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Biomedical subjects

W B Currie

Publications and source records attributed to W B Currie.

At least 37 records · Page 2Linked to original sources

Effects of N-acetylimidazole on oxytocin binding in bovine mammary tissue.

The effects of N-acetylimidazole on specific binding of oxytocin to microsomal fractions of bovine mammary gland were studied. N-acetylimidazole suppressed oxytocin binding, with time and concentration dependence. Decreased oxytocin binding activity appeared to be due to decreased affinity of the hormone for its receptor. Acetylation of oxytocin, rather than of oxytocin receptors, seemed to be responsible for the decreased binding.

Acetylation↗

Endocrine and histologic correlates of the dynamics of the metacarpal growth plate in growing rams.

The objective was to study control of mature size by characterizing metacarpal growth plate closure in relation to relevant bone growth-regulating hormones in two breeds exhibiting distinct differences in mature frame size. Thirty-four Suffolk and 34 Dorset ram lambs were slaughtered in pairs within breed at birth, weaning and monthly intervals until 420 d and then bimonthly to 600 d. Plasma growth hormone was depressed to undetectable levels due to the high-energy, ad libitum-fed diet. Plasma insulin-like growth factor-I (IGF-I) rose over the growth period from 116 ng/ml (newborn Suffolk) to a high of 451 ng/ml (420-d Dorset); it appeared to peak at approximately 400 d and then declined to a stable level. Dorsets consistently exhibited higher IGF-I levels. The thyroid hormones exhibited no apparent age association. An age-associated rise was detected for testosterone, but not for estradiol. Mature metacarpal lengths were estimated to be 147.2 and 127.4 mm for Suffolks and Dorsets, respectively. Ninety-five percent of mature length was attained in Suffolks by 226 d and in Dorsets by 165 d. Growth plates, however, did not begin to appear closed until 390 d and closure was not complete in all animals until 480 d, suggesting that metacarpal growth rate was dissociated temporally from growth plate closure. Although growth plate closure likely is controlled by the endocrine system, there were no apparent relationships between circulating hormones and growth plate width, age at closure or zonal divisions within the growth plate, suggesting that the growth plate experiences a very different hormonal environment than what can be measured in the circulating blood.

Animals↗

Chronic heat stress and prenatal development in sheep: I. Conceptus growth and maternal plasma hormones and metabolites.

Pregnant ewes were chronically exposed to thermoneutral (TN; 20 degrees C, 30% relative humidity) or hot (H; 40 degrees C 9 h/d, 30 degrees C 15 h/d, 40% relative humidity) environments between d 64 and 136 to 141 of pregnancy. They were sampled for blood at 14-d intervals during this period for measurement of plasma metabolites and hormones, then slaughtered and dissected to measure conceptus weights, dimensions and fetal organ weights. Rectal temperatures of H ewes were elevated .3 to 1.0 C degrees above those of TN ewes throughout the experiment. Voluntary feed intakes were not altered by heat exposure except after 120 d of pregnancy, when feed intake was about 25% lower (P less than .10) by H than by TN ewes. Blood 3-hydroxybutyrate concentrations were not affected by heat, but plasma glucose concentrations were greater in H than in TN animals after 120 d (P less than .05). Placental weight, reduced by 54% (P less than .001) by heat exposure of ewes, was correlated positively with fetal weight and correlated negatively with fetal/placental weight ratio, fetal brain/liver weight ratio and fetal relative heart weight. Late in pregnancy, plasma concentrations of progesterone, cortisol and placental lactogen were reduced (P less than .01) in H ewes, whereas triiodothyronine levels were markedly lower (P less than .03) at all stages of pregnancy. Plasma concentrations of prolactin were elevated dramatically (P less than .01) and a modest increase (P less than .03) in somatotropin levels was recorded in H ewes. These results are consistent with our hypothesis that heat-induced fetal growth retardation is secondary to a primary reduction in placental growth; this could be mediated partly by reduced peripheral activity of thyroid hormones. Heat-induced reductions in secretion of progesterone and ovine placental lactogen more likely were a consequence than a cause of placental stunting.

Animals↗

Dietary calcium and metacarpal growth in ewes.

