PLACENTAL PRODUCTION OF 5β-PREGNANE-3α,20α-DIOL IN GOATS

1981 ◽  
Vol 90 (2) ◽  
pp. 151-158 ◽  
Author(s):  
E. L. SHELDRICK ◽  
A. P. RICKETTS ◽  
A. P. F. FLINT
Keyword(s):  
Medroxyprogesterone Acetate ◽  
Plasma Concentrations ◽  
Placental Tissue ◽  
Late Pregnancy ◽  
Repeated Administration ◽  
Peripheral Circulation ◽  
Major Product ◽  
Progesterone Metabolism ◽  
Reductive Metabolism

A major product of progesterone metabolism by the goat placenta in vitro was found to be 5β-pregnane-3α,20α-diol. The concentration of this steroid has been measured by radioimmunoassay in the peripheral circulation during pregnancy. Peripheral plasma concentrations of 5β-pregnane-3α,20α-diol were low (less than 6 nmol/l) in anoestrous and non-pregnant ovariectomized goats, and during the first month of pregnancy but increased progressively after day 45 of pregnancy, reaching 78–94 nmol/l between days 112 and 142. Thereafter levels declined before term. Changes in the plasma concentration of 5β-pregnane-3α,20α-diol during pregnancy in the goat therefore resembled those of progesterone in the sheep. Plasma concentrations of 5β-pregnane-3α,20α-diol between day 70 and term were not influenced by repeated administration of medroxyprogesterone acetate from days 51 to 82 or by lutectomy in goats treated with medroxyprogesterone acetate. Secretion of 5β-pregnane-3α,20α-diol by the uterus and its contents was indicated by a positive venous–arterial difference across the uterus between days 128 and 141 in three ovariectomized pregnant goats receiving medroxyprogesterone acetate. Comparison of the rates of metabolism of progesterone by homogenates of placenta in vitro showed that the placental tissue from goats was three times more active in this respect than was tissue from sheep. The ratio of the plasma concentrations of 5β-pregnane-3α,20α-diol and progesterone in late pregnancy in ovariectomized or lutectomized goats exceeded by a factor of 10 that in sheep at a comparable stage of gestation. It is suggested that reductive metabolism of progesterone before it is secreted may account for the inability of the placenta to maintain pregnancy after ovariectomy in goats.

Genotype and fetal size affect maternal­–fetal amino acid status and fetal endocrinology in Large White×Landrace and Meishan pigs

2013 ◽  
Vol 25 (2) ◽  
pp. 439 ◽  
Author(s):  
Cheryl J. Ashworth ◽  
Margaret O. Nwagwu ◽  
Harry J. McArdle
Keyword(s):  
Amino Acid ◽  
Plasma Concentrations ◽  
Placental Tissue ◽  
Maternal Plasma ◽  
Plasma Amino Acid ◽  
Large White ◽  
Fetal Plasma ◽  
Acid Status ◽  
Fetal Size

This study compared maternal plasma amino acid concentrations, placental protein secretion in vitro and fetal body composition and plasma amino acid and hormone concentrations in feto–placental units from the smallest and a normally-sized fetus carried by Large White × Landrace or Meishan gilts on Day 100 of pregnancy. Compared with Large White × Landrace, Meishan placental tissue secreted more protein and Meishan fetuses contained relatively more fat and protein, but less moisture. Fetal plasma concentrations of insulin, triiodothryonine, thyroxine and insulin-like growth factor (IGF)-II were higher in Meishan than Large White × Landrace fetuses. In both breeds, fetal cortisol concentrations were inversely related to fetal size, whereas concentrations of IGF-I were higher in average-sized fetuses. Concentrations of 10 amino acids were higher in Large White × Landrace than Meishan gilts, while glutamine concentrations were higher in Meishan gilts. Concentrations of alanine, aspartic acid, glutamic acid and threonine were higher in Meishan than Large White × Landrace fetuses. Average-sized fetuses had higher concentrations of asparagine, leucine, lysine, phenylalanine, threonine, tyrosine and valine than the smallest fetus. This study revealed novel genotype and fetal size differences in porcine maternal–fetal amino acid status and fetal hormone and metabolite concentrations.

