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Biomedical subjects

G Jenkin

Publications and source records attributed to G Jenkin.

At least 73 records · Page 4Linked to original sources
PubMed1985

Inhibition of progesterone secretion by a 3 beta-hydroxysteroid dehydrogenase inhibitor in late pregnant sheep.

The role of progesterone in the initiation of parturition in the sheep is unclear. Whether a decrease in plasma progesterone is the essential prerequisite for the initiation of parturition or whether other factors also maintain uterine quiescence until delivery is not known. The effect of withdrawal of progesterone on the initiation of parturition has been investigated by intravenous administration of trilostane, a 3 beta-hydroxysteroid dehydrogenase delta 5-4 isomerase inhibitor, to late pregnant sheep. Twenty-five or 100 mg trilostane caused a precipitous decrease in plasma progesterone to about 30% of preinjection levels. Progesterone remained depressed for up to 7 days after treatment. 13,14-Dihydro-15-keto-prostaglandin F2 alpha (PGFM) became elevated between 7 and 36 h after trilostane injection but gradually returned to preinjection levels during the subsequent 36 h, at a time when plasma progesterone was still depressed. Four of 11 animals treated with 100 or 200 mg trilostane aborted prematurely at a time when plasma PGFM was maximal and plasma progesterone minimal. There were no consistent changes in plasma estradiol-17 beta or ovine placental lactogen concentrations after treatment with trilostane. It is suggested that a decrease in plasma progesterone will cause a transient increase in plasma PGFM concentrations which can lead to the premature initiation of parturition. In some instances the myometrium does not appear to respond to the elevated PGFM concentrations even when the estrogen:progesterone ratio is elevated by a decrease in plasma progesterone.

3-Hydroxysteroid Dehydrogenases↗
PubMed1985

Induction of premature delivery in sheep following infusion of cortisol to the fetus. I. The effect of maternal administration of progestagens.

Premature induction of delivery in fetuses infused with graded doses of cortisol was brought about in 123.5 +/- 7.7 h (mean +/- SEM, n = 6) after the start of cortisol infusion. This treatment caused a rise in fetal plasma cortisol similar to that observed at normal delivery. Maternal and fetal progesterone and 20 alpha-dihydroprogesterone concentrations decreased to basal levels during infusion of cortisol to the fetus. Induction of premature delivery was delayed or prevented by concomitant treatment of the ewe with progestagen. Maternal intramuscular injection of 100 mg progesterone, 2 times daily, prevented delivery in four of four ewes treated during the time that cortisol was infused into the fetus (11-13 days). Maternal plasma progesterone and 20 alpha-dihydroprogesterone concentrations were maintained during this period, but fetal plasma progesterone concentrations decreased to the same extent as in the fetuses infused with cortisol alone. A single intramuscular injection of 250 mg of medroxyprogesterone acetate to ewes on the day before commencement of infusion of cortisol to the fetus prevented delivery in four of six ewes during the time that cortisol was infused for 9, 13, 14, and 15 days, respectively. One ewe delivered a live lamb at 133.5 h and another at 147.7 h after the start of infusion of cortisol to the fetus. Maternal and fetal plasma cortisol, progesterone, and 20 alpha-dihydroprogesterone concentrations were similar to those observed during infusion of cortisol alone to the fetus. Although fetal cortisol concentrations rose in a similar fashion, and to a similar extent, in all three groups during infusion of cortisol to the fetus, fetal 11-desoxycortisol concentrations only rose above basal levels close to the time of delivery in cortisol-infused fetuses or, in the progestagen-treated groups, when the fetus showed signs of being stressed.

20-alpha-Dihydroprogesterone↗
PubMed1984

Relationship between electrical activity of the uterus and surgically isolated myometrium in the pregnant and nonpregnant ewe.

