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Biomedical subjects

R B Heap

Publications and source records attributed to R B Heap.

At least 109 records · Page 6Linked to original sources

Progesterone-binding proteins in plasma of guinea-pigs and other hystricomorph rodents.

Progesterone-binding plasma proteins (PBPP, progesterone-binding globulin, PBG, and corticosteroid binding globulin, CBG) have been measured in plasma of guinea-pigs, casiragua, cuis, degu and plains viscacha. During pregnancy PBPP increased to reach peak values between Days 20-25 and Days 50-term in guinea-pigs, immediately before parturition in casiragua, and in mid-gestation in cuis, degu and viscacha. The pattern of PBPP concentration during pregnancy was similar to that of plasma progesterone concentration, and the ratio of molar concentration of PBPP and progesterone was greater than 1 in all species. Plasma proteins were separated by chromatography on SP-Sephadex C-50, and from its chromatographic behaviour and progesterone-binding property evidence was obtained for an anionic, high-affinity PBG in the plasma of all the animals studied during gestation: Electrophoretic mobility of SP-Sephadex-purified PBG applied to 7% polyacrylamide gels differed between species, being highest for casiragua PBG and lowest for guinea-pig PBG. Binding capacities ranged from 0.5 to 4.8 X 10(-6) M, and association constants from 7.6 to 17.4 X 10(8) M-1. Ligand specificities differed between species and marked contrasts were found for certain steroid isomers. The average molecular weights measured by gel electrophoresis of PBG under denaturing conditions were similar in cuis, degu and viscacha and close to PBG I of guinea-pigs, while coypu PBG had a molecular weight of about one half, approximately 75000. It is concluded that PBG has been adopted in pregnancy as a progesterone-conserving mechanism in this suborder of rodents with long gestation periods relative to maternal body weight. Restricted homologies in the physico-chemical characteristics of PBG from various hystricomorph rodents suggest that interspecific differences in structure are considerable.

Alpha-Globulins↗

Migration of binucleate cells in the sheep placenta during normal pregnancy.

The maternofetal interface in the placentomes of the sheep placenta consists of a fetal cellular chorion layer whose apical microvilli interdigitate with those of a syncytial layer which borders the maternal connective tissue. Most of the granulated binucleate cells found in the chorion epithelium reach neither its basement membrane nor its microvillar junction apex. However, up to one fifth of the binucleate cells can be shown to be part of or push pseudopodia across the microvillar junction or are located within the syncytium. The syncytium and chorionic binucleate cells both have a nuclear chromatin structure and distinctive cytoplasmic granules which are not found in any other placental cells. This suggests that most, if not all, of the syncytium is derived by fusion of fetal binucleate cells which have migrated across the microvillar junction from the chorion, and that the immunological maternofetal junction does not lie between chorion and syncytial layers.

Animals↗

Oestrogen production by blastocyst and early embryonic tissue of various species.

Oestrogen synthesis by the early embryo in vitro was studied with tissue from pigs, sheep, cows, roe deer, ferrets, cats, rabbits and a plains viscacha. Definitive evidence for aromatase activity and oestrogen synthesis in preimplantation trophoblast was obtained for the pig with the formation of oestrone, oestradiol-17 beta and oestradiol-17 alpha from 3H-labelled androstenedione and dehydroepiandrosterone. Aromatase activity was appreciably lower in all other species studied, and labelled oestrogens were recovered only from incubations of allantochorionic tissue of roe deer, recovered shortly after implantation, and from pooled samples of early embryonic tissue of cows. High aromatase activity in preimplantation trophoblast of pigs was associated with the maternal recognition of pregnancy and the occurrence of superficial implantation in this species.

Androstenedione↗

Activation by corticosteroids of steriod metabolizing enzymes in ovine placental explans in vitro.

A technique has been developed for the study of placetal steroid synethesis in tissue culture. Explants of sheep placentas recovered in the last third of gestation produced progesterone and converted labelled androstenedione into unconjugated and conjugated oestrogens. Cortisol added to the medium stimulated 17 alpha-hydroxylase and aromatizing enzyme activities. The results are discussed in relation to the proposal that the rise in secretion of fetal cortisol before parturition has a direct effect on the activation of placental enzymes catalysing the conversion of progesterone to eostrogens.

Androstenedione↗

Steroid metabolism in the yolk sac placenta and endometrium of the tammar wallaby, Macropus eugenii.

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 degrees 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 5 alpha-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.

Androstenedione↗

Blastocyst oestrogen synthesis and the maternal recognition of pregnancy.

The maternal recognition of pregnancy takes a number of forms in different species; among the eutherian mammals the maintenance of luteal function and cessation of oestrous or menstrual cycles is an important event in early pregnancy. In the pig the embryos signal their presence in the uterus between Days 10 and 12 post coitum; this time corresponds to the onset of blastocyst synthesis of oestrogens, which are luteotrophic in this species, and it has been suggested that oestrogens may constitute an embryonic signal responsible for maintained luteal function in pregnancy. Although oestrone sulphate, which is formed from oestrogens of embryonic origin by uterine sulphotransferase, has been found in the maternal circulation in high concentrations after Day 15 p.c., its appearance is late relative to the time of maternal recognition of pregnancy. Therefore an alternative mechanism has been sought. The recent finding that oestradiol is capable of reducing uterine prostaglandin F2 alpha secretion (i.e. acting as an antiluteolysin), and that it is present in uterine venous blood as early as Day 12 p.c. in pregnant pigs, suggests a mechanism whereby blastocyst oestrogens may be capable of influencing luteal function.

