INTERCONVERSION OF PROGESTERONE AND 20α-DIHYDROPROGESTERONE AND OF ANDROSTENEDIONE AND TESTOSTERONE IN VITRO BY BLOOD AND ERYTHROCYTES

1968 ◽  
Vol 58 (3) ◽  
pp. 419-444 ◽  
Author(s):  
H. J. van der Molen ◽  
D. Groen
Keyword(s):  
Dehydrogenase Activity ◽  
Venous Blood ◽  
Hydroxysteroid Dehydrogenase ◽  
Linear Increase ◽  
Equivalent Amount ◽  
Men And Women ◽  
Peripheral Venous Blood ◽  
Normal Men

ABSTRACT Peripheral venous blood and erythrocytes from normal men and women, as well as from dogs, rabbits and sheep were incubated with 14C-labeled progesterone*, 20α-dihydroprogesterone, androstenedione and testosterone. The presence in blood and erythrocytes of a 20α-hydroxysteroid dehydrogenase activity, catalyzing the interconversion progesterone ⇄ 20α-dihydroprogesterone, and of a 17β-hydroxysteroid dehydrogenase activity, catalyzing the interconversion androstenedione ⇆ testosterone was observed. Incubation with washed erythrocytes in the presence of glucose and several co-factors favoured the formation of the reduced compounds: 20α-dihydroprogesterone or testosterone. Incubations with washed erythrocytes, without addition of glucose and co-factors, favoured the formation of the oxidized compounds: progesterone and androstenedione. Incubation of steroids with whole blood, resulted in metabolism of progesterone to 20α-dihydroprogesterone and of androstenedione to testosterone. The formation of the product during incubation in vitro increased linearly with time of incubation (15—180 min). Incubations of 20 ml blood or the equivalent amount of erythrocytes with substrate amounts of steroids varying from 0.5 to 3000 μg, gave a linear increase in the amount of product formed. The possible significance of these observations in vitro for steroid metabolism in vivo is discussed.

FORMATION OF EPITESTOSTERONE BY HUMAN BLOOD AND ADRENAL TISSUE

1967 ◽  
Vol 54 (2) ◽  
pp. 208-214 ◽  
Author(s