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Biomedical subjects

R B Heap

Publications and source records attributed to R B Heap.

At least 73 records · Page 4Linked to original sources
PubMed1986

Residual milk in Friesland sheep and the galactopoietic effect associated with oxytocin treatment.

Mature lactating Friesland ewes had a mean lactation yield of 293 +/- 26 kg during a lactation period of 35 +/- 2 weeks giving an average daily milk yield of 1.2 kg/d. Ewes were injected intravenously after normal milking with either saline (sham) or oxytocin and then remilked to determine the volume of residual (alveolar) milk. After a long milking interval of 16 h oxytocin treatment gave a significantly greater total daily milk yield than the sham treatment (oxytocin minus saline, morning milking, 0.199 +/- 0.038 kg, mean +/- s.e.m., P less than 0.01) Oxytocin had a small significant reverse effect after a short milking interval of 8 h (afternoon milking, -0.065 +/- 0.022 kg, P less than 0.05). The average increase in total daily yield over four stages of lactation was 0.133 +/- 0.029 kg (P less than 0.01), or 11% of the average daily milk yield. The galactopoietic effect of oxytocin was associated with the efficient removal of residual (alveolar) milk. Residual milk accounted for 7.4 and 27.2% of the total daily milk yield in ewes treated with saline or oxytocin respectively. Residual milk expressed as a proportion of daily total milk yield remained steady in ewes studied between April and July, but declined in September when yields were less than 1 kg/d.

Animals↗
PubMed1986

The effect of day length on the duration of pregnancy and the onset of parturition in the rat.

Rats mated under normal lighting conditions of a 24 h day were transferred to a sound-proof room with period lengths (T) of 24 h (12 h light and 12 h dark, 12L:12D), or 22 h (11L:11D). During the first 15 d of pregnancy the rats were kept together in a large enclosure and the locomotor activity of the group was recorded. From day 15 they were kept separately, in cages, and from day 21 the number of litters born was noted every 3 h. On 12L:12D, rats displayed well defined periods of activity which were closely related to photoperiod. Mean activity was greatest in the dark, and overall activity declined after day 13 of gestation. On 11L:11D, coupling of locomotor activity to the dark phase was retained initially, but was not sustained throughout the period of study. Activity in the light was comparable to that in the dark at the time when the light:dark cycles of 11L:11D became reversed relative to those of 12L:12D. Rats on a 24 h day had a peak time of delivery at 519 h after mating (21.6 cycles of 12L:12D) and those on a 22 h day at 527 h (24.0 cycles of 11L:11D; difference, P less than 0.002). The 11L:11D cycle therefore increased rather than decreased the duration of pregnancy, implying that elapsed time rather than the number of light:dark cycles experienced has the greater influence on the length of gestation. Of the animals on a 24 h day 76% had their litters in the light phase of the cycle, whereas only 36% of those on a 22 h day gave birth in the light (P less than 0.02).

Activity Cycles↗
PubMed1986

Heterologous anti-progesterone monoclonal antibody arrests early embryonic development and implantation in the ferret (Mustela putorius).

Early embryo development and implantation were arrested in ferrets passively immunized with a mouse monoclonal anti-progesterone antibody injected intraperitoneally at 72 and 96 h post coitum (p.c.) or at 72 h p.c. only. In control ferrets injected with mouse serum or 0.9% NaCl, implantation sites were found in all mated females; autopsies were carried out at Day 14 p.c. A total of 34 unimplanted embryos were recovered from the reproductive tract of antibody-treated ferrets and none of these had progressed to the blastocyst stage. When ferrets were treated with antibody at 72 h p.c. and autopsies were carried out at Day 6 p.c., only 1 of 29 embryos recovered had progressed beyond the 4-cell stage in 4 females. In 4 control animals most embryos recovered at Day 6 were at the morula (32%) or blastocyst (28%) stage. Embryos from ferrets treated with antibody were therefore developmentally arrested when recovered 72 h after antibody administration. Plasma progesterone concentrations were approximately 6-fold higher in antibody-treated ferrets with unimplanted embryos (711 +/- 132 nmol/l; 223 ng/ml) compared with control pregnant females (102 +/- 4 nmol/l; 32 ng/ml) at Day 14 p.c. The results are consistent with the hypothesis that the normal course of pregnancy is arrested as a result of antibody binding of progesterone in the circulation, presumably causing a decrease in the amount of progesterone available to target cell receptors, and that heterologous anti-progesterone antibody blocks normal cleavage and embryonic development at an early stage before cavitation.

Animals↗
PubMed1986

Control of binucleate cell migration in the placenta of sheep and goats.