Androstenedione↗

Pituitary responsiveness to LH-RH and TRH and the effects of progesterone or progesterone and oestradiol treatment in anoestrous sheep.

Pituitary responsiveness to 200 microgram synthetic LH-RH and to 10 microgram TRH was determined in anoestrous sheep before and after treatment for 3 weeks with progesterone (100 mg/day), or oestradiol (250 microgram/day) plus progesterone (100 mg/day). There was a marked decrease in pituitary responsiveness to LH-RH after progesterone (P is less than 0.01), or oestradiol plus progesterone (P is less than 0.01) treatments, and an increase in response to TRH after oestradiol plus progesterone (P is less than 0.01) treatment. The results demonstrate selective and simultaneous feedback effects of oestradiol and progesterone on pituitary responsiveness to two hypothalamic releasing hormones.

Anestrus↗

Progesterone secretion during pregnancy in sheep with an autotransplanted adrenal and an autotransplanted ovary.

Secretion rates by the major sites of progesterone synthesis were measured during pregnancy in 3 ewes with single fetuses after autotransplantation of the left adrenal and the left ovary (containing the corpus luteum) to the neck. The total production of progesterone measured by tracer kinetics increased from 12.1 +/- 2.0 (s.e.m.) to 31.3 +/- 2.4 microgram/min between 66--103 and 133--145 days p.c. Ovarian and adrenal secretion rates measured directly at the same times decreased from 5.2 +/- 0.9 to 2.1 +/- 0.9 microgram/min (ovary), or remained unchanged, about 0.03 microgrom/min (adrenal). The difference between the total production of progesterone and ovarian and adrenal secretion showed that the contribution from other endocrine tissues (presumably the placenta) increased from 6.8 +/- 1.5 to 29.2 +/- 4.1 microgram/min (P less than 0.001) during this period.

Adrenal Glands↗

Progesterone and oestrogen in pregnancy and parturition: comparative aspects and hierarchical control.

The different ways in which the progesterone requirements of pregnancy are met in various species are reviewed here. Progesterone production expressed in terms of metabolic body weight lies within about one order of magnitude in several species (but not in the rat), whether the hormone is predominantly ovarian or placental in origin. Parturition is usually preceded by a decrease in the plasma concentration of progesterone and the evidence which suggests that a decrease in secretion involves enzyme induction is summarized. In the sheep a sequence of well-marked hormonal changes can be discerned--an increase in fetal cortisol secretion followed by a fall in placental progesterone and a rise in oestrogen and prostaglandin F2alpha secretion. This sequence has been interpreted in terms of hierarchical control theory which envisages a series of levels placed in a descending order of importance and in which there is a downward transmission of a signal from a higher level that modifies activity at a lower level. A dominant level in the hierarchy in the sheep and pig seems to be the fetal hypothalamus and pituitary, but in the rabbit the maternal hypothalamus, pituitary and ovary play a more dominant role.

Adrenal Glands↗

Pituitary responsiveness to synthetic LH-RH and pituitary LH content at various reproductive stages in the sheep.

In sheep the basal concentration of LH in jugular vein plasma was significantly higher during the first 50 days of gestation in late pregnancy or at parturition. The pituitary response to a single i.v. injection of 200 microng synthetic LH-RH was determined at different stages of gestation and compared with that of anoestrous and cyclic sheep. Pituitary response to LH-RH decreased progressively with advancing gestation: by 56 days after mating the response had declined to 35% and by parturition to 14% of the value in anoestrous sheep. The pituitary response to LH-RH increased after parturition and the pattern of recovery differed in non-lactating and lactating sheep. By 63 days postpartum the response to LH-RH in non-lactating and lactating animals had returned to values similar to those in sheep during anoestrus and sheep during the luteal phase of the oestrous cycle. A decrease in pituitary responsiveness during pregnancy was associated with a decrease in pituitary content of LH. The quantity of LH released in response to a standard injection of LH-RH was linearly related to pituitary LH content.

Animals↗

Progesterone and 20 alpha-dihydroprogesterone in sheep: a model of their distribution and metabolism.

The rates of metabolism of progesterone and 20alpha-dihydroprogesterone (20alpha-diHP) in sheep have been measured during and after the infusion of tracer amounts of [3H]progesterone. There were significant differences in the blood concentration of [3H]progesterone between experiments, but these were not attributable to the stage of gestation or to the difference between pregnant and non-pregnant animals. The mean (+/- S.E.M.) metabolic clearance rate of progesterone was 3-277 +/- 0-239 litres blood/min. The simplest model of the distribution of progesterone was one containing two pools, V1[P] and V2[P], where [p] is the blood concentration of progesterone, and in 23 experiments on 7 sheep the mean pool dimensions were 7-8[P] mug and 70[P] mug, respectively. This model was developed to include the formation of 20alpha-diHP from progesterone. Progesterone appeared to be the major source of 20alpha-diHP, though this did not seem to be an obligatory metabolite. The parameters obtained gave comparably low residual deviations for both labelled steroids and were consistent with other observations made on progesterone clearance.

20-alpha-Dihydroprogesterone↗