scholarly journals Potent inhibition of mammalian progesterone synthesis by 2 α-cyanoprogesterone

1985 ◽  
Vol 230 (3) ◽  
pp. 587-594 ◽  
Author(s):  
R B Sharp ◽  
M B Senior ◽  
T M Penning
Keyword(s):  
Corpus Luteum ◽  
Adrenal Cortex ◽  
Tight Binding ◽  
Competitive Inhibitor ◽  
Selective Inhibitor ◽  
Corpora Lutea ◽  
Progesterone Synthesis ◽  
Ic50 Values ◽  
Human Progesterone Receptor

2 α-Cyanoprogesterone potently inhibits the conversion of [3H]pregnenolone into progesterone catalysed by bovine corpora lutea, bovine adrenal cortex and human term placenta microsomes (microsomal fractions), yielding IC50 (concentration causing 50% inhibition) values of 66 nM, 120 nM and 700 nM respectively. By contrast, it is an exceedingly poor inhibitor of the isomerization of pregn-5-ene-3,20-dione, yielding IC50 values between 50 and 70 microM. On this basis, 2 α-cyanoprogesterone would appear to be an extraordinarily selective inhibitor of the 3 β-hydroxysteroid dehydrogenase. Dixon plots indicate that it is a very-tight-binding competitive inhibitor of the corpus-luteum enzyme, yielding a Ki of 15 nM. In the bovine adrenal cortex and human placenta the steroid is less potent and inhibits the dehydrogenase non-competitively with Ki values of 150 nM and 1.0 microM respectively. Thus 2 α-cyanoprogesterone inhibits the corpus-luteum dehydrogenase with substantial selectivity. Because of its high affinity for the ovarian enzyme, the presence of low-micromolar concentrations of 2 α-cyanoprogesterone can promote a complete cessation of progesterone synthesis in corpora-lutea microsomes for several hours. Since this effect is observed in the presence of saturating concentrations of pregnenolone (50 microM), it is predicted that this inhibitor may be even more potent in vivo. 2 α-Cyanoprogesterone displays very low affinity for the human progesterone receptor, yielding a Kd of 600 nM as against a Kd of 1.6 nM for progesterone. It is suggested that 2 α-cyanoprogesterone may be a selective inhibitor of ovarian progesterone synthesis and may act as an effective anti-gestational agent in vivo.

PROPERTIES OF HUMAN GONADOTROPHINS ELUTED FROM HUMAN CORPUS LUTEUM AND MOUSE LUTEOMA LH-HCG RECEPTORS

1977 ◽  
Vol 84 (1) ◽  
pp. 142-154 ◽  
Author(s):  
F. E. Cole ◽  
P. C. Arquembourg ◽  
B. F. Rice
Keyword(s):  
Corpus Luteum ◽  
Electrophoretic Mobility ◽  
Present Report ◽  
Corpora Lutea ◽  
Fresh Tissue ◽  
Mouse Tissues ◽  
Tissue Receptors ◽  
Human Corpus Luteum

ABSTRACT Studies were performed to try to determine if gonadotrophins are altered during their interaction with tissue receptors. Immunologic, electrophoretic and binding properties of lactoperoxidase labelled [125I]HLH and [125I]HCG were examined before and after elution from mouse luteoma and human corpora lutea receptor preparations. The anti-HCG used in these studies at a 1:10 000 dilution precipitated 92% of a freshly iodinated [125I]HCG preparation. Receptor eluted [125I]HCG, derived from the same batch of labelled ligand, was virtually quantitatively precipitated by the same dilution of anti-HCG. [125I]HCG eluted from the human corpus luteum was electrophoretically more homogenous when compared to its heterogenous parent labelled preparation and migrated to a position similar to that of native HCG. In Ouchterlony double diffusion experiments against anti-HCG antiserum, corpus luteum eluted [125I]HCG and [125I]HLH showed immunologic identity with each other as well as with native HCG and HLH. Receptor eluted [125I]HCG from the mouse luteoma, following in vivo administration via tail vein injection or after incubation in vitro with labelled hormones, was immunologically indistinguishable from native HCG. The electrophoretic mobility of HCG was retarded when HCG was added to extracts of mouse luteoma, liver and kidney. Eluates of mouse luteoma, applied to Bio-Gel columns previously equilibrated with [125I]HCG showed the ability to concentrate [125I]HCG in the high molecular weight column fractions. Similar results were obtained with columns equilibrated with [125I]TSH and [125I]HGH. [125I]HCG eluted from the mouse luteoma was able to bind to fresh luteoma homogenate but, in contrast to an earlier report with [125I]HCG eluted from rat testis, no enhancement of binding of the eluted [125I]HCG was observed with fresh tissue. These results could be explained by the extraction of non-dialyzable intracellular component during the [125I]HCG elution procedure from the luteoma homogenate which combines with HCG to lower its binding and alter its electrophoretic mobility. This component could be extracted from other mouse tissues and combines with other labelled peptide hormones. Data in the present report support in part the hypothesis that gonadotrophins eluted from mouse luteoma and human corpus luteum are not altered by their interaction with tissue receptors.