Rhythmic contractions occur in the sheep uterus at oestrus and during pregnancy from about 65 days to term (145 days). To define factors responsible for these contractions we have examined and quantified the degree of synchronization of electrical activity in the uterus and isolated segments of myometrium in 3 types of experiments. In the first, a segment of myometrium was totally separated from the uterus. After a period of 9-16 days the isolated tissue developed a typical pattern of uterine activity which showed no significant degree of synchronization with EMG bursts in the body of the uterus. During labour, the isolated tissue showed changes in activity similar to those observed in the uterus. In the 2nd experiment, the tubal end of one of the uterine horns was severed from the uterus, but a connection was retained with the uterus via the oviduct and ovarian blood vessels. Activity in the partly isolated segment remained in synchrony with the uterus. In a 3rd experiment, impulse propagation through nerves and smooth muscle to the tip of a horn was disrupted by severing 'the tip' from the uterus while its blood supply from the ovarian vessels was retained. The blood vessels were momentarily frozen, and denervation confirmed by monoamine histofluorescence. In 5 out of 6 animals the operated tissue showed activity that was not synchronous with the rest of the uterus. These data indicate that: (1) isolated uterine muscle in vivo has rhythmicity resembling that of intact myometrium and (2) systemic or local circulating factors are not responsible for synchronizing uterine activity before parturition, although circulating factors do play a major role in increasing the uterine activity which occurs at parturition and at oestrus, and (3) hydraulic continuity between different regions of the uterus is not essential for maintaining co-ordinated activity.

Adrenergic Fibers↗
PubMed1984

Induction of transient functional luteolysis in cyclic sheep by a 3 beta-hydroxysteroid dehydrogenase inhibitor.

The mechanism by which prostaglandin F2 alpha terminates luteal function in the sheep is unclear even though it is used extensively in animal husbandry. At the time of luteal regression, a decrease in 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity is apparent in the corpus luteum, but it is not known whether the decrease in enzyme activity is the primary cause of structural luteolysis. The effect of trilostane, a 3 beta-HSD inhibitor, on luteal function and morphology has therefore been investigated. Intravenous injection of trilostane in the mid-luteal phase of the oestrous cycle caused a decrease in ovarian tissue progesterone content. A transient decrease in peripheral and utero-ovarian vein plasma progesterone was observed but there was no significant effect on the length of the luteal phase of the cycle. There was no significant change in plasma 13,14-dihydro-15-oxo-prostaglandin F2 alpha during the period when plasma progesterone was depressed. Morphological examination of the corpora lutea revealed a decrease in the concentration of electron-dense granules without any other features of impending luteal regression. When plasma progesterone was reduced for more than 10 h by two injections of trilostane 4h apart, there was again no subsequent effect on the length of the oestrous cycle or on the return to oestrus. Plasma progesterone returned to preinjection levels within 24 h of injection. This evidence suggests that competitive inhibition of 3 beta-HSD activity, per se, is ineffective in bringing about structural luteolysis.

3-Hydroxysteroid Dehydrogenases↗
PubMed1983

Ultrastructural evidence of variation in the number of secretory granules within the granulosa cells of the sheep corpus luteum.

The granulosa luteal cells of the sheep corpus luteum secrete their hormonal products by exocytosis of granules. Electron micrographs of randomly selected granulosa cells from nine corpora lutea at day 10 of the oestrous cycle were examined to obtain the cellular density of these granules. From the area of the cell, calculated using an x-y digitiser, and the number of granules observed, the number of intracellular secretory granules per microns 3 of luteal cell cytoplasm was calculated. There was a large variation in the number of granules per cell within the same corpus luteum and between corpora lutea taken at the same stage of the cycle. The number of intracellular granules in nine corpora lutea varied from 2.12 +/- 1.05 granules per microns 3 (mean, SD, n = 30) cells to 0.36 +/- 0.18 granules per microns 3 (mean, SD, n = 26). These morphological data suggest that the variation in granule synthesis in individual cells may contribute to the variation in hormone content of corpora lutea at the same stage of the cycle, and the episodic release of hormone into the plasma.

