Biomedical subjects

G J Haluska

Publications and source records attributed to G J Haluska.

26 records · Page 2Linked to original sources

PubMed1989

The effect of relaxin infusion on prolactin and growth hormone secretion in monkeys.

To test the hypothesis that relaxin may affect pituitary hormone secretion, synthetic human relaxin was infused into cycling and pregnant rhesus monkeys. Doses ranging from 0.154-1540 ng/kg.min were calculated to achieve circulating relaxin concentrations of 1 pM to 10 nM. Low (0.154 and 1.54 ng/kg.min), intermediate (15.4 and 154 ng/kg.min), and high (1540 ng/kg.min) doses of relaxin were infused for 15 min each hour into ovulating monkeys at the midluteal phase of the menstrual cycle in two separate experiments. Serum GH and PRL were measured by RIA, and serum relaxin was determined by enzyme-linked immunosorbent assay. Relaxin was undetectable in peripheral plasma during the control saline infusion and during infusion of the lowest dose of relaxin. Serum relaxin levels reached 0.011, 0.119, 0.965, and 13.0 nM with 1.54, 15.4, 154, and 1540 ng/kg.min, respectively. Serum GH was significantly elevated over basal levels upon infusion of relaxin from 1.54-1540 ng/kg.min; however, a plateau was observed with the intermediate doses, and a decrease in the magnitude of the response was observed at the highest dose. Serum PRL increased over basal levels with 15.4 and 154 ng/kg.min, but there was no difference in the magnitude of the increase between these doses. PRL levels during infusion of the highest dose of relaxin were similar to control levels. These data suggest that relaxin can stimulate secretion of GH and PRL in cycling monkeys within a defined dose range, but that a decrease in pituitary responsiveness occurs at higher doses. One high dose of relaxin (2600 ng/kg.min) was infused for 1 h into the maternal and then the fetal circulations of chronically catheterized and tethered pregnant monkeys between 120-140 days gestation. Upon infusion of relaxin into the maternal circulation, there was a significant elevation of PRL in the mother but not the fetus. Upon infusion of relaxin into the fetus, there was no consistent change in PRL secretion in either the mother or the fetus. In conclusion, relaxin may have a heretofore undescribed role in pituitary physiology during the menstrual cycle and in pregnancy.

Animals↗

PubMed1989

[Pregnancy and labor in the mare: uterine activity and endocrinology].

Electromyographic (EMG) recordings were made during the last two weeks of pregnancy from two mares. Four bipolar EMG electrodes were implanted in the uteri of the mares; near the tubo-uterine junction and bifurcation of the pregnant horn, in the body of the uterus and near the cervix. Plasma samples were collected every 4 hours during the same period and more intensely during parturition. Estradiol 17 beta, progesterone, PGF2 alpha metabolite and oxytocin were measured by radioimmunoassay. During the last week preceding delivery, EMG activity was elevated and was greatest at night. EMG activity was further increased during the last 24 hours before delivery of the foal and reached its highest intensity for 7 to 13 hours immediately prepartum. This period of intense activity is described as stage I of parturition. EMG activity decreased to very low levels 2 to 4 hours before delivery but abruptly increased again at rupture of the choriollantois and continued through delivery when activity decreased again until delivery of the placenta. The ratio of estradiol 17 beta to progesterone (E 17 beta/P) increased through the last week prepartum due to an increase in the level of estradiol 17 beta concentrations and during the last 24 hours the change in the E 17 beta/P ratio was due to a significant decrease in progesterone. Oxytocin and PGF2 alpha metabolite increased abruptly just before rupture of the fetal membranes and there is some evidence that oxytocin increased prior to PGF2 alpha metabolite. We hypothesize that the increasing E 17 beta/P ratio allows the evolution of labor to occur during the daylight hours preceding parturition.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1988

Variation in plasma concentrations of oestradiol-17 beta and their relationship to those of progesterone, 13,14-dihydro-15-keto-prostaglandin F-2 alpha and oxytocin across pregnancy and at parturition in pony mares.