Corpus luteum and endometrial function in ewes post partum: a study in vivo and in vitro

1992 ◽  
Vol 4 (1) ◽  
pp. 77 ◽  
Author(s):  
JM Wallace ◽  
CJ Ashworth ◽  
RP Aitken ◽  
MA Cheyne
Keyword(s):  
Corpus Luteum ◽  
Post Partum ◽  
Polyacrylamide Gel Electrophoresis ◽  
Uterine Horn ◽  
Corpora Lutea ◽  
Luteal Function ◽  
Progesterone Production ◽  
Release Device

Induction of ovulation post partum is associated with a high incidence of prematurely regressing corpora lutea. However, inadequate luteal function is not the sole reason for pregnancy failure, because ewes with normal corpus luteum function and successful fertilization also fail to establish pregnancies. The effects of suckling status and the interval from post partum to rebreeding on corpus luteum and endometrial function were examined in vivo and in vitro. Ewes were weaned early or allowed to lactate, induced to ovulate using a progesterone-impregnated controlled internal drug release device and an intramuscular injection of pregnant mare serum gonadotrophin, and inseminated (intrauterine) at either 21 or 35 days post partum (n = 10 per group). A further 10 standard ewes whose interval from parturition was in excess of 150 days were included for comparative purposes. On Day 10 after insemination the pregnancy rate was determined in four ewes from each of the post-partum groups and five standard ewes. These ewes were then ovariectomized and hysterectomized for studies in vitro. The incidence of premature luteal regression, as assessed by progesterone concentrations in peripheral blood was independent of the suckling stimulus but dependent on stage post partum (21 days post partum, 6 of 19 ewes; 35 days post partum, 0 of 19 ewes; P less than 0.05). Luteal function was normal in all standard ewes. Ovulation rate, corpus luteum weight, corpus luteum progesterone content and basal progesterone production in vitro were significantly less in 21-day than in 35-day post-partum ewes. Pregnancy rates as determined on Day 10 or at term were low in all post-partum groups (7 out of the 38 ewes inseminated) compared with standard ewes (8 of 10). Uterine function was assessed by culturing endometrial tissue from the tip and body of each uterine horn in the presence of [3H]leucine for 30 h at 37 degrees C. Incorporation of radiolabel into non-dialysable proteins synthesized and secreted by the endometrium in vitro was independent of uterine horn location and suckling status but was significantly lower (P less than 0.001) in media from 21-day than from 35-day post-partum ewes. Irrespective of treatment group, incorporation of radiolabel was positively correlated with mean plasma progesterone concentrations on Days 2-10 after insemination and with basal progesterone production in vitro. Secreted proteins were detected by two-dimensional-polyacrylamide-gel electrophoresis and fluorography.(ABSTRACT TRUNCATED AT 400 WORDS)

Monoclonal antibody recognition of estrogen receptor in rabbit corpus luteum

1983 ◽  
Vol 244 (5) ◽  
pp. E494-E498
Author(s):  
J. A. Holt ◽  
M. A. Lorincz ◽  
W. J. King
Keyword(s):  
Monoclonal Antibody ◽  
Estrogen Receptor ◽  
Corpus Luteum ◽  
High Salt ◽  
Corpora Lutea ◽  
Nuclear Fraction ◽  
Human Breast ◽  
Nuclear Extracts ◽  
Binding Component