High concentrations of immunoreactive inhibin in the plasma of mares and fetal gonads during the second half of pregnancy

1996 ◽  
Vol 8 (8) ◽  
pp. 1137 ◽  
Author(s):  
Y Nambo ◽  
S Nagata ◽  
M Oikawa ◽  
T Yoshihara ◽  
N Tsunoda ◽  
...  
Keyword(s):  
Immunohistochemical Staining ◽  
Follicle Stimulating Hormone ◽  
Plasma Concentrations ◽  
Peripheral Circulation ◽  
Pituitary Cells ◽  
Rat Pituitary ◽  
High Concentrations ◽  
Rat Pituitary Cells ◽  
First Time

Plasma concentrations of immunoreactive (ir)-inhibin were measured in seven pregnant mares from around Day 140 of gestation to Day 2 after parturition using a heterologous bovine-based radioimmunoassay (RIA). Concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol-17 beta, progesterone and relaxin were also measured in the same samples. A marked increase in plasma concentrations of ir-inhibin, FSH and LH occurred between Day 220 and Day 300 of gestation but the concentrations of all three hormones returned to baseline by about Day 320 (three weeks before parturition). In contrast, circulating concentrations of the three placental hormones, oestradiol-17 beta, progesterone and relaxin, increased during the final weeks of pregnancy and then decreased markedly to basal values within two days of parturition. There was a positive correlation between circulating concentrations of ir-inhibin and FSH (r = 0.75, P < 0.01) rather than the expected negative correlation. ir-inhibin was not detected in homogenates obtained at Day 190 of pregnancy and form term placenta, but high concentrations of ir-inhibin were present in homogenates of fetal and newborn gonads. Despite the high concentrations of ir-inhibin in these homogenates, they failed to exert any suppressive bioactivity on FSH secretion by rat pituitary cells cultured in vitro. Furthermore, immunohistochemical staining revealed the presence of inhibin in the interstitial cells of equine fetal gonads at Day 190 of gestation. These findings demonstrate for the first time that high concentrations of ir-inhibin, LH and FSH are secreted into the peripheral circulation of the mare during the second half of pregnancy. However, ir-inhibin present in the plasma of pregnant mares appears to be biologically inactive. This hormone is not presumed to be of placental origin but it is proposed that either the enlarged fetal gonads or the maternal ovaries, or both of these organs, may be a source of inhibin in response to the coincident increase in circulating concentrations of LH and FSH.

Effects of prenatal administration of mestranol and two progestins on testosterone synthesis and reproductive tract development in male rats

1987 ◽  
Vol 116 (2) ◽  
pp. 193-199 ◽  
Author(s):  
Santosh K. Varma ◽  
Eric Bloch
Keyword(s):  
Body Weight ◽  
Seminal Vesicle ◽  
Medroxyprogesterone Acetate ◽  
Placental Tissue ◽  
Endocrine Function ◽  
Male Rats ◽  
Ventral Prostate ◽  
Pregnant Rats ◽  
Testosterone Synthesis