Animals↗
PubMed1983

The importance of prolactin for initiation of lactation in the pregnant ewe.

A single injection of ergocryptine (0.5 mg/kg liveweight) given to ewes 0.5-20 days prepartum or two injections (0.5 mg/kg liveweight per injection) given c. 30 and 10 days prepartum reduced concentrations of plasma prolactin to negligible (less than 5 ng/ml) values for 4 weeks after parturition, but did not affect concentrations of growth hormone and placental lactogen. Milking of treated ewes had no effect on concentrations of plasma prolactin during the first 4 weeks of lactation, but concentrations of growth hormone were increased during the 10-20 min period after milking. The half-life of prolactin in plasma was estimated as 21 min. In spite of the dramatic effect of ergocryptine on plasma prolactin all treated ewes secreted copious quantities of milk of normal composition. Mean daily yields of ewes treated with ergocryptine were not significantly different (P greater than 0.05) from those of untreated control ewes, but the mean +/- s.e.m. of total milk production over the first 3 weeks of lactation for ergocryptine-treated ewes was significantly lower (P less than 0.05) than that of control ewes (9.5 +/- 1.11 v. 14.1 +/- 1.20 kg milk). The results suggest that prolactin is not an essential component of the lactogenic and galactopoietic complexes of hormones in the ewe.

Animals↗
PubMed1983

The interaction of human endometrial and myometrial steroid receptors with danazol.

The affinity of danazol for oestrogen, androgen and progesterone receptors in human endometrium and myometrium was determined, to study the mechanism of action of this drug in the treatment of endometriosis. The ability of danazol to combine with each of the three types of receptor was similar in both endometrium and myometrium. The capacity of danazol to compete with oestradiol-17 beta for the oestrogen receptor was very low (1.72 +/- 0.48 X 10(-3%) cross reaction, mean +/- SEM) and danazol, at the maximum concentration used, was unable to saturate the receptor; but danazol's ability to compete with progesterone for its receptor was considerably higher (8.41 +/- 1.65% using progesterone, 1.95 +/- 0.41% using R5020) and was saturable. Danazol was also able to displace dihydrotestosterone from the cytosol androgen receptor (6.29 +/- 1.82% cross reaction). The association constant of oestradiol for the endometrial and myometrial oestrogen receptors was 2.19 X 10(9)M-1 and 7.45 X 10(9)M-1 respectively, while that of progesterone and dihydrotestosterone for their receptors was similar in endometrium and myometrium (mean 0.25 +/- 0.06 X 10(9) M-1 and 3.62 +/- 1.67 X 10(9) M-1 respectively). Using R5020, the association constant for the myometrial progesterone receptor was 2.50 +/- 0.73 X 10(9) M-1. We conclude that, in view of the high circulating levels of danazol present in patients being treated for endometriosis, it is possible that danazol may bind to, and partly saturate, endometrial and myometrial oestrogen, progesterone and androgen receptors during treatment. An explanation may thus be provided for some of the diverse actions of this drug.

Binding, Competitive↗
PubMed1983

Hormonal changes at oestrus, parturition and post-partum oestrus in the tammar wallaby (Macropus eugenii).

Concentrations of progesterone, prolactin, LH and 13,14 dihydro-15-keto-prostaglandin F2 alpha (PGFM) were measured in plasma of eight tammar wallabies at 8-hourly intervals during the end of pregnancy and post-partum oestrus initiated by removing the pouch young, and during the end of the oestrous cycle, similarly initiated. In the non-pregnant cycle oestrus occurred 29.7 +/- 0.7 (mean +/- S.E.M.) days after initiation of the cycle, was preceded by a slow decline in progesterone concentration from 1.6 nmol/l to less than 0.64 nmol/l and was followed by a preovulatory peak of LH 5.3 +/- 3.9 h later. In the pregnant cycle birth occurred 26.1 +/- 0.2 days after removing the pouch young and was followed 8.0 +/- 2.1 h later by oestrus and 16.0 +/- 2.5 h by an LH peak. The latter events thus occurred 3.2 days earlier in the pregnant than in the non-pregnant cycle. Parturition coincided with a very rapid decline in progesterone and a transient high peak of prolactin. In two females sampled less than 25 min after parturition there was a transient peak of PGFM but in all others the concentrations of PGFM remained basal throughout. It is suggested that the fetus and/or placenta is involved in both the premature decline in progesterone and the initiation of parturition and that onset of oestrus and ovulation, being a consequence of a decline in progesterone, are therefore also determined by the fetus.