We demonstrated previously by administering [3H]estradiol and using autoradiography that, in vivo, the exogenous estradiol that will sustain progesterone production is sequestered to nuclei of the luteal cells in corpora lutea of pseudopregnant rabbits. Our objective in the present experiments was to use an immunological method to demonstrate that estrogen receptor of the rabbit corpus luteum is associated with this uptake. For this purpose, we prepared nuclear extracts from corpora lutea removed from anesthetized pseudopregnant rabbits 10 min after arterial infusion of 125I-estradiol. These extracts were then analyzed by sucrose density gradient centrifugation in the presence and absence of monoclonal antibody against human breast cancer estrogen receptor. We found that the 125I-estradiol-binding component extracted with 0.5 M KCl from the nuclear pellet sediments in the 3-4S region in high-salt gradients; in the presence of monoclonal antibody (D-547 Sp2 gamma), the entire estradiol-binding component is shifted to the 8-9S region, indicating the formation of immunocomplex with the 125I-estradiol-receptor moiety. The principal estradiol-binding component that can be observed in the 3-4S region of high-salt gradients of cytosol of rabbit corpora lutea reacts with this antibody regardless of whether 125I- or [3H]estradiol is given in vivo or in vitro. In both cytosol and nuclear extracts of luteal tissue, unlabeled diethylstibestrol totally inhibits the binding of radiolabeled estrogen to this antibody-shifted 125I- or [3H]estradiol-binding moiety; neither progesterone nor testosterone inhibit binding of radiolabeled estrogen to the antibody-shifted moiety. From these findings we conclude that sequestering of estradiol by the rabbit corpus luteum in vivo is accomplished by the steroid-specific estrogen receptor that shares characteristics of the estrogen receptor found in human breast cancers, including a) antigenic features and b) the capacity to translocate estrogens from the cytosol to the nuclear fraction.

scholarly journals Morphology and vascularization of the corpus luteum of peccaries (Pecari tajacu, Linnaeus, 1758) throughout the estrous cycle

2016 ◽  
Vol 68 (1) ◽  
pp. 87-96 ◽  
Author(s):  
M.T.M. Miranda-Moura ◽  
G.B. Oliveira ◽  
G.C.X. Peixoto ◽  
J.M. Pessoa ◽  
P.C. Papa ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Estrous Cycle ◽  
Functional Activity ◽  
Secretory Activity ◽  
Cycle Phase ◽  
Vascular Density ◽  
Corpora Lutea ◽  
Estrus Synchronization ◽  
Progesterone Synthesis ◽  
Pecari Tajacu

The current paper characterizes the changes in morphology and vascularization of the corpus luteum of collared peccaries during the estrous cycle and correlates progesterone synthesis (P4). Twenty females were subjected to a treatment for estrus synchronization; an ear implant containing 1.5 mg of norgestomet was implanted on D0, whereas on D9 the peccaries received an IM injection of eCG 200UI and 50g of PGF2a. The animals were divided into four groups (G1, G2, G3 and G4) and euthanized on post-ovulation days 3, 12, 18 and 22. The ovaries were collected and the corpora lutea were measured and processed for histological and vascular density (Dv). Blood was collected for dosage of P4 serum. The morphology of the ovaries, the corpora lutea and P4 varied significantly during the estrous cycle (P<0.001). There was a significant co-relationship between weight and length of the ovaries and CL (r = 0.66, r = 0.52, P<0.05, respectively) and between weight, length and width of the CL and P4 (r = 0.51, r = 0.54 and r = 0.68, P<0.05, respectively). The luteal Dv was highly influenced by the estrous cycle phase (P<0.0001). The P4 and luteal Dv concentrations were higher in G2 and evidenced maximum secretory activity, with a highly significant correlation (P<0.0001). Assessed lutein parameters may estimate the phase of the estrous cycle in peccaries and the functional activity of the corpus luteum.

THE ENTRY OF ASCORBIC ACID INTO THE CORPUS LUTEUM IN VIVO AND IN VITRO AND THE EFFECT OF LUTEINIZING HORMONE

1967 ◽  
Vol 39 (1) ◽  
pp. 27-35 ◽  
Author(s):  
D. A. STANSFIELD ◽  
A. P. FLINT
Keyword(s):  
Ascorbic Acid ◽  
Exchange Rate ◽  
Luteinizing Hormone ◽  
Corpus Luteum ◽  
Plasma Ascorbic Acid ◽  
Progesterone Synthesis ◽  
Rat Ovary ◽  
Energy Dependent

SUMMARY Judged from the exchange rate between luteal and plasma ascorbic acid there appears to be no compartmentalization of ascorbic acid within the corpus luteum. Evidence is presented to show that the uptake of ascorbic acid into slices of superovulated rat ovary is an energy-dependent process which is inhibited by luteinizing hormone (LH) by means of its stimulatory effect on progesterone synthesis. The results are discussed in relation to the adrenal cortex and methods involving ascorbic acid depletion used in the assay of corticotrophin and LH.