Abstract. The oestrogen mestranol (0, 0.01, 0.1 mg/kg body weight per day) and the progestins medroxyprogesterone-acetate and norethisterone (0, 2, 20 mg/kg body weight per day each) in sesame oil were intubated intragastrically daily during gestational days 14.5 through 19.5 to pregnant rats. Males were studied as 20.5-day-old foetuses and 4-month-old adults for serum testosterone and LH concentrations, in vitro testosterone synthesis, anogenital distance (foetuses only) and testes, seminal vesicle and ventral prostate weights. Administration of 0.1 mg mestranol decreased by 35 to 70% basal and LH-stimulated testosterone synthesis by both foetal and adult testes in vitro (P < 0.01). Foetal body weights (P < 0.05), but not anogenital distances, were significantly decreased. Testosterone content in adult sera was reduced significantly (P < 0.05) to less than 50% of control. Testes, ventral prostate, seminal vesicle and epididymal weights were unaffected by treatment. Medroxyprogesterone acetate or norethisterone administration did not alter testes endocrine function in foetal or adult offspring. In a small number of rats, pregnant for 10.5, 14.5 or 18.5 days, [3H]ethinyloestradiol was intubated and foetal and placental tissue examined for appearance and content of radioactivity. Radioactivity was detected in 10.5, 14.5 and 18.5 days old placentas, and 14.5 and 18.5 days old foetal liver, gonads and external genitalia. With [3H]medroxyprogesterone acetate, radioactivity was localized in 14.5 day placenta and foetal tissues. Thin-layer chromatographic analysis showed most of the activity to migrate as authentic ethinyloestradiol or medroxyprogesterone acetate. The results demonstrate inhibition of testicular testosterone synthesis by mestranol, presumably by being transferred across the placenta and acting in the foetus. The diminished activity of adult testes indicates a permanent effect of in utero mestranol exposure on testes function.

ACTIVITY OF STEROID C-17,20 LYASE IN THE OVINE PLACENTA: EFFECT OF EXPOSURE TO FOETAL GLUCOCORTICOID

1976 ◽  
Vol 69 (2) ◽  
pp. 239-246 ◽  
Author(s):  
PENELOPE A. STEELE ◽  
A. P. F. FLINT ◽  
A. C. TURNBULL
Keyword(s):  
Post Partum ◽  
Late Pregnancy ◽  
Peripheral Circulation ◽  
Ovine Placenta ◽  
Spontaneous Onset

SUMMARY Microsomal fractions isolated from post-partum ovine placentae catalysed the synthesis of [3H]oestrone and [3H]oestradiol from [3H]17α-hydroxyprogesterone and NADPH; oestrone and oestradiol were formed in a ratio of approximately 50:1. The expected intermediate, [3H]androstenedione, did not accumulate during these incubations but was shown by trapping experiments to be the intermediate involved. Mean ( ± s.d.) yields of [3H]oestrone (% conversion of substrate) during incubation for 1 h of placentae from five animals in late pregnancy before the onset of labour, from five animals which delivered spontaneously at term and from four animals in which labour was induced by administration of dexamethasone to the foetus were: in tissue obtained before labour, 3·2 ± 0·44; in tissue obtained after the spontaneous onset of labour, 20·6 ± 10·2 (P < 0·01) and in tissue obtained after dexamethasone-induced labour, 24·4 ± 2·13 (P < 0·001). This increase in oestrone synthesis suggests activation of steroid C-17,20 lyase, since this is the step limiting the rate of synthesis of oestrone in vitro. The enzyme is probably activated by foetal glucocorticoid. The findings are discussed in relation to the site of synthesis of oestrogens which in the sheep increase in concentration in the peripheral circulation at term, and with reference to a possible mechanism by which foetal glucocorticoid may control the onset of labour in this species.

Initiation of parturition and lactation in the sow: effects of delaying parturition with medroxyprogesterone acetate

1990 ◽  
Vol 124 (3) ◽  
pp. 475-484 ◽  
Author(s):  
J. L. Whitely ◽  
P. E. Hartmann ◽  
D. L. Willcox ◽  
G. D. Bryant-Greenwood ◽  
F. C. Greenwood
Keyword(s):  
Medroxyprogesterone Acetate ◽  
Plasma Concentrations ◽  
Late Pregnancy ◽  
Treated Group ◽  
Untreated Group ◽  
Initial Increase ◽  
Plasma Prolactin ◽  
Hormonal Changes ◽  
Gestational Length ◽  
Plasma Progesterone

