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Biomedical subjects

R B Heap

Publications and source records attributed to R B Heap.

At least 91 records · Page 5Linked to original sources
PubMed1983

An improved model of the distribution and metabolism of progesterone and 20 alpha-dihydroprogesterone in sheep.

When [3H]progesterone is infused intravenously into ewes, blood 20 alpha-dihydroprogesterone (20 alpha-diHP) becomes labelled and the changes in [3H]20 alpha-diHP activity with time are clearly related to that of [3H]progesterone. Concentrations of 20 alpha-diHP in blood have now been estimated for these experiments. During the infusion, the specific radioactivity of 20 alpha-diHP at steady state was only 53% of the specific radioactivity of progesterone, indicating that 20 alpha-diHP was produced other than by C-20 reduction of secreted progesterone. The change in blood concentration of 20 alpha-diHP during pregnancy in ewes suggests that the placenta is its source. [3H]20 alpha-dihydroprogesterone was infused into pregnant ewes and the specific radioactivity of 20 alpha-diHP measured during and after infusion. Together with information from earlier experiments when [3H]progesterone was infused, there is now sufficient data to estimate, without constraint, the parameters of a four-pool model describing the distribution and metabolism of progesterone and 20 alpha-dyhydro-progesterone in sheep.

20-alpha-Dihydroprogesterone↗
PubMed1983

Transport of free and conjugated steroids from the boar testis in lymph, venous blood and rete testis fluid.

In 12 anaesthetized boars the concentrations of oestrone sulphate and dehydroepiandrosterone sulphate (DHAS) were 15- to 35-fold higher in lymph collected from a vessel in the spermatic cord than in testicular venous blood plasma from a vein in the spermatic cord. The concentrations of testosterone, total unconjugated oestrogens and dehydroepiandrosterone (DHA) were about twofold higher in lymph. The concentrations of all steroids studied were higher in testicular venous blood plasma than in arterial blood plasma (testosterone about sixfold; total unconjugated oestrogens about fourfold; oestrone sulphate about threefold; DHA and DHAS about twofold), but the concentrations of testosterone, total unconjugated oestrogens and oestrone sulphate in rete testis fluid were comparable to those in arterial blood plasma. Lymph flow from the pig testis was about 7% of plasma flow so that about 80% of the oestrone sulphate and DHAS produced by the testis leaves the organ in the lymph; the comparable values for testosterone, total unconjugated oestrogen and DHA were about 20%. In the 90-min period following an injection of human chorionic gonadotrophin there were substantial increases in the concentration of testosterone and smaller increases in the other steroids in arterial and spermatic venous blood plasma and in testicular lymph, but not in rete testis fluid; there were also small increases in lymph flow, but no change in blood flow.

Androgens↗
PubMed1983

Oestrogen metabolism in the endometrium, corpus luteum and ovarian residual tissue of the rabbit.

Reproductive tissues (uterine endometrium, corpus luteum and ovarian residual tissues) from pregnant and pseudopregnant rabbits were incubated with equimolar concentrations of [3H]oestrone and [3H]oestrone sulphate (0.375 pmol) to monitor the changes in oestrogen metabolism during the early stages of pregnancy (days 0, and 3-8 post coitum) and to investigate the embyonic effect upon maternal oestrogen metabolism. Oestradiol-17 beta was the major metabolite formed from oestrone and sulphoconjugation occurred in all tissues studied. Oestrone sulphate was converted primarily to oestradiol-17 beta-3-monosulphate. Endometrial 17 beta-oxidoreductase significantly decreased and sulphotransferase increased in activity during the preimplantation period, but no differences were noted between gravid and non-gravid horns in unilaterally pregnant animals, nor between pregnant or pseudopregnant animals. Significant decreases occurred in 17 beta-oxidoreductase and sulphotransferase activity in luteal tissue, but these were more than offset by increases in tissue weight. No differences in the activities in luteal tissues were detected between pregnant or pseudopregnant animals, nor between ovarian tissue adjacent to gravid or non-gravid uterine horns. The results show that significant changes occur in oestrogen metabolism in the rabbit endometrium and corpus luteum within 8 days after ovulation, and that these changes result from maternal factors expressed systemically rather than by the effects of the developing conceptus expressed locally.

Animals↗
PubMed1983

Influence of certain steroids on lymphocyte transformation in sheep and goats studied in vitro.

