Search Results
You are looking at 1 - 6 of 6 items for
- Author: R. D. BURTON x
- Refine by access: All content x
Search for other papers by A. P. F. Flint in
Google Scholar
PubMed
Search for other papers by R. D. Burton in
Google Scholar
PubMed
ABSTRACT
The cytosolic glucocorticoid receptor of ovine placental zona intima has been characterized and measured between day 51 of pregnancy and term, and levels compared with those in fetal lung. By ion-exchange and gel-filtration chromatography the molybdate-stabilized receptor was found to be an acidic molecule with Stokes radius approximately 8 nm; these physicochemical characteristics of the ovine placental receptor are comparable to those of receptors in glucocorticoid target tissues from non-ruminants. Concentrations of cytosolic receptor in placenta (mean, 139 fmol/mg protein) were lower than those in fetal lung (627 fmol/mg) at all stages of gestation investigated. To some extent this difference was accounted for by a twofold higher concentration of protein in placental cytosols compared with those from fetal lung. In both tissues, cytosolic receptor concentrations were maximal between days 91 and 130, when fetal adrenal steroid secretion is low; receptor concentrations decreased before term. Fetal hypophysectomy, which resulted in prolonged gestation, raised receptor concentrations in placenta, but not in fetal lung. In both tissues, apparent dissociation constants for [3H]dexamethasone binding to glucocorticoid receptors were in the range 0·5–7·1 nmol/l; these dissociation constants did not change consistently between day 100 and term. In whole-cell preparations of placenta and fetal lung incubated in vitro there was time-dependent specific binding of [3H]dexamethasone by nuclei, and binding of labelled cytosolic receptor to isolated nuclei occurred at all stages of gestation investigated. Binding of [3H]dexamethasone by cytosolic receptor from placenta and fetal lung was inhibited by progesterone and 17α-hydroxyprogesterone, as well as by cortisol, cortisone, 11-deoxycorticosterone and 11β-hydroxyprogesterone; 20α-hydroxyprogesterone and 17α,20α-dihydroxypregn-4-en-3-one were less effective. In experiments to evaluate the possible antagonistic action of progesterone in whole-cell preparations, uptake of [3H]dexamethasone by nuclei was increased up to twofold in placental minces incubated with aminoglutethimide or epostane, when progesterone synthesis was reduced by 98 and 92 per cent respectively. Nuclear uptake in minces of fetal lung was blocked by concentrations of progesterone found in placenta. The existence of a placental glucocorticoid receptor confirms that fetal cortisol may act directly on the placenta to induce the enzymatic changes controlling the onset of labour. Its availability early in pregnancy is consistent with the ability of administered glucocorticoid to induce labour at any time after day 90 of gestation. Progesterone in the placenta may act as a glucocorticoid antagonist, protecting the fetus against inappropriate induction of preterm labour resulting from high levels of glucocorticoids in the maternal circulation.
J. Endocr. (1984) 103, 31–42
Search for other papers by R. B. HEAP in
Google Scholar
PubMed
Search for other papers by M. B. RENFREE in
Google Scholar
PubMed
Search for other papers by R. D. BURTON in
Google Scholar
PubMed
Yolk sac and endometrial tissue were obtained from tammar wallabies between 11 and 25 days after the removal of pouch young. Tissues were examined histologically and steroid-metabolizing enzymes were identified by incubation for 3 h at 37 °C in Medium 199 containing labelled steroid precursors. Yolk sac membrane (YSM) incubated with labelled pregnenolone produced a small amount of progesterone and pregnanediols; 80·5 ± 8·4 (s.e.m.) % of the original substrate remained unmetabolized. Labelled androstenedione was metabolized to 5α-androstane-3,17-dione and androsterone, and only 5·8 ± 3·8% of the original substrate remained at the end of incubation. Incorporation of androstenedione or dehydroepiandrosterone (DHA) into phenolic compounds was low (0·5 ± 0·1%). There was no evidence for the enzymes, arylsulphatase or sulphotransferase, in YSM. Endometrial tissue from the same animals metabolized pregnenolone, DHA and androstenedione, converted progesterone to androstenedione, and produced aqueous-soluble steroid conjugates. The results demonstrated that YSM contains enzymes associated predominantly with steroid catabolism and with incipient progesterone synthesis. The findings are discussed in relation to the histological appearance of the tissues and compared with placental steroid synthesis in eutherian mammals.
Search for other papers by A. P. F. Flint in
Google Scholar
PubMed
Search for other papers by R. D. Burton in
Google Scholar
PubMed
Search for other papers by R. B. Heap in
Google Scholar
PubMed
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 3β-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.