ABSTRACT The synthetic progestagen, medroxyprogesterone acetate (MPA), was administered to sows in late pregnancy with the objective of slightly delaying the time of farrowing and thereby providing more marked associations between hormonal changes and the termination of pregnancy, and the initiation of farrowing and lactation in this species. MPA was administered orally (140 mg, twice daily) to eight sows in late pregnancy on days 112, 113 and 114 of gestation. Parturition was then induced to occur on day 116 by injecting 200 μg cloprostenol i.m. on day 115 of gestation. The peripartum changes in the plasma concentrations of progesterone, cortisol, oestradiol-17β, relaxin, prolactin, lactose and 13,14-dihydro-15-keto prostaglandin F2α (PGFM) were measured in these sows together with a group of untreated sows. The gestational length for the MPA-treated sows (116·3 ± 0·3 days, mean±s.e.m.) was significantly (P<0·01) greater compared with the untreated sows (114·9 ± 0·3 days). Plasma progesterone declined earlier (P<0·05) with respect to the time of parturition in the treated sows compared with the untreated group. With respect to the timing of parturition, the time at which maximal concentrations of relaxin were attained and the timing of the subsequent decline were earlier in the MPA-treated sows. In both groups of sows, the concentration of relaxin increased before the decline in plasma progesterone. In the untreated sows, the concentration of PGFM increased either slightly before or at the same time as the decline in plasma progesterone, whereas in sows treated with MPA, progesterone concentrations began to decline before any significant increase in the plasma concentration of PGFM. The profiles of cortisol, oestradiol-17β and PGFM were similar in both groups of sows. In both groups of sows, the timing of the initial increase in the concentration of plasma prolactin coincided with a similar rise in plasma lactose (P<0·01). Plasma progesterone either declined earlier or at the same time as the rise in plasma lactose (P<0·01) in the treated group of sows only. We conclude that since the prepartum changes in the concentration of progesterone and relaxin occurred before significant changes in the concentration of PGFM in the MPA-treated sows, the nature of the luteolytic factor and the mechanism by which it exerts its action remains obscure. The higher concentration of lactose in the mammary secretion at birth in the MPA-treated sows compared with the untreated group suggested that lactogenesis was initiated earlier with respect to parturition following MPA treatment. Furthermore, the administration of MPA to sows in late pregnancy delayed the onset of parturition but did not inhibit lactogenesis. Journal of Endocrinology (1990) 124, 475–484

Comparison of Specific Antibody, D-Phe-Pro-Arg-CH2Cl and Aprotinin for Prevention of In Vitro Effects of Recombinant Tissue-Type Plasminogen Activator on Haemostasis Parameters

1987 ◽  
Vol 58 (03) ◽  
pp. 921-926 ◽  
Author(s):  
E Seifried ◽  
P Tanswell
Keyword(s):  
Specific Antibody ◽  
Plasma Concentrations ◽  
Fibrinolytic Therapy ◽  
Tissue Type ◽  
Control Value ◽  
Type Plasminogen Activator ◽  
In Vitro Effects ◽  
Fibrinolytic Parameters

SummaryIn vitro, concentration-dependent effects of rt-PA on a range of coagulation and fibrinolytic assays in thawed plasma samples were investigated. In absence of a fibrinolytic inhibitor, 2 μg rt-PA/ml blood (3.4 μg/ml plasma) caused prolongation of clotting time assays and decreases of plasminogen (to 44% of the control value), fibrinogen (to 27%), α2-antiplasmin (to 5%), FV (to 67%), FVIII (to 41%) and FXIII (to 16%).Of three inhibitors tested, a specific polyclonal anti-rt-PA antibody prevented interferences in all fibrinolytic and most clotting assays. D-Phe-Pro-Arg-CH2Cl (PPACK) enabled correct assays of fibrinogen and fibrinolytic parameters but interfered with coagulometric assays dependent on endogenous thrombin generation. Aprotinin was suitable only for a restricted range of both assay types.Most in vitro effects were observed only with rt-PA plasma concentrations in excess of therapeutic values. Nevertheless it is concluded that for clinical application, collection of blood samples on either specific antibody or PPACK is essential for a correct assessment of in vivo effects of rt-PA on the haemostatic system in patients undergoing fibrinolytic therapy.