Local production of progesterone by the corpus luteum of the marmoset monkey in response to perfusion with chorionic gonadotrophin and melatonin in vivo

1987 ◽  
Vol 112 (3) ◽  
pp. 449-457 ◽  
Author(s):  
G. E. Webley ◽  
J. P. Hearn
Keyword(s):  
Corpus Luteum ◽  
Positive Control ◽  
Chorionic Gonadotrophin ◽  
Test Material ◽  
Corpora Lutea ◽  
Local Production ◽  
Progesterone Secretion ◽  
Stimulation Of

ABSTRACT The effect of human chorionic gonadotrophin (hCG) and melatonin on the local production of progesterone by the marmoset corpus luteum was investigated in vivo using a perfusion cannula system. Progesterone secretion was measured in 10-min fractions of buffer which had been perfused through the corpus luteum at a flow rate of 70 μl/min for a maximum of 3 h in anaesthetized animals. Two corpora lutea were cannulated in each animal; one for perfusion of test material and the other for perfusion with buffer alone as a control. Perfusion with hCG (25 i.u./ml), investigated as a positive control, produced a marked stimulation of progesterone secretion which increased 10–20 min from the start of perfusion and reached a peak after 30–60 min. A stimulation of progesterone was also observed after perfusion with melatonin (860 pmol/l). The response was evident within 10–30 min of the hormone reaching the corpus luteum and was similar in magnitude to that observed for hCG. The ability of melatonin to stimulate progesterone secretion supports previous in-vitro studies and suggests an ovarian action for melatonin in the primate. The local perfusion system described may have potential uses in studies of luteal function related to aspects of infertility or regulation of fertility. J. Endocr. (1987) 112, 449–457

scholarly journals Neuromediator bioamines in the histogenesis of corpora lutea

1994 ◽  
Vol 40 (5) ◽  
pp. 44-46
Author(s):  
Yu. V. Pogorelov ◽  
S. V. Dindyayev
Keyword(s):  
Corpus Luteum ◽  
Histochemical Method ◽  
Corpora Lutea ◽  
Progesterone Synthesis

The role of neuromediator bioamines in histogenesis of corpora lutea was under study. Cryostate slices of ovaries from 27 cats were treated after A. Bjorklunds fluorescent histochemical method modified by V. N. Shvalev and N. I. Zhuchkova. The content of serotonin and catecholamines was measured cytospectrofluorometrically in varicose dilatations and intervari- cose sites о perivascular plexuses and terminals, in membranous and parenchymatous macrophages of corpus luteum. A reliably increased content of the examined neuromediators was found in all the tested nervous structures at the stage of glandular metamorphosis and corpus luteum maturity. Serotonin and catecholamines are believed to be needed for glandular metamorphosis and corpus luteum maturation. A higher level of catecholamines at the stage of corpora lutea maturity in comparison with serotonin may be explained by an activating effect of these neuromediators on progesterone synthesis. Catecholamines may be necessary for luteolythic action of prostaglandines. Macrophages seem to inactivate mediator excess.

Regulation of the corpus luteum of early pregnancy in the marmoset monkey: local interactions of luteotrophic and luteolytic hormones in vivo and their effects on the secretion of progesterone

1987 ◽  
Vol 114 (2) ◽  
pp. 231-239 ◽  
Author(s):  
J. P. Hearn ◽  
G. E. Webley
Keyword(s):  
Corpus Luteum ◽  
Early Pregnancy ◽  
Local Level ◽  
Corpora Lutea ◽  
Progesterone Production ◽  
Marmoset Monkey ◽  
Progesterone Secretion ◽  
Late Luteal Phase ◽  
Prostaglandin F