Animals↗
PubMed1983

Ovine placental lactogen concentrations during premature delivery induced by infusion of dexamethasone or adrenocorticotrophin to the fetus.

Premature delivery was induced by intrafetal infusion of dexamethasone or (1-24)ACTH, starting between days 124 and 129 of pregnancy in twelve ewes carrying intact (n = 7) or hypophysectomized (n = 5) single fetuses. Concentrations of ovine placental lactogen (oPL) in maternal plasma were measured by specific radioimmunoassay before and during premature delivery. There was no significant change in oPL concentrations before delivery in ewes carrying either intact or hypophysectomized fetuses. The results suggest that a prepartum decline in oPL is not an essential prerequisite for delivery, and indicate that fetal glucocorticoids are not directly responsible for the prepartum fall in oPL concentrations observed at spontaneous delivery.

Animals↗
PubMed1983

Concentrations of prolactin in the plasma of fetal sheep and in amniotic fluid in late gestation and during dexamethasone-induced parturition.

The concentration of prolactin in samples of fetal plasma and amniotic fluid collected from sheep with indwelling catheters has been measured by radioimmunoassay. There was considerable variation between animals in the concentration of prolactin in fetal plasma which ranged from less than 2 micrograms/l to greater than 50 micrograms/l. In five out of eight fetuses which were sampled at intervals throughout the last 30 days of pregnancy, there was an increase in the concentration of prolactin in the plasma before parturition. The concentration of prolactin in amniotic fluid was consistently low (approximately 1 microgram/l). Induction of premature parturition by intrafetal infusion of dexamethasone was accompanied by an increase in the concentration of prolactin in only one of three fetuses infused. These results indicated that prolactin is present in fetal plasma but that an increase in prolactin in fetal plasma before the onset of parturition does not always occur. The low concentration of prolactin in amniotic fluid contrasts with the high concentrations of this hormone found in the amniotic fluid of the primate.

Amniotic Fluid↗
PubMed1983

The regulation of ovine placental lactogen the role of the fetal hypothalamic-pituitary axis.

The possible rôle of the fetal hypothalamic-pituitary axis in regulating the secretion of ovine placental lactogen (oPL) was investigated in chronically-catheterised ewes and fetuses in late pregnancy. Intravascular administration of agents to fetuses that significantly increased fetal prolactin concentrations (chlorpromazine 6.25 mg;thyrotrophin releasing hormone, 10 micrograms), significantly reduced fetal prolactin concentrations (bromocriptine, 0.033 mg/h), or significantly reduced fetal growth hormone (GH) concentrations (somatostatin, 2.5 micrograms/min), had no effect on maternal or fetal oPL concentrations. Mean fetal levels of prolactin or GH in late gestation could not be correlated with oPL concentrations, although fetal hypophysectomy prevented the normal prepartum fall in oPL concentrations.

Animals↗
PubMed1983

Effect of intrauterine death and fetectomy on ovine placental lactogen production.

Concentrations of ovine placental lactogen (oPL) were measured in the peripheral plasma of six ewes after the removal of fetuses (in four ewes) or after the intrauterine death of one of twin fetuses (in two ewes). Concentrations of oPL decreased after fetectomy or intrauterine fetal death, indicating that a living fetus is essential to the sustained secretion of oPL.