METABOLISM OF 17α-HYDROXYPROGESTERONE-4-14C-17α-CAPROATE BY HOMOGENATES OF RAT LIVER AND HUMAN PLACENTA

1961 ◽  
Vol 36 (4) ◽  
pp. 511-519 ◽  
Author(s):  
Margaret Wiener ◽  
Charles I. Lupa ◽  
E. Jürgen Plotz
Keyword(s):  
Rat Liver ◽  
Human Placenta ◽  
Steric Hindrance ◽  
Placental Tissue ◽  
Caproic Acid ◽  
Major Product ◽  
Side Chain ◽  
Anaerobic Conditions ◽  
Prolonged Action ◽  
Long Acting

ABSTRACT 17α-hydroxyprogesterone-4-14C-17α-caproate (HPC), a long-acting progestational agent, was incubated with homogenates of rat liver and human placenta. The rat liver was found to reduce Ring A of HPC under anaerobic conditions to form allopregnane-3β,17α-diol-20-one-17α-caproate and pregnane-3β,17α-diol-20-one-17α-caproate, the allopregnane isomer being the major product. The caproic acid ester was neither removed nor altered during the incubation. Placental tissue did not attack HPC under conditions where the 20-ketone of progesterone was reduced. It is postulated that this absence of attack on the side chain is due to steric hindrance from the caproate ester, and that this may account for the prolonged action of HPC.

DEPENDENCE OF IN VITRO PROGESTERONE METABOLISM ON PROTEIN BINDING IN THE RAT UTERUS

1974 ◽  
Vol 77 (1_Suppl) ◽  
pp. S86
Author(s):  
D. Egert ◽  
W. Jonat ◽  
H. Maass
Keyword(s):  
Protein Binding ◽  
Rat Uterus ◽  
Progesterone Metabolism

Evidence for episodic GnRH-modulated hCG secretion by placental tissue in vitro

1989 ◽  
Vol 120 (3_Suppl) ◽  
pp. S103 ◽  
Author(s):  
W. E. MERZ ◽  
C. ERLEWEIN ◽  
P. LICHT ◽  
T. O. F. WAGNER
Keyword(s):  
Placental Tissue ◽  
Hcg Secretion

In vivo Evaluation and Alzheimer’s Disease Treatment Outcome of siRNA Loaded Dual Targeting Drug Delivery System

2019 ◽  
Vol 20 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Chi Zhang ◽  
Zhichun Gu ◽  
Long Shen ◽  
Xianyan Liu ◽  
Houwen Lin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Outcome ◽  
Neuroprotective Effect ◽  
Sirna Delivery ◽  
Repeated Administration ◽  
Spatial Learning And Memory ◽  
In Vivo Evaluation

Background: To deliver drugs to treat Alzheimer’s Disease (AD), nanoparticles should firstly penetrate through blood brain barrier, and then target neurons. Methods: Recently, we developed an Apo A-I and NL4 dual modified nanoparticle (ANNP) to deliver beta-amyloid converting enzyme 1 (BACE1) siRNA. Although promising in vitro results were obtained, the in vivo performance was not clear. Therefore, in this study, we further evaluated the in vivo neuroprotective effect and toxicity of the ANNP/siRNA. The ANNP/siRNA was 80.6 nm with good stability when incubated with serum. In vivo, the treatment with ANNP/siRNA significantly improves the spatial learning and memory of APP/PS1 double transgenic mice, as determined by mean escape latency, times of crossing the platform area during the 60 s swimming and the percentage of the distance in the target quadrant. Results and Conclusion: After the treatment, BACE1 RNA level of ANNP/siRNA group was greatly reduced, which contributed a good AD treatment outcome. Finally, after repeated administration, the ANNP/siRNA did not lead to significant change as observed by HE staining of main organs, suggesting the good biocompatibility of ANNP/siRNA. These results demonstrated that the ANNP was a good candidate for AD targeting siRNA delivery.

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