The effects of excess dietary calcium on bone growth were quantified in 44 ewes fed ad libitum diets that contained one of four levels of dietary calcium (0.37, 0.56, 1.13 and 1.80%) and 0.42% phosphorus. Animals were slaughtered at one of six ages, circulating concentrations of hormones and minerals were measured and bone morphometry was evaluated. None of the diets impaired normal bone growth of the metacarpal as evaluated by overall length, cortical index and growth plate width. Circulating plasma concentrations of calcium and gastrin increased as dietary calcium levels increased, but all values were within the normal range for sheep. Plasma phosphorus was unaffected by the level of dietary calcium. Diet had no affect on T3, T4 or estradiol-17 beta. Age significantly (P less than 0.05) affected the metacarpal length, growth plate width and circulating calcium and phosphorus. The metacarpal in these ewes was 95% of mature length by 172 d of age. Attainment of mature length preceded growth plate closure by slightly over 300 d. These results demonstrate that elevated dietary calcium levels do not adversely influence bone growth and that the presence of an intact growth plate does not infer that further bone growth will occur.

Age Factors↗

Endocrine changes, with special emphasis on oestradiol-17 beta, prolactin and oxytocin, before and during labour and delivery in goats.

Jugular plasma concentrations of oestradiol-17 beta, prolactin, progesterone and 13,14-dihydro-15-keto-prostaglandin F-2 alpha (PGFM) were measured at 2-h intervals during the last 4 days of pregnancy in 6 goats. During advanced labour and delivery, samples were obtained more frequently and assayed for oxytocin. The animals were housed in a barn with continuous dim lighting. A distinct pattern of oscillation in prolactin concentrations, with peaks during the late afternoon, was apparent during the last 3 days. Geometric means of peak concentrations doubled each day and became of longer duration; night-time nadir values remained low except during the last night before parturition. A progressive increase in oestradiol-17 beta, with mean levels doubling every 36 h, was apparent during the last 3 days. There was no sharp pre-partum increase in oestradiol-17 beta. Correlated (r = 0.83) with the increase in oestradiol-17 beta was a gradual increase in PGFM and when the latter reached approximately 1000 pg/ml, the non-reversible decline in progesterone reflecting pre-partum luteolysis occurred. Subsequent changes in PGFM related closely to an approximately 20-fold increase in the ratio of oestradiol-17 beta to progesterone until maximal PGFM levels of 26.5 +/- 4.2 ng/ml were reached at delivery. Basal concentrations of oxytocin (8-15 microU/ml) were measured before the last 60 min and markedly higher, though erratic, concentrations were detected at various times before appearance of the allantochorion. Maximal oxytocin values (range 180-1570 microU/ml) occurred within minutes before or after delivery of the first fetus. The results suggest that increased pre-partum production of oestradiol-17 beta, in addition to provoking sufficient release of prostaglandins to cause luteolysis, may modulate either the sensitivity or set-points for an endogenous rhythm in prolactin secretion at the end of pregnancy. The nature of the oxytocin changes suggest that, after labour has evolved sufficiently, delivery is precipitated by an abrupt increase in oxytocin secretion.

Animals↗

Fetal development, and placental and maternal plasma concentrations of progesterone in the little brown bat (Myotis lucifugus).

Progesterone concentrations measured in plasma samples from 280 bats captured during pregnancy or early lactation were related to fetal attributes indicative of stage of pregnancy. Fetal weight increased exponentially from 40 mg at crown-rump length of 6 mm to 2000 mg at 23 mm (term). Fetal weights at term accounted for up to 35% of the weight of intact pregnant animals. Progesterone concentrations increased from less than 5 ng/ml at 2 mm estimated crown-rump length to plateau values of approximately 65 ng/ml (geometric means) from 16 mm crown-rump length until the most advanced stages of pregnancy. Mean concentration in 8 post-partum bats, most of which were actively lactating, was 8.4 ng/ml; 11.6 ng/ml was measured in one animal that was carrying a wet neonate when sampled yet was still pregnant when captured 5 h earlier. Placental concentrations of progesterone ranged from 43 to 964 ng/g wet weight of tissue and mean values increased in a similar fashion though were about 4-fold greater than changes in plasma concentrations of the steroid. The concentrations in placental tissue were at least 15- to 20-fold higher than could be expected from blood contamination, indicating that placental steroidogenesis is likely to occur in this species.