In the ruminant placenta 15-20% of the trophectodermal epithelium consists of granulated binucleate cells (BNC). In the sheep the granules contain ovine placental lactogen (oPL). These cells migrate from the trophectoderm to form fetomaternal hybrid tissue from implantation to term. The number of BNC, their percentage migration and the potential secretory activity of the syncytium they form were estimated by semiquantitative transmission electron-microscopical techniques after several surgical techniques and hormone or drug infusions. BNC numbers decrease normally just before parturition, and this fall could be eliminated by fetal hypophysectomy or induced early by administration of tetracosactrin to intact or hypophysectomized fetuses. If only one twin was treated with tetracosactrin the placenta of the untreated twin did not show the fall in BNC numbers found in the other unless it died in utero some time before sampling. This indicates fetal control of BNC number and migration. However, fetal catheterization, hypophysectomy, stalk section, adrenalectomy, infusion of mouse epidermal growth factor or bromocriptine had little or no effect on binucleate cell numbers or migration percentages. Maternal carunclectomy, ovariectomy, or epostane or bromocriptine administration also had no consistent significant effect. Previous reports of degeneration of BNC structure plus a decrease in their number (with bromocriptine) or an increase in migration frequency (after adrenalectomy or stalk section) have not been confirmed by this study. The BNC migration delivers the oPL-containing BNC granules close to the maternal circulation but the variation in migration seems only loosely correlated with the reported maternal oPL concentrations. The results indicate that BNC migration is independent of the hormonal milieu, but that BNC production is greatly modified by the hormonal changes just before parturition, with cortisol production by the fetus a possible primary cause.

Adrenalectomy↗
PubMed1986

Anti-fertility effect of passive immunization against progesterone is influenced by genotype.

The anti-fertility effect of a monoclonal progesterone antibody injected i.p. 32 h after mating is influenced by genotype since a single dose of 5.7 nmol immunoglobulin G successfully blocked the establishment of pregnancy in BALB/c but not in F1 hybrid mice (CBA male X BALB/c female). Progesterone concentrations in circulation were significantly higher at days 3 and 4 after mating in F1 females compared with those of the BALB/c stock. Moreover, the pattern of mitotic activity in the endometrium after passive immunization differed between the two genotypes. In treated BALB/c mice there was no increase in mitotic activity in stromal cells at days 3, 4 and 5 after mating (in contrast to BALB/c control females in which the number of stromal mitoses increased sharply). In F1 females there was a transient effect of antibody at day 3 (no increase in stromal mitoses but enhanced mitotic activity in the glandular epithelium compared with F1 control females), and subsequently a normal increase in mitotic divisions in stromal cells. The hypothesis is proposed that passive immunization against progesterone at 32 h after mating will only block the establishment of pregnancy in genotypes in which there is a gradual, rather than a steep rise in circulating progesterone concentrations during the preimplantation period. In F1 mice, high concentrations of circulating progesterone at days 3 and 4 of pregnancy apparently over-ride the effect of antibody and facilitate the normal development of stromal mitotic activity associated with the onset of implantation.

Animals↗
PubMed1986

Kinetics of transfer of 125I-labelled epidermal growth factor from blood into mammary secretions of goats.

125I-Labelled mouse epidermal growth factor (125I-EGF) was transferred intact and undegraded from circulating blood into milk in conscious lactating goats. Greater than 90% of the total radioactivity present in milk from the infused gland was in the aqueous phase and more than 72% was acid-precipitable. This radiolabelled material co-eluted with authentic EGF through gel filtration and was immunoprecipitable by a specific rabbit anti-mouse EGF immunoglobulin. Mammary uptake of 125I-EGF infused into mammary arterial blood (close-arterial infusion) for 1 h varied from 20 to 83% at different stages of the reproductive cycle. Only 0.5-2.9% of the infused 125I-EGF was transferred into milk during the first 3 h after the start of the infusion, which represents 0.7-6.3% of mammary uptake of EGF. The kinetics of transfer of 125I-EGF were followed in two lactating goats. Radioactivity reached peak levels in milk about 120 min after the start of a 1 h close-arterial infusion into the mammary gland, with an initial lag of about 30 min when little transfer occurred. Transfer was slower in two non-lactating goats with maximal levels of activity in milk being reached after about 180 min. The results are consistent with a transcellular transfer, whereby the factor is bound to receptors on the baso-lateral membrane, internalized by epithelial cells and subsequently secreted across the apical membrane into the alveolar lumen. The low level of degraded labelled EGF in milk (and mammary vein blood) suggests a modification of the normal pathway of EGF degradation such that the delivery of internalized factor to lysosomes is avoided.