The effect of various steroids on lymphocyte transformation was tested with peripheral blood lymphocytes (PBL) from sheep and goats. Transformation was induced with phytohaemagglutinin, pokeweed mitogen and Concanavalin A, and by allogeneic lymphocytes (mixed lymphocyte culture). Progestagens, androgens and corticosteroids inhibited mitogen-induced transformation of lymphocytes from both species. With sheep PBL, progestagens and androgens inhibited transformation at high concentrations. Progesterone and its less active metabolites 5 alpha-pregnanedione and 20 alpha-dihydro-progesterone were equally inhibitory. Corticosteroids were more effective than other steroids at concentrations of less than 1 mumol/l. Oestrogens had relatively little effect with the exception of diethylstilboestrol which markedly enhanced sheep PBL responses to mitogen. Structural comparisons suggested that the most suppressive C-19 and C-21 steroids possessed 4-en-3-one configuration in ring A, and that inhibitory activity was enhanced by C-17 alpha substitution as in 17 alpha-hydroxyprogesterone. The steroid effects on PBL were largely unaffected by the reproductive status of the donor, were exerted during the early pre-replicative phase rather than at the time of new DNA synthesis, and were not attributable to cytoxicity nor to changes in intracellular thymidine pools. An exception was found with the non-steroidal oestrogen, diethylstilboestrol, which enhanced the response to mitogen-treated cultures of sheep lymphocytes at both early and late phases of the cell cycle. It is concluded that several naturally occurring steroids affect the responsiveness of PBL to mitogenic stimuli, and that progesterone and/or certain of its metabolites may be effective in vivo when present at the high concentrations found in the utero-ovarian lymphatic network draining the gravid uterus or at the trophoblast-maternal interface in the sheep and goat.

Adrenal Cortex Hormones↗
PubMed1983

Mammary uptake and metabolism of progesterone in goats and its effect on milk progesterone concentrations during the oestrous cycle and early pregnancy.

Following the observation that the concentration of progesterone in goats' milk differs appreciably according to the specificity of the antiserum used in a non-extraction (direct) radioimmunoassay, experiments were carried out to find an explanation for these results. Milk and plasma samples were collected during the oestrous cycle and during an equivalent period of pregnancy after a fertile mating. Samples were analyzed by a direct radioimmunoassay using two antisera, 18/3 which is highly specific for progesterone and 465/6 which is less specific, and by radioimmunoassay of fractions isolated by thin-layer chromatography (TLC). Values obtained for milk and plasma samples collected during the oestrous cycle and early pregnancy were similar, except that values for milk samples measured with antiserum 465/6 were higher in pregnancy compared to those obtained during the oestrous cycle. Values obtained for milk and plasma with antiserum 465/6 were significantly higher than those obtained with 18/3 (P less than 0.001). After TLC this difference was found to be due principally to the presence of compound(s) with chromatographic properties identical to 5-pregnanedione(s). A comparison of the concentration measured in arterial and mammary venous plasma and in milk showed that about 25% of progesterone (5.7 nmol/min) was extracted by the mammary gland, and that substantial amounts of immunoreactive metabolites of progesterone are secreted into milk with only small quantities being transferred into mammary vein plasma.

Animals↗
PubMed1983

Sources of progesterone during gestation in Barbary sheep (Ammotragus lervia).

Concentrations of progesterone in arterial and ovarian, uterine and jugular venous plasma were determined in four Barbary sheep at various stages of pregnancy. The results, together with ovarian histology, show that the corpus luteum regresses before term in Barbary sheep, as in most breeds of domestic ewes. Uterine synthesis of progesterone was demonstrated in late pregnancy in two animals in which uterine venous levels of progesterone were increased two- to fourfold above arterial concentrations. The placenta contained 3 beta-hydroxysteroid dehydrogenase. Barbary sheep (diploid chromosome number, 2N = 58) therefore resemble the domestic sheep (2N = 54) rather than the goat (2N = 60) from the point of view of the source of the progesterone required for maintenance of pregnancy.

Animals↗
PubMed1982

A rapid direct radioimmunoassay for the measurement of oestrone sulphate in the milk of dairy cows and its use in pregnancy diagnosis.

A radioimmunoassay for oestrone sulphate in unextracted samples of milk has been developed. The assay was validated by comparison with a method involving hydrolysis and extraction. The direct assay was used to measure oestrone sulphate in milk samples taken at weekly intervals throughout pregnancy in a commercial dairy herd. Concentrations of oestrone sulphate increased approximately 100 days after insemination and were maintained throughout the remainder of pregnancy in the range of 1.85-3.70 nmol/l.

Animals↗
PubMed1982

Studies on oestrogen synthesis by the preimplantation equine conceptus.