Animals↗
PubMed1982

Ultrastructural evidence for steroid-hormone production in the adrenal of the marsupial Isoodon macrourus, at birth.

To determine whether the adrenal gland of the bandicoot is actively producing steroid hormones at birth, the cellular structure was examined by electron microscopy, and the concentration of cortisol in the gland was determined by radioimmunoassay. Two distinct cell populations were seen in the adrenal gland. One group of cells possessed dark staining granules, normally observed in catecholamine-secreting cells, and the second group contained large amounts of smooth endoplasmic reticulum and mitochondria with tubulo-vesicular cristae. Both features are characteristic of steroid-secreting cells. A concentration of 0.094 ng of cortisol per adrenal was determined by pooling glands from nine individual newborn bandicoots. This evidence of cortisol secretion from the bandicoot adrenal at birth indicates that, as in many eutherians, the marsupial adrenal may play an important role in determining the length of gestation.

Adrenal Glands↗
PubMed1982

Effects of hydroxysteroid dehydrogenase inhibitors on in-vitro and in-vivo steroidogenesis in the ovine adrenal gland.

The effectiveness of trilostane and azastene as inhibitors of adrenal steroidogenesis was compared by in-vitro and in-vivo methods. A radioimmunoassay was developed for the measurement of cortisol in ovine plasma, incubation medium and tissue extract using a specific antiserum raised against cortisol 21-acetate,3-carboxymethyloxime:bovine serum albumin. Trilostane (20 mumol/l) decreased cortisol synthesis and release both in unstimulated and in ACTH-stimulated adrenal tissues in vitro. The same concentration of azastene had a lesser effect on unstimulated adrenals and was completely ineffective in blocking the stimulatory action of ACTH. In vivo, trilostane suppressed adrenal steroidogenesis in pregnant and cyclic ewes but the suppression in pregnant ewes was over a longer period, and after lower doses. It is concluded that trilostane had an inhibitory effect on ovine adrenal steroidogenesis both in vitro and in vivo.

Abortifacient Agents↗
PubMed1981

Prolactin and LH release in response to LH-RH and TRH in ewes during dioestrus, pregnancy and post partum.

With advancing pregnancy in the ewe there was a marked decline in plasma LH concentrations and pituitary LH-RH responsiveness (integrated LH release) and a marked increase in plasma prolactin values and pituitary TRH responsiveness (integrated prolactin release). In lactating ewes plasma LH levels and pituitary LH-RH responsiveness had returned to values found in the luteal phase of the normal cycle by 21 days post partum, whereas at 42 days post partum prolactin levels were still high. No interaction between TRH and LH-RH on prolactin and LH release in dioestrous ewes was detected. In non-pregnant ewes plasma prolactin levels were significantly higher in June than in January but TRH responsiveness was similar. It is concluded that, in sheep, pituitary LH secretion recovers more rapidly from the chronic negative feedback effect of oestrogens and progesterone in pregnancy than prolactin secretion recovers from the chronic positive feedback effects of oestrogens. This finding may be a contributory factor in the resistance to resumption of breeding activity.

Animals↗
PubMed1980

Review: The mechanism of action of danazol, a novel steroid derivative.

Danazol is being increasingly used for the treatment of a wide range of disorders, many of which appear to bear little relation to the condition for which the drug was originally marketed--endometriosis. It has been claimed that this drug acts by means of its antigonadotrophic effects on the pituitary; however, a review of the literature reveals that its efficacy in suppressing normal endometrial growth and in causing atrophy of deposits of endometrium cannot be explained solely on this basis. Recent information indicates that, besides acting at the pituitary level, a major mechanism of action may be by a direct inhibitory effect on target tissue. It is sugggested that such a mechanism would more readily account for the diverse effects of this drug in the treatment of many disorders, all of which appear to be associated with an imbalanced sensitivity of target organs to steroid hormones. A greater understanding of its mechanism of action could lead to an even wider application of this novel drug.

Danazol↗