Animals↗
PubMed1986

Anti-idiotypic sera against monoclonal anti-progesterone antibodies: production in rabbits and rats and characterization of specificity.

Antisera were raised in rabbits and rats against three mouse monoclonal anti-progesterone IgG1 antibodies. Anti-idiotypic antibodies were isolated from rabbit sera by successive passage over immunoadsorbent columns of normal mouse Ig and the specific immunizing monoclonal, with elution from the latter. Radioimmunoassays for anti-idiotype and free idiotype were established, enabling detection of idiotype in sera of mice immunized with progesterone-BSA conjugate. Binding of rabbit anti-idiotype to anti-progesterone monoclonals was partially inhibitable by free progesterone-hemisuccinate or progesterone-ovalbumin conjugate. While showing considerable specificity for their respective inducing monoclonals, the anti-idiotypes also cross-reacted in varying degrees with the other anti-progesterone monoclonals, demonstrating the presence of IdI and IdX determinants. The patterns of cross-reactivity showed some correlation with the relative isoelectric points and combining-site specificities of the anti-progesterones. The specificities of rat and rabbit anti-idiotypes were similar, but not identical.

Animals↗
PubMed1986

Mechanisms of transfer of steroid hormones and growth factors into milk.

In this paper we examine the ability of the mammary gland to remove from circulating blood three compounds which differ in their physico-chemical and structural properties. Mammary extraction of progesterone, oestrone sulphate and epidermal growth factor (EGF) is similar at peak lactation in goats, but the proportion of labelled infusate that is transferred into milk is greater for oestrone sulphate and EGF than progesterone which is rapidly metabolised by mammary tissue. The kinetics of transfer of progesterone, oestrone sulphate and EGF from blood into milk show that transcellular processes are involved, and on the basis of earlier hypotheses and new information reported here the results indicate the probable importance of simple and facilitated diffusion pathways for progesterone and oestrone sulphate, and secretory mechanisms for oestrone sulphate and EGF. Although evidence is lacking for a direct effect of hormones in milk on mammary function, their concentration in milk may reflect changes in local regulation of mammary secretion. Considerable practical value is attached to the immunodiagnostic use of milk hormone concentrations to determine ovarian and placental endocrine activity during pregnancy in domestic ruminants.

Animals↗
PubMed1986

Secretion of oestrone sulphate into milk.

A Golgi apparatus-enriched fraction obtained from lactating rat mammary glands has been used to investigate the binding transport of oestrone sulphate using radio-labelled ligand. The fraction showed good galactosyl transferase activity and was substantially intact when assayed for lactose synthase activity. Binding sites for the hormone on the Golgi membrane were demonstrated and at 4 degrees C binding was a linear function of concentration over the range 0.2 mol 1(-1) to 25 mmol 1(-1). The hormone was readily displaced by high concentrations of oestrone sulphate but not by oestrone, 17-beta-oestradiol or progesterone. Lysis of the vesicle prior to binding of oestrone sulphate allowed additional hormone to bind but only when lysis conditions were mild. Nevertheless, the hormone could be readily displaced by simple dilution of the reaction medium suggesting that binding was to the cytosolic surface of the membrane. No evidence of the transport of the hormone into the lumen of the vesicle was obtained.

Animals↗
PubMed1985

Prostaglandin F-2 alpha is transferred from the uterus to the ovary in the sheep by lymphatic and blood vascular pathways.

[3H]Prostaglandin F-2 alpha (PGF-2 alpha) was infused into a uterine lymphatic vessel or a uterine vein for up to 1 h, or injected into the uterine lumen of anaesthetized non-pregnant sheep 7-15 days after oestrus. After an intraluminal injection, labelled PGF-2 alpha was recovered in uterine lymph and peak radioactivity was reached 50 min after injection. [3H]PGF-2 alpha infused at a constant rate into a uterine lymphatic vessel resulted in a maximum concentration of radioactivity in plasma which was 5.6- and 1.7-fold higher in the adjacent utero-ovarian and ovarian vein, respectively, than in carotid arterial plasma. Estimation of the amount of infusate transferred from a lymphatic into ovarian venous blood gave a value (0.4%) similar to that for transfer from a uterine vein (0.3%). Evidence for local transfer was substantiated by the presence of significantly higher concentrations of 3H-labelled compounds in the ovary and corpus luteum adjacent to the site of intra-lymphatic infusion compared with those in the opposite organs. The concentrations in the adjacent ovary and corpus luteum were significantly greater when an intra-lymphatic rather than intra-uterine vein infusion was adopted. The results show that [3H]PGF-2 alpha is transferred locally from uterine lymphatic vessels into the adjacent ovary, corpus luteum and ovarian vein.