Aromatase activity measured by the incorporation of [3H]androstenedione into unconjugated and conjugated oestrogens was detectable in the equine conceptus during early pregnancy. Activity was substantially higher in yolk sac compared to allantochorion between Days 20 and 52 after ovulation. Oestrone sulphate concentrations in yolk-sac fluid measured by radioimmunoassay increased markedly to reach values of about 3 micrograms/ml at Day 36, approximately 10-fold higher than those in allantoic fluid. Extra-embryonic membranes in a 28-day conceptus all contained aromatase (chorionic girdle greater than trilaminar omphalopleure greater than bilaminar omphalopleure greater than allantochorion), implying that the enzyme complex was present in trophoblast and/or endoderm rather than mesoderm. Aromatase activity in chorionic girdle cells was low before their migration into the endometrium. Endometrial tissue contained substantial sulphotransferase and glucuronidase activity. The ability of the preimplantation equine conceptus to synthesize oestrogens was strikingly similar to that found previously in the pig; in both species the allantochorionic placenta is non-invasive.

Allantoin↗
PubMed1981

Autoradiographic evidence for migration and fusion of cells in the sheep placenta: resolution of a problem in placental classification.

The location of the fetomaternal junction in the placenta is important with respect to structural classification and the identification of any possible barrier to maternal immunorejection. Structural classification of the sheep placenta remains controversial on account of the uncertain origin of the syncytial layer. In this study [3H]thymidine was injected into the fetus and placentomes were removed between 4h and 21 days afterwards. Autoradiography showed that the syncytium is derived predominantly from the migration of fetal binucleate cells and not from the maternal uterine epithelium as most recent reports have suggested. In this respect the origin of the syncytium in the sheep placenta is similar to that reported in certain other eutherian mammals. The finding that cells originating from the fetal allograft survive after migration through the microvillous junction poses questions as to the mechanism by which the syncytial layer resists maternal immune rejection throughout gestation.

Animals↗
PubMed1981

Effects of pregnancy on the febrile responses in sheep.

Pyrogens were injected into unshorn pregnant and non-pregnant Soay and Clun Forest sheep and the effects on rectal temperature and thermoregulatory mechanisms monitored. Plasma concentrations of unconjugated oestrogens, progesterone and cortisol were measured in the sheep tested in late pregnancy. The effect of pyrogens was also examined in ovariectomized ewes treated with oestrogen and with oestrogen plus progesterone. In contrast to reports of work on shorn sheep all sheep developed a fever even when close to term but the increase in peripheral vasomotor tone normally induced by pyrogens was attenuated in the pregnant Clun Forest ewes. The hormone-treated ovariectomized animals developed normal fevers and provided little indication of a possible relation between peripheral levels of ovarian steroids and the degree of fever. The question of whether an endogenous antipyretic substance is present in pregnant sheep is discussed.

Animals↗
PubMed1981

Protein, prostaglandin and steroid synthesis in caruncular and intercaruncular endometrium of sheep before implantation.

The effect of the presence of a preimplantation embryo on protein concentration, rate of protein synthesis, beta-glucuronidase and acid phosphatase activities, steroid metabolism and prostaglandin F production in caruncular and intercaruncular tissue have been studied for sheep at Day 15 of pregnancy. The rate of protein synthesis in both tissues was greater in pregnant than in non-pregnant animals, although the difference was only significant in caruncular endometrium. The effect in caruncular tissue was mimicked in ovariectomized animals treated with oestradiol. Localized changes in the caruncular tissue were observed in respect of PGF with an increased tissue concentration, an enhanced basal release when the tissue was incubated in the presence of indomethacin, and a decreased net production. Maximum production of PGF in the 2 tissues was unaffected by the presence of an embryo but it was enhanced by oestradiol or progesterone treatment in intercaruncular tissue of ovariectomized ewes. beta-Glucuronidase and acid phosphatase activities and steroid metabolism were unaffected by pregnancy. However, in ovariectomized animals oestradiol treatment stimulated beta-glucuronidase activity in endometrium and myometrium. Progesterone treatment stimulated acid phosphatase activity in the intercaruncular endometrium. The results show that amongst several endometrial constituents investigated relatively few changes were detected by Day 15 post coitum, one day before definitive attachment. Those changes that did occur were associated with the dynamics of PGF production and the rate of protein synthesis, and were consistent with the production of a PGF binding component in caruncular endometrium which may be concerned with the protection of luteal function by redirection of uterine PGF production. Canonical variate analysis revealed that changes on Day 15 of pregnancy were mimicked most closely in caruncular tissue by treatment of ovariectomized ewes with oestradiol and progesterone, and in intercaruncular tissue by oestradiol treatment only.

Acid Phosphatase↗
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↗