Search for other papers by A. M. BURTON in
Google Scholar
PubMed
Search for other papers by D. V. ILLINGWORTH in
Google Scholar
PubMed
Search for other papers by J. R. G. CHALLIS in
Google Scholar
PubMed
Search for other papers by A. S. McNEILLY in
Google Scholar
PubMed
SUMMARY
Oxytocin levels in pregnant and parturient guinea-pigs were studied by means of a sensitive and specific radioimmunoassay. Oxytocin was released from the maternal pituitary in substantial amount only during the expulsive phase of labour, when the mean concentration in carotid arterial blood in five animals was 503 pg/ml plasma (range 96–2900 pg/ml). Oxytocin was not found in the plasma of the first born at the moment of birth, but was usually detected in amounts ranging from 96 to 455 pg/ml in those born subsequently. The mean half-time of oxytocin in the maternal circulation during late pregnancy was 62 ± 7·5 (s.e.m., n = 5) s. In-vivo experiments showed that the placenta was permeable to oxytocin in both directions.
Search for other papers by D. V. ILLINGWORTH in
Google Scholar
PubMed
Search for other papers by J. R. G. CHALLIS in
Google Scholar
PubMed
Search for other papers by N. ACKLAND in
Google Scholar
PubMed
Search for other papers by A. M. BURTON in
Google Scholar
PubMed
Search for other papers by R. B. HEAP in
Google Scholar
PubMed
Search for other papers by J. S. PERRY in
Google Scholar
PubMed
SUMMARY
Parturition in the guinea-pig is not preceded by any consistent change in the maternal plasma concentrations of progesterone, total unconjugated oestrogens or corticosteroids, or by a significant change in the concentration of progesterone-binding globulin (PBG). The onset of parturition was delayed by high doses of oestrogens (stilboestrol and oestradiol), but was not affected by oestriol or an antiserum raised against oestradiol. Premature parturition was achieved by the intra-carotid infusion of adrenocorticotrophin or prostaglandins (PGF2α, PGE2, I.C.I. 80,996) in conscious animals with indwelling catheters. I.C.I. 80,996, a potent analogue of PGF2α, induced parturition in all seven guinea-pigs treated; delivery occurred within 6 h of starting the infusion in six animals, and within 48 h in the seventh. The undesirable side-effects that accompanied treatment with PGF2α or PGE2 were not encountered with I.C.I. 80,996. Parturition induced experimentally resembled normal delivery but was not preceded by any significant change in the maternal levels of progesterone, total unconjugated oestrogens, corticosteroids, PBG or CBG in the circulation. Oxytocin was not detected until the delivery of the first foetus.
Parturition was not induced by maternal or foetal injections of corticosteroids or dexamethasone. Earlier findings are confirmed that the foetal adrenal grows steadily throughout late pregnancy and, unlike the foetal lamb adrenal, undergoes no rapid phase of growth immediately before term. Foetal adrenal weight decreased relative to foetal body weight.
The trigger for parturition in this species remains unidentified.
Search for other papers by X. Zhao in
Google Scholar
PubMed
Search for other papers by B. W. McBride in
Google Scholar
PubMed
Search for other papers by I. Politis in
Google Scholar
PubMed
Search for other papers by H. T. Huynh in
Google Scholar
PubMed
Search for other papers by R. M. Akers in
Google Scholar
PubMed
Search for other papers by J. H. Burton in
Google Scholar
PubMed
Search for other papers by J. D. Turner in
Google Scholar
PubMed
ABSTRACT
Insulin-like growth factor-I (IGF-I) has been known to be mitogenic to a variety of cell types, although a growth-regulatory role for IGF-I on bovine mammary epithelial cells has not been fully investigated. In the present study, we examined the receptor binding of IGF-I and its effect on growth in a bovine mammary epithelial cell line (MAC-T3). Specific receptors for IGF-I were detected on cultured bovine mammary epithelial cells. Competitive binding revealed that half-maximal inhibition of 125I-labelled IGF-I binding by IGF-I was approximately 3 μg/l. Dissociation rate constant of the IGF-I receptor was 3·10±0·06 nmol/l (s.e.m.) with a receptor site concentration of 366 ± 8 fmol/mg protein for the average of three experiments. IGF-I exerted a positive mitogenic effect on MAC-T3 cells according to both direct DNA assay and thymidine incorporation assay. Moreover, the mitogenic effect of IGF-I on MAC-T3 cells was enhanced by the addition of fetal calf serum in the culture media. The present results suggest that the bovine mammary epithelial cell line (MAC-T3) provides a useful model system with which to study the biological actions of insulin-like growth factors on the bovine mammary secretory tissue in vitro.
Journal of Endocrinology (1992) 134, 307–312