Animals↗
PubMed1985

Passive immunization against progesterone inhibits endometrial sensitization in pseudopregnant mice and has antifertility effects in pregnant mice which are reversible by steroid treatment.

Pregnant mice were injected 32 h post coitum (p.c.) with a monoclonal antibody against progesterone (5.7 or 9.5 nmol immunoglobulin G (IgG)) or 0.9% (w/v) NaCl (controls). Progesterone was injected starting on day 2, 3, 4 or 5 p.c. Progesterone reversed the antifertility effect of the lower dose of antibody when replacement began on day 2, 3 or 4, though the number of implantation sites was reduced when treatment started on day 3 or 4. By day 5 only one of six treated animals remained pregnant, showing that antibody action was reversible only up to day 4. At the higher dose of antibody, exogenous nidatory oestrogen was also required. Pseudopregnant mice were injected 32 h p.c. with this antibody (5.7 nmol IgG) or 0.9% NaCl (controls). At 16.00 h on day 4 p.c., oil was injected into the lumen of one uterine horn and the magnitude of the decidual cell reaction was assessed 72 h later. Injected horns of antibody-treated females did not respond to intraluminal oil, whereas those of control mice increased fivefold in weight. Steroid treatment after the induction stimulus did not promote decidual growth, indicating that passive immunization reduced endometrial sensitivity. The results show that in the event that antibody fails to arrest the development of all embryos, the absence of endometrial sensitization will preclude the initiation of implantation, unless progesterone is given within 48 h of antibody treatment.

Animals↗
PubMed1984

Structural requirements for steroid inhibition of sheep lymphocyte mitogenesis in vitro.

The inhibitory effects of different steroids and related compounds on sheep peripheral blood lymphocytes (PBL) during exposure to the mitogen, phytohemagglutinin (PHA), have been measured by the reduction of [3H]thymidine incorporation into DNA. Dose-response curves showed that a maximum (or near maximum effect) was achieved at a steroid concentration of 12.5 microM. At this dose 19 of 41 compounds significantly reduced thymidine incorporation by activated PBL (P less than 0.01 to P less than 0.001). The greatest reduction was observed with 17-hydroxyprogesterone (-59%, i.e. reduced by 59% compared with vehicle control, 100%) greater than androstenedione greater than epitestosterone greater than estradiol-3-methyl ether greater than 20 alpha-dihydroprogesterone greater than medroxyprogesterone acetate greater than 5 beta-pregnane-3,20-dione greater than 5 alpha-pregnane-3,20-dione (-24%). Among the steroids which showed the greatest inhibitory effect, 6 had a 4-en-3-one group in ring A, 4 had a saturated ring A (pregnane or androstane) and one had a 3-methyl ether group and a phenolic ring A. The wide range of structures represented by these inhibitory steroids suggests that inhibition of lymphocyte mitogenesis involves more than one mechanism.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Action of anti-progesterone monoclonal antibody in blocking pregnancy after postcoital administration in mice.

Anti-progesterone monoclonal antibody injected intraperitoneally as a single dose 32 h post coitum completely blocked pregnancy in BALB/c and CBA nulliparous mice. The dose required was greater in CBA than in BALB/c females, but in both strains no implantation sites were detectable at autopsy on day 10 after mating. The action of the antibody in BALB/c females was associated with a failure to initiate an implantation response as indicated by the Pontamine Blue reaction. The most pronounced effect, however, was an arrest of embryonic development at a stage prior to cavitation. Plasma progesterone concentration in blood taken by cardiac puncture was greatly increased after treatment, by virtue of high-affinity binding by antibody in circulation. The results show that passive immunization against progesterone shortly after mating interferes with early hormone-dependent steps which are essential for normal embryonic development.

Animals↗
PubMed1984

Transport of oestrone sulphate by the mammary gland in the goat.