Animals↗

Elevated concentrations of 13,14-dihydro-15-keto-prostaglandin F-2 alpha in maternal plasma during prepartum luteolysis and parturition in dogs (Canis familiaris).

Concentrations of progesterone and of 13,14-dihydro-15-keto-prostaglandin F-2 alpha (PGFM) were measured in plasma collected from 6 bitches every 3 h starting 2.8-4.6 days before parturition (birth of first pup) and continuing until 0.4-0.8 days post partum, and in additional samples collected less frequently. Progesterone concentrations at 48, 24, 12 and 3 h pre partum averaged 2.8 +/- 0.3, 2.2 +/- 0.4, 1.0 +/- 0.3 and 0.7 +/- 0.2 ng/ml. At those times PGFM values averaged 380 +/- 80, 800 +/- 220, 1450 +/- 450 and 1930 +/- 580 pg/ml, respectively. Mean concentrations of PGFM increased about 2.5-fold between 48 and 15 h pre partum in association with the onset of luteolysis, and then increased another 2.5 times before parturition as progesterone fell to nadir values. Peak levels of PGFM ranged from 1060 to 7150 pg/ml (2100 +/- 600 pg/ml) and occurred within 1-9 h after the birth of the first pup and before the birth of the last pup. These results suggest that prepartum luteolysis in dogs is initiated by increases in maternal concentrations of PGF, and that progesterone withdrawal causes a further increase in PGF which completes luteolysis and provides a major portion of the uterotonic activity causing expulsion of pups.

Animals↗

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↗

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↗

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.

Animals↗

Variation in the oxytocin content of caprine corpora lutea across the breeding season.

Ovarian tissues were obtained from cyclic goats during the early, mid and late breeding season. Immunoreactive oxytocin was measured by RIA in tissue extracts after chromatography on octadecylsilica cartridges. Luteal oxytocin concentrations were significantly greater during the early breeding season than during the mid or late breeding season. Oxytocin is luteolytic in goats. High concentrations of luteal oxytocin may be related to the high incidence of short estrus at the onset of the breeding season.

Journal Article↗

Uterine steroid receptor changes associated with progesterone withdrawal during pregnancy and pseudopregnancy in rabbits.

Cytosolic and nuclear progesterone (P) and estrogen (E) receptors (PR and ER, respectively) were measured in uterine tissues of rabbits at the end of pregnancy (days 25, 27, 29, 30, and 31 and 0-10 h postpartum) and pseudopregnancy (days 13 and 18). At both times, plasma P concentrations fell dramatically after a period of prolonged elevation, effecting changes in uterine function. Plasma concentrations of P remained elevated until day 29 of pregnancy and then fell continuously until postpartum, whereas plasma estradiol levels did not change. The numbers of nuclear ER and PR were constant from days 25-29. Concomitant with the fall in plasma P on day 30, levels of nuclear ER and PR doubled and remained elevated on day 31 and postpartum. In all cases, the numbers of nuclear receptors were negatively correlated with P concentrations. The number of cystosolic ER in the myometrium increased on day 30 of pregnancy and remained elevated on day 31 and postpartum. Although levels of cytosolic ER in the endometrium appeared to rise similarly, the change was not significant. The number of cytosolic PR in endometrium and myometrium did not change significantly. Between days 13 and 18 of pseudopregnancy, plasma P declined while plasma estradiol remained constant, as during pregnancy. At this time, cytosolic PR increased 4-fold, and nuclear PR doubled. Nuclear ER also increased between days 13 and 18, but the apparent increase in cytosolic ER was not significant. These data suggest that receptors for both steroids increase as the ratio of plasma estradiol to P increases at the end of pregnancy and pseudopregnancy. Surprisingly, nuclear PR levels are highest at term, when the influence of P in suppressing myometrial activity and preventing the onset of labor is removed. Thus, in the rabbit, the level of PR does not directly reflect the physiological response to P.

Animals↗

Changes in the responsiveness of adrenal cells from foetal goats at different times during pregnancy.