ABSTRACT The interaction between luteotrophic and luteolytic agents in controlling progesterone production by the marmoset corpus luteum in the late luteal phase/early pregnancy was investigated at the local level in vivo using a perfusion cannula system. Perfusion of the prostaglandin F2α(PGF2α) analogue, cloprostenol (0·5 μg/ml), resulted in an immediate fall in progesterone production. This response was not sustained in two out of five corpora lutea but pregnancy was terminated in all animals exposed to PGF2α. Perfusion of human chorionic gonadotrophin (hCG) (4 μg/ml) alone significantly stimulated progesterone secretion but there was no response to hCG when the corpus luteum had previously been perfused with PGF2α. Perfusion with hCG together with PGF2α prevented a fall in progesterone secretion. The results suggest that the luteolytic action of PGF2α in the marmoset may be to prevent luteotrophic support of the corpus luteum. Melatonin (860 pmol/l), perfused either with PGF2α or after PGF2α, stimulated progesterone production. The ability of melatonin to influence progesterone production by the primate corpus luteum may therefore be by both a direct luteotrophic action and the prevention of luteolysis. Application of the perfusion system in order to investigate the ability of deglycosylated hCG to antagonize the action of hCG at the corpus luteum showed the necessity of testing pure preparations of hormones. J. Endocr. (1987) 114, 231–239

Über die Effektivität von DL- im Vergleich zu D-Cloprostenol bei Milchrindern mit einem Corpus luteum periodicum oder Corpus luteum persistens

2005 ◽  
Vol 33 (06) ◽  
pp. 395-403 ◽  
Author(s):  
M. Thumes ◽  
M. Holsteg ◽  
K. Failing ◽  
H. Bostedt ◽  
R. Hospes
Keyword(s):  
Corpus Luteum ◽  
Corpora Lutea ◽  
Klinische Relevanz

Zusammenfassung Ziel der Untersuchung: Überprüfung der Wirksamkeit von DL-Cloprostenol vs. D-Cloprostenol in der Östrusinduktion bei Milchrindern. Probanden und Methoden: Das Probandenkollektiv umfasste 134 Rinder im Durchschnittsalter von 4,0 ± 0,5 Jahren (99 in Laktation, 35 Färsen). Vor alternierender Injektion zweier Cloprostenolpräparate (Gruppe A: DL-Cloprostenol, 500 μg, n = 70; Gruppe B: D-Cloprostenol, 150 μg, n = 64) wurde die Progesteronkonzentration im Serum bestimmt. Gynäkologische Kontrollen erfolgten 0–3 d post injectionem (p. inj.), wobei die als inseminationsfähig beurteilten Probanden (n = 123) am dritten Tag besamt wurden. Ergebnisse: In beiden Gruppen kam es bis zum dritten Tag p. inj. zu einer deutlichen Konsistenzänderung oder Regression der Corpora lutea (p ≤ 0,001). Die Lysis eines C. l. periodicum verlief bei Kühen markanter als bei Färsen (p ≤ 0,017). Insgesamt war D-Cloprostenol dem DL-Cloprostenol hier leicht überlegen. Am dritten Tag p. inj. wiesen 67,1% (A) bzw. 71,9% (B) der Probanden gut ausgeprägte Östrusanzeichen auf. Als inseminationsfähig wurden 94,3% (A) und 89,1% (B) der Tiere eingestuft. Ein geringer Präparateunterschied bestand hinsichtlich des Graviditätsresultates. Bei einem C. l. persistens verlief die Regression weniger progressiv als bei einem C. l. periodicum (p ≤ 0,024). Signifikante Wechselwirkungen zwischen den Einflussfaktoren Präparat und Indikation einerseits sowie für die übrigen gynäkologischen Kriterien andererseits ergaben sich nicht. Bei den Probanden mit prostaglandininduziertem Zyklus nach einem C. l. persistens lag die Graviditätsrate nach der 1. KB deutlich niedriger (31,9%) als bei Tieren nach Lysis eines C. l. periodicum (52,4%, p = 0,08). Schlussfolgerungen und klinische Relevanz: Der Einsatz von D-Cloprostenol erbringt im Wesentlichen die Resultate wie der von DL-Cloprostenol. Eine Überlegenheit konnte jedoch für die Progressivität der lytischen Wirkung des D-Cloprostenols festgestellt werden. Kühe mit C. l. persistens reagierten präparateunabhängig weniger intensiv als solche mit C. l. periodicum.

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