During pregnancy in goats the concentration of endogenous oestrone sulphate in milk increased more than twofold, and that in arterial and mammary venous plasma 10- and 20-fold respectively. The concentration in milk was higher than that in arterial plasma, particularly in lactating goats during mid-gestation. This was partly related to mammary production of oestrone sulphate (or of a closely related steroid which cross-reacted in the radioimmunoassay) since in tracer infusion studies the specific activity of oestrone sulphate in milk was significantly lower than that in arterial or mammary venous plasma. It was also related to the existence of a mechanism within the gland which concentrates oestrone sulphate in milk since when infused close-arterially into the mammary gland of a non-pregnant goat with undetectable levels of the endogenous compound in the circulation, a concentration ratio of 7.4:1.0 was reached for oestrone sulphate in milk:arterial plasma. Tracer kinetic studies showed that mammary extraction of [3H]oestrone sulphate was variable (up to 41.3 +/- 30.6%, mean +/- S.E.M.). During intravenous or close-arterial infusion, radioactivity in arterial and mammary venous plasma at steady state was mainly in the form of [3H]oestrone sulphate (range, 64 +/- 10.6 to 80.2 +/- 5.9% of total radioactivity in plasma). The remainder was in the form of compounds chromatographically similar to oestradiol-17 beta-3-monosulphate, oestradiol-17 alpha-3-monosulphate and unconjugated oestrogens. The distribution of radioactivity between these different steriods was similar in arterial mammary venous plasma indicating a low level of selective mammary metabolism or extraction. The amount of labelled oestrone sulphate transferred into milk was low, and it was significantly less in pregnant (range, 0.11 +/- 0.07 to 0.27 +/- 0.16% of total infusate) than in non-pregnant animals (3.23 +/- 0.50%). Studies of the rate of transfer of [3H]oestrone sulphate from blood to milk indicated the presence of a transcellular route with peak activity in milk occurring about 110 min after the start of the infusion.

Animals↗
PubMed1984

Ovarian steroid metabolism and oestrogens in the corpus luteum of the tammar wallaby.

Ovaries were obtained from tammar wallabies at various stages of the reproductive cycle to examine the occurrence of oestrogens in corpora lutea, and the synthesis and metabolism of steroids in the corpus luteum and ovarian cortical and interstitial tissues. Corpora lutea contained oestradiol-17 beta and oestrone during embryonic diapause and at all stages of pregnancy studied after blastocyst activation. Aryl sulphatase, 3 beta-hydroxysteroid dehydrogenase and 17 beta-oxidoreductase were shown to be present in luteal and other ovarian tissues by incubation in vitro with labelled substrates. Aromatase was undetectable in corpora lutea or in interstitial tissue, but was present in the ovarian tissues (including follicles) which remained after removal of corpora lutea. The probable source of the oestrogens detected in the corpus luteum is discussed in relation to their role in the inhibition of follicular development during embyronic diapause.

Androstenedione↗
PubMed1983

Embryonic steroid synthesis and luteal oxytocin production: controlling mechanisms for the maternal recognition of pregnancy.

In both pigs and sheep in early pregnancy the function of the corpora lutea is maintained beyond the normal time of luteal regression. The mechanism by which this is brought about appears in both species to involve reduced uterine secretion of the uterine luteolysin, prostaglandin F2 alpha, as a result of the secretion of an embryonic antiluteolysin. In the pig this antiluteolysin is an oestrogen, and in the sheep, the protein trophoblastin. Loss of luteal oxytocin also occurs in sheep early in pregnancy, and this may contribute to reduced luteolytic drive during the period between 25 and 50 days of gestation when the embryonic antiluteolysin is absent. Concentrations of oxytocin in the corpora lutea appear to be controlled by a factor of uterine origin, since luteal oxytocin is also depleted after hysterectomy.

Animals↗
PubMed1983

Effects of the embryo upon endometrial estrogen synthesis in the rabbit.

To analyze for the possible embryonic effects upon endometrial estrogen synthesis (estrone, estradiol, estrone sulfate and estradiol sulfate), endometrial samples from each horn of unilaterally tubal-ligated estrous, pseudopregnant and pregnant rabbits were incubated with [3H] progesterone or [3H] androstenedione on Days 0, and 3 to 8 postcoitum. No endometrial estrogen synthesis was detected on Day 0, or on Days 3 to 5 of pseudopregnancy but low levels of estrogens (less than 0.7 pg/g wet wt) were detectable from androstenedione metabolism when individual samples were pooled (n=4 per day) for Days 6, 7 and 8 of pseudopregnancy. Low levels of estrogen synthesized from the pseudopregnant endometrium may represent a latent capability without the required stimulation for active synthesis. In pregnant animals, incubation of the gravid horn endometrium with either substrate produced similar trends of estrogen synthesis, in that estrogen levels increased at Days 4 to 5 (P less than 0.01), stabilized until Day 7 when levels decreased and then further increased on Day 8 (P less than 0.05). Estrogen synthesis by the endometrium of the nongravid horn was generally lower (P less than 0.05) than the gravid horn and stabilized or decreased as pregnancy progressed. Increased estrogen synthesis by the endometrium from pregnant rabbits and particularly from the gravid horn denotes a possible relationship between the developing embryo and endometrial estrogen synthesis.

Androstenedione↗