To understand the factors responsible for the increased pre-partum output of cortisol from the adrenal glands of the goat foetus, we measured changes in responsiveness to ACTH in vitro of dispersed adrenal cells from foetal goats of various gestational ages and we determined the output of cortisol (F) and corticosterone (B) in the presence of exogenous progesterone (P4) and 17 alpha-hydroxyprogesterone (17 alpha-OHP4). The increment in F output after ACTH increased 5-fold between day 100 and days 147 or 154 (term). This increase was not associated with changes in the ED50 for ACTH stimulation of F output. The basal and ACTH-stimulated output of F was similar to that of B at day 100 but 5-7 times greater than that of B at day 154. There was a significant effect of ACTH on P4 output on days 77, 100 and 147 but net utilization of P4 by the cells at term. The ratio of exogenous P4: 17 alpha-OHP4 converted to F varied with gestation and increased from 0.11 at day 100 to 0.99 at day 154. Exogenous P4 was converted to B at all stages of pregnancy. We conclude that in the goat there is an increase in the responsiveness of foetal adrenal cells to ACTH between day 100 of gestation and term. One factor associated with this change in adrenal responsiveness may be an increase in the activity of the enzyme 17 alpha-hydroxylase.

17-alpha-Hydroxyprogesterone↗

Hormonal effects on partitioning of nutrients for tissue growth: role of growth hormone and prolactin.

The growth process exemplifies changes in the priorities of different tissues for available nutrients according to a developmental program. We propose that a higher order of endocrine regulation over and above that provided by homeostatic mechanisms directs the flow of nutrients to support the physiological or developmental process of highest prevailing priority. The term homeorhesis is applied to this regulatory phenomenon and is distinguished from the more familiar concept of homeostasis. The documented actions of growth hormone and prolactin as somatotrophic agents are discussed and their candidacy as likely homeorhetic vectors is proposed. Certain shortcomings in the quality of available hormone preparations and inconsistencies between potencies in various tests performed in vitro and in vivo are noted. We question the appropriateness of the use of experimental routines suited to exploring acute metabolic phenomena in acquiring a deeper understanding of the long-term process of growth. Despite the varied nature of supportive data, growth hormone, prolactin, and the closely related placental somatomammotropin exhibit the desired properties of homeorhetic hormones--they direct the flow of nutrients to the process of highest priority, partly by coordinating nutrient utilization by competing tissues.

Adipose Tissue↗

Enhanced excitability of the uterus of the pregnant rabbit by imidazole stimulation of cyclic AMP phosphodiesterase.

Imidazole, at concentrations between 10(-3) and 10(-2) M, exerts a profound stimulatory effect on rabbit uterine strips obtained during pregnancy and studied isometrically in vitro. The action is not duplicated by N-alkylimidazoles which have greater potency as inhibitors of thromboxane synthetase but the effect of imidazole was antagonized by isoproterenol or theophylline. Biochemical analysis indicated that imidazole at concentrations greater than 5 x 10(-4) M stimulated both high and low affinity forms of cyclic AMP phosphodiesterase. The uterus of pregnant rabbits is profoundly refractory to any kind of pharmacological stimulation and the effects of imidazole, acting to stimulate phosphodiesterase, suggest that the integrity of the adenyl cyclase-cyclic AMP-protein kinase system is a necessary requirement for this organ to remain quiescent during pregnancy.

3',5'-Cyclic-AMP Phosphodiesterases↗

Partitioning of nutrients during pregnancy and lactation: a review of mechanisms involving homeostasis and homeorhesis.

Control of metabolism during pregnancy and lactation involves two types of regulation-homeostasis and homeorhesis. Homeostasis control involves maintenance of physiological equilibrium or constancy of environmental conditions within the animal. Homeorhesis is the orchestrated or coordinated control in metabolism of body tissues necessary to support a physiological state. Regulation of nutrient partitioning during pregnancy involves homeorhetic controls arising from the conceptus. This assures growth of the conceptus (fetus and fetal membranes) and gravid uterus as well as development of the mammary gland. With the onset of lactation many--perhaps even most--maternal tissues undergo further adaptations to support rates of lipogenesis and lipolysis in adipose tissue are examples of important homeorhetic controls of nutrient partitioning that are necessary to supply mammary needs for milk synthesis. The interactions between homeorhesis and homeostasis during pregnancy and lactation and possible endocrine control are discussed. While not definitively established, roles for placental lactogen and prolactin are attractive possibilities in homeorhetic regulation of maternal tissues to support pregnancy and the initiation of lactaion, respectively.

Adipose Tissue↗