Concentrations of plasma progesterone were similar to values reported in the literature except that a significant decrease in progesterone during the last day, but before parturition, was detected by systematic, high-intensity blood sampling. Mean concentrations of oestradiol-17 beta increased sharply and significantly, plateaued for 132.8 +/- 1.5 days (mean +/- s.e.m., N = 9), then declined sharply in each mare. There was obvious variation between the mares in when these increases and decreases in oestradiol-17 beta occurred, with the events being related closely to ambient photoperiod conditions rather than to the stage of pregnancy. Concentration of 13,14-dihydro-15-keto-prostaglandin F-2 alpha (PGFM) remained at low levels (less than 400 pg/ml) until Day 200 then increased to peak pregnancy levels (greater than 2000 pg/ml) by Day 300 and remained at this value until parturition. The concentrations of oxytocin remained basal (less than 15 microU/ml) throughout pregnancy and increased only at the beginning of the expulsive stage of labour. There was an increase, although not statistically significant, in the relative concentrations of oestradiol-17 beta to progesterone beginning 3 days before parturition, with the highest value of the ratio occurring at fetal delivery. Far more striking were acute changes in PGFM and oxytocin during parturition. Maximal concentrations of PGFM (approximately 30 ng/ml) and oxytocin (greater than 200 microU/ml) were measured between rupture of the chorioallantois and the completion of delivery. Closely timed samples from one animal showed that oxytocin increased (more than 10 standard deviations of the mean levels during late pregnancy for this animal) before any change in PGFM. In another dystocic mare, both oxytocin and PGFM peaked in the initial stages of delivery but only oxytocin remained elevated until the dystocia was remedied. The results suggest that an abrupt increase in oxytocin secretion precipitates the expulsive phase of parturition in mares.

Animals↗

PubMed1987

Temporal changes in uterine activity and prostaglandin response to RU486 in rhesus macaques in late gestation.

Progesterone withdrawal as a mechanism of parturition in primates is controversial because maternal, fetal, and amniotic fluid progesterone concentrations do not decrease before parturition. We therefore studied the effects of RU486 on uterine activity and amniotic fluid prostaglandins in four rhesus macaques implanted with amniotic fluid and maternal vascular catheters and with fetal electrocardiogram and uterine electromyogram electrodes at 119 to 124 days' gestation (term = 168 days). Uterine electromyogram, intra-amniotic pressure (hourly contraction area, mm Hg.sec/hr), and fetal electrocardiogram were monitored continuously. After a stabilization period (6 to 9 days) RU486 was administered orally (20 mg/kg/day) at 1000 hours for 3 days. Uterine activity increased from basal levels (less than 4000 mm Hg.sec/hr) 8 hours after the first dose of RU486, reaching levels of 12,000 mm Hg.sec/hr. A sustained increase in uterine activity (13,000 to 30,000 mm Hg.sec/hr) was observed for 48 hours before cesarean section with little or no cervical effacement or dilatation. Increases in amniotic fluid prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha, and 11-deoxy-13,14-dihydro-15-keto-11 beta, 16 epsilon-cycloprostaglandin E2 occurred 40 hours after the onset of increased uterine activity. In contrast, amniotic fluid prostaglandins in the control animals delivering at term (n = 4) increased 24 to 48 hours before significant increases in uterine activity occurred. Control animals but not those given RU486 demonstrated a progressive nocturnal peak in uterine activity before delivery. Progesterone receptor blockade stimulates intense preterm uterine activity but not the orderly sequence of changes in prostaglandins and cervical status observed during normal parturition.

Amniotic Fluid↗

PubMed1987

Electromyographic properties of the myometrium of the pony mare during pregnancy.

Recordings of uterine electrical activity were made from 5 pregnant pony mares from Day 141 to 320 of pregnancy. Three types of activity were identified. Short, medium and long bursts were quantified as the percentage of time each occurred during the hour analysed and further categorized according to frequency, amplitude and duration. The uterus was most active during the early stages recorded and became increasingly quiescent after Day 240. Short-burst activity was greatest when the uterus was most quiescent. Long bursts showed the greatest percentage of activity until Day 220 and then decreased. Medium-burst activity was present throughout the period studied and high amplitude synchronous medium bursts peaked at Day 221-240.

Animals↗

PubMed1987

Electromyographic properties of the myometrium correlated with the endocrinology of the pre-partum and post-partum periods and parturition in pony mares.

A complete set of electromyographic recordings, plasma samples and behavioural observations were collected from 2 mares beginning 7 days pre partum, through parturition and into the early post-partum period. During the week pre partum, EMG activity was elevated, occurring 26-73% of the time. Activity was least during the day and greatest at night with no significant difference for the hours of the day or between days pre partum. During the 24 h before delivery, EMG activity was increased for 7-13 h (55-80%) during the daylight hours. EMG activity decreased 2-4 h immediately preceding delivery of the foal, with an abrupt increase at rupture of the chorioallantois. At delivery, EMG activity consisted of events containing a series of 10-13 discrete bursts of increasing amplitude occurring in rapid succession. After fetal delivery there was a reduction in activity until placental delivery followed by very long (2-22 min) trains of potentials.

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PubMedDate not supplied

Interleukin-1 beta intra-amniotic infusion induces tumor necrosis factor-alpha, prostaglandin production, and preterm contractions in pregnant rhesus monkeys.

OBJECTIVE: To describe the temporal and quantitative consequences of intra-amniotic interleukin-1 beta infusion in a nonhuman primate model. METHODS: On days 128-138 of gestation (term 167 days), four chronically instrumented rhesus monkeys (Macaca mulatta) underwent serial intra-amniotic infusions of 2, 5, and 10-20 micrograms recombinant human interleukin-1 beta. Each infusion was for 2 hours, and subsequent infusions were at least 48 hours later. Amniotic fluid was sampled serially both before and after infusion for interleukin-1 beta, tumor necrosis factor-alpha (TFN-alpha), and prostaglandin (PG) E2 and F2 alpha by specific assays, and uterine activity in each monkey was recorded continuously. RESULTS: Intra-amniotic concentrations of interleukin-1 beta rose dramatically after infusion. This rise was rapidly followed by the appearance of TNF-alpha in the amniotic cavities of all animals, with maximal levels reached 5 hours after the initiation of the infusion. Both interleukin-1 beta and TNF-alpha were rapidly cleared from the amniotic fluid and returned to baseline levels by 24-48 hours. Increases in PGE2 and F2 alpha paralleled those of the two cytokines but remained elevated for the duration of the experiments. The stimulation of uterine contractility from a pre-infusion level of 200 mmHg. seconds/hour to 6000 mmHg. seconds/hour occurred an average of 6-10 hours after interleukin-1 beta infusion. These stimulations were transient, usually abating by 22 hours after infusion, and did not result in frank labor. CONCLUSION: In the rhesus monkey, intra-amniotic infusion of interleukin-1 beta rapidly induces production of intra-amniotic TNF-alpha as well as PGE2 and F2 alpha, followed by uterine contractility. Uterine activity diminishes as cytokine levels return to pre-infusion levels, even in the presence of elevated intraamniotic PG levels. Tumor necrosis factor-alpha may act synergistically with interleukin-1 beta in the pathophysiology of cytokine-related preterm labor.

Amniotic Fluid↗

PubMedDate not supplied

Progesterone receptor localization and isoforms in myometrium, decidua, and fetal membranes from rhesus macaques: evidence for functional progesterone withdrawal at parturition.

OBJECTIVE: It is not known whether withdrawal of progesterone (P) action is a prerequisite for parturition in women or in nonhuman primates because concentrations of circulating progesterone or progesterone receptors (PR) in myometrium and decidua do not decrease before delivery. To examine this potentially important regulatory mechanism, we determined PR isoforms, PR localization, and mRNA in myometrium, decidua, and fetal membranes from rhesus monkeys during pregnancy and in spontaneous labor at term. METHODS: Gestational tissues were obtained midpregnancy (day 80-100), late pregnancy (day 130-145), and during spontaneous labor at term (day 161-167). Samples of rhesus monkey myometrium, decidua, chorion-decidua, and amnion were collected and analyzed for total nuclear and cytosolic PR by competitive binding assay. Progesterone receptor isoforms were identified and quantified by Western blot analysis, and PR mRNA was determined by a specific ribonuclease protection assay. Nuclear PR was localized by immunohistochemistry with monoclonal anti-PR (JZB39) after microwave stabilization. RESULTS: Myometrium and decidua showed no change in total PR during pregnancy and labor. Nuclear PR was not detected in fetal membranes by binding assay but was localized in amnion epithelial and mesenchymal cells and in chorion laeve cytotrophoblasts by immunohistochemistry. Staining for PR was substantially less by serial antibody dilution in fetal membranes than in decidua. Message for PR was confirmed in all tissues analyzed. A significant (P <.05) shift in the ratio of PR isoforms (from PR-B dominance at midpregnancy to PR-A dominance in labor) was observed in myometrium but not in decidua. Both PR-A and PR-B isoforms and PR nuclear staining were nearly undetectable in amnion obtained during labor. CONCLUSION: A shift to PR-A dominance in myometrium at term together with a loss of PR in fetal membranes provides evidence for a functional progesterone withdrawal mechanism, which may facilitate the initiation of parturition in primates.

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