whereas the signal for the enzyme in the non-cleaved oocytes was weak or undetectable. Cyclooxygenase expression in the cleaved oocytes was transient and enzyme concentrations at the early morula stage (72 h) were low. Measurable amounts of both PGE2 and TNF alpha were secreted during the first 24 h of maturation and 6 h after fertilization, whereas PGF2 alpha was undetectable at these times. There was a dramatic enhancement in PGE2, PGF2 alpha and TNF alpha secretion 48 h after fertilization. At 72 h after fertilization, PGE2 concentrations were much lower and PGF2 alpha was again undetectable which corresponded to a low concentration of cyclooxygenase. In contrast, high TNF alpha activity continued to be detected even 72 h after fertilization. It is possible that the induction of the production of cyclooxygenase and the secretion of PGs and TNF alpha by fertilized oocytes at specific times after fertilization plays a role in the regulation of embryonic development, maternal immunological recognition of pregnancy, and the maintenance of a suitable hormonal environment for embryonic viability.

Animals↗
PubMed1994

Staurosporine stimulates progesterone production by bovine placental cells.

Progesterone (P4) production by the bovine placenta differs from that of other steroidogenic tissue in two important respects: 1) it is calcium-dependent but cyclic nucleotide-independent and 2) it is suppressed by an endogenous inhibitor for most of the life span of the placenta. This natural refractory state of the placenta can be overcome in in vitro incubations of fetal cotyledon cells by agents that increase intracellular calcium (3-isobutylmethylxanthine [MIX], calcium ionophore (A23187), addition of substrate (pregnenolone, hydroxycholesterol), and stimulators of protein kinase C (PKC) such as phorbol ester (TPA). We therefore tested, in cultures of cotyledonary cells, two compounds that have been reported to inhibit protein kinases: 1) staurosporine (STA), an inhibitor of PKC, cAMP-dependent kinase, tyrosine kinase (TK), and the epidermal growth factor (EGF) receptor TK, and 2) genistein, an inhibitor of TK. It was found that STA stimulated steroidogenesis in a dose-dependent manner in both the absence and presence of added calcium. STA (10(-9) M) stimulated at least a twofold increase in P4 production by cultured fetal cotyledon cells throughout the first half of gestation (50-130 days). EGF was also found to cause a twofold stimulation of P4 production, and the effect was additive to that of STA. Both basal and EGF- or STA-stimulated production were inhibited by genistein. In contrast, two inhibitors of PKC and PKA (H-7, H-8) had no effect on P4 production. We conclude that STA-induced steroidogenesis in the bovine placenta is not related to its reported ability to inhibit PKC, TK, or EGF receptor TK.

Alkaloids↗
PubMed1994

Localization of cyclooxygenase and production of prostaglandins in bovine spermatozoa.

Ejaculated bovine spermatozoa were examined for their capacity to synthesize prostaglandins E2 and F2 alpha (PGE2, PGF2 alpha). It was found that in the absence of exogenous substrate, arachidonic acid, basal PGF2 alpha production was less than that of PGE2. However, addition of 61 mumol arachidonic acid I-1 resulted in at least a twofold increase in PGE2 and PGF2 alpha above control values (1.3 ng and 0.3 ng per 10(8) spermatozoa, respectively). Addition of calcium and the calcium ionophore A23187 to the incubation medium did not cause a significant increase in the production of either PG. The presence of indomethacin (100-200 micrograms ml-1) caused a 50-70% inhibition of the production of both PGs. Activity of cyclooxygenase was determined by western blot analysis, using a specific polyclonal antiserum, and by fluorescence immunohistochemistry using a monoclonal antibody. The western blot displayed a clear signal for the presence of cyclooxygenase in ejaculated and epididymal spermatozoa. The immunohistochemical studies showed that the enzyme is localized in the apical region of the head, the post-acrosomal region and the mid-piece of the tail. Since the synthesis of PGs in the absence of exogenous arachidonic acid is low, the effect of melittin, a known phospholipase A2 activator, on PG production was examined. Incubation of spermatozoa with melittin produced a threefold increase in PGE2 and a sixfold increase in PGF2 alpha. Staurosporine, a protein kinase C inhibitor, inhibited the effect of melittin indicating that activation of phospholipase A2 by protein kinase C is an obligatory step in PG synthesis by bovine spermatozoa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Prostaglandin production by the oocyte cumulus complex around the time of fertilization and the effect of prostaglandin E on the development of the early bovine embryo.

The oocyte-cumulus complex (25 oocytes per 250 microL medium) produced prostaglandin-F2 alpha (PGF2 alpha) and PGE2 during maturation, immediately following fertilization and for at least 48 h after fertilization. The data suggest that PG production is important in the development of the oocyte; addition of PGE2 (5 ng mL-1) to the fertilization medium increased the rate of cleavage and groups of oocytes with low cleavage rates produced far less PG than groups with high cleavage rates. Measurement of PG in the maturation medium could therefore be a means of assessing the suitability of oocytes for fertilization.

Animals↗
PubMed1992

Dexamethasone inhibition of cyclooxygenase expression in bovine term placenta.

Since both prostaglandin (PG) F2 alpha and corticosteroids are elevated in mammals before the onset of parturition, we studied the effect of the synthetic corticosteroid dexamethasone on PGF2 alpha accumulation and cyclooxygenase (prostaglandin synthase, PGS) expression in the bovine fetal placenta. Cultures were prepared from cotyledons at different stages of gestation. The effect of dexamethasone on PGF2 alpha accumulation and PGS expression was determined by radioimmunoassay and [35S]methionine metabolic labeling followed by immunoprecipitation with specific anti-cyclooxygenase antibodies, respectively. Data demonstrate that in fetal placental cells at term, both PGF2 alpha accumulation and cyclooxygenase expression are significantly inhibited after 18 hours of dexamethasone treatment (150 nM). In contrast, neither first nor second trimester cells were sensitive to dexamethasone treatment. Dexamethasone inhibition of PGF2 alpha synthesis in fetal cells at term was abolished in the presence of RNA or protein synthesis inhibitors (actinomycin D or puromycin, 10 micrograms/ml each). Neither progesterone nor 17 beta-estradiol accumulation were affected by dexamethasone treatment at any stage of gestation. Data suggest that corticosteroids play a role in parturition through PGF2 alpha synthesis regulation by fetal placental cells. Since abnormalities during parturition e.g. retained placenta, are common following dexamethasone induction of labor in cows, we postulate that the local inhibition of PGF2 alpha accumulation by cotyledon cells after corticosteroid administration, may be involved in placental retention.

Animals↗
PubMed1992

Bovine placental progesterone synthesis: comparison of first and second trimesters of gestation.

We have previously reported that dispersed caruncle cells from cows during the first trimester of pregnancy, in comparison to caruncle cells from cows of more than 90 days of gestation, produce little progesterone (P4) and are refractory to agents that enhance steroidogenesis. To explain this refractoriness of the first-trimester cells, we determined (1) the expression of cytochrome P450 side-chain cleavage (P450scc) and its mRNA, (2) the expression of adrenodoxin, and (3) 3 beta-hydroxysteroid dehydrogenase activity. We first determined P4 and pregnenolone (P5) production by dispersed caruncle cells from the two gestation periods using RIA. It was found that P4 synthesis by bovine maternal caruncle cells was low or undetectable in the first trimester but increased more than 10-fold in the second trimester of gestation. Addition of 25-OH-cholesterol (5 micrograms/ml) to second-trimester maternal cells increased P5 production, but no effect was observed in first-trimester cells. With [3H]P5 used as substrate, analysis of metabolites on thin-layer chromatography indicated that first-trimester maternal cells synthesized a small amount of P4 (3.02% of total radioactivity) compared to second-trimester cells (16.4%). A readily detectable amount of 17 alpha-OH-P5 was produced by the second-trimester cells (5.02%) but not by the first-trimester cells (0.6%). No other metabolites could be characterized (less than 0.5%). Cytochrome P450scc expression and its mRNA and adrenodoxin content were determined by use of Western blot or dot-blot techniques. Proteins and mRNA were detected in maternal tissues of first and second trimesters of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗
PubMed1992

Regulation of steroidogenesis in the bovine placenta.

As pregnancy progresses in the cow, the secretory activity of the corpus luteum is markedly diminished. This reduced secretion is due to a decline in the number of viable luteal cells as well as reduction in the secretory activity and responsiveness of the cells to trophic agents. The principal extra-ovarian source of progesterone (P4) by mid-gestation therefore appears to be the placenta. Uniquely this P4 biosynthesis is cyclic-nucleotide independent, but the Ca+2 dependent. It therefore appears that the Ca+2 second messenger and protein kinase C systems are responsible for regulation of sterol biosynthesis in the cow placenta. Dispersed bovine caruncle cells from the first trimester of pregnancy in comparison to caruncle cells of older than 90 days of gestation produce little P4 and are refractory to agents which enhance placental steroidogenesis. In order to explain this refractoriness of the first trimester cells, we determine (1) the expression of P450scc and its mRNA and (2) the expression of adrenodoxin. It was found that P4 synthesis by bovine maternal caruncle cells was low or undetectable in the first trimester but increased more than 10-fold in the second trimester of gestation. Addition of 25-OH-cholesterol to second trimester maternal cells increased P5 production but no effect was observed in first trimester cells. Cytochrome P450scc and its mRNA and adrenodoxin content were determined using Western blot or dot-blot techniques. Both proteins and the mRNA were detected in maternal tissue of first and second trimesters of gestation. In conclusion low P4 levels synthesized by first trimester maternal cells are not due to the absence of either cytochrome P450scc or adrenodoxin protein or production of P450scc mRNA. The data suggest that the refractoriness of the maternal caruncle cells during the first trimester is the result of post-translational regulation.

Adrenodoxin↗
PubMed1991

Cytokine involvement in oocytes and early embryos.

OBJECTIVE: The early events of reproduction involve a carefully modulated complex system of oocyte maturation, fertilization, and proliferation. The aim of the study was to measure the presence of cytokines, namely interleukin 1 (IL-1), interleukin 6 (IL-6), colony-stimulating factor 1 (CSF-1), and tumor necrosis factor (TNF) in the conditioned medium (CM) of the oocytes, granulosa cells, cumulus cells, one to eight-cell embryos and sperm. DESIGN: The material was obtained from men and women undergoing in vitro fertilization therapy. MAIN OUTCOME MEASURES: We hypothesized that cytokines might affect embryonic growth and differentiation as they show a pleotropic effect on immune cells. RESULTS: All these cytokines are present in significant quantities in the CM and were shown to be expressed in a sequential manner; thus, some are present in the oocyte and its vestment, the corona-cumulus complex (IL-1, IL-6, and CSF-1), whereas TNF appears only at the stage of six to eight-cell embryos. Inflammatory cytokines could not be detected in sperm samples. CONCLUSIONS: It is possible that these cytokines have a role in the regulation of embryonic development, maternal immunological recognition of pregnancy, and maintenance of proper hormonal environment.

Cytokines↗
PubMed1991

Dexamethasone inhibition of prostaglandin production in human term placental cells is protein and ribonucleic acid synthesis dependent.

A key enzyme in the regulation of prostaglandin (PG) synthesis is PG synthase (PGS; cyclooxygenase), which converts arachidonic acid to PGs. Since both PGs and glucocorticoids are elevated before parturition, we studied the regulation of dexamethasone (DEX; 150 nM) on PGF2 alpha synthesis and PGS expression in human placental cells in vitro. Both first trimester and term placental cells were used. DEX reduced PGF2 alpha synthesis in human term placental cells, in contrast to first trimester cells which were unaffected by the same treatment. DEX inhibition of PGF2 alpha production by term placental cells was time and dose dependent. PGS expression was analyzed by [35S]methionine metabolic labeling and immunoprecipitation using polyclonal antibodies developed in rabbits against ram seminal vesicle PGS. DEX reduced PGS expression in term placental cells, but not in first trimester cells. In contrast to the effect of DEX on PGF2 alpha, progesterone and estradiol production by cells were unaffected at any stage of gestation examined. DEX inhibition of PGF2 alpha synthesis required de novo biosynthesis of RNA and proteins. These results suggest 1) corticosteroids play a role in the regulation of placental PG synthesis during parturition; 2) the inhibition of PG synthesis and PGS expression by glucocorticoids is RNA and protein biosynthesis dependent; and 3) induction of labor by glucocorticoids is not directly related to changes in placental progesterone or estradiol biosynthesis.

Arachidonic Acid↗
PubMed1990

Granulosa cells as a source and target organ for tumor necrosis factor-alpha.

Tumor necrosis factor (TNF-alpha), a 17 kDa cytokine, is a product of activated macrophages which was recently shown to be produced by rat and bovine granulosa cells. In the present work, human granulosa cells derived from preovulatory follicles were used. It was demonstrated that human granulosa cells produce TNF-alpha (5-10 units/300,000 cells per 15 h). This production was increased by addition of follicle-stimulating hormone or by a combination of human chorionic gonadotrophin and CSF to the culture media. TNF was also found in bovine follicular fluid and the concentration was higher in the periovulatory than mid-cycle follicles. TNF-alpha was found to increase prostaglandin F-2 alpha production by human granulosa cells (P less than 0.001). We conclude that granulosa cells are both a source and target organ for TNF-alpha.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

Production and regulation of progesterone in bovine corpus luteum and placenta in mid and late gestation: a personal review.

In late pregnancy the secretory activity of the corpus luteum of the cow is markedly diminished. This reduced secretion is due to a decline in the number of viable luteal cells as well as reduction in the secretory activity and responsiveness of the cells to trophic agents. The principal extra-ovarian source of progesterone in late gestation appears to be the placenta, especially the fetal cotyledon, which was shown to produce progesterone throughout gestation. Uniquely, this progesterone biosynthesis is cyclic-nucleotide independent, but Ca2+ dependent. It therefore appears that the Ca2(+)-second messenger and protein kinase C systems are responsible for regulation of sterol biosynthesis in the cow placenta.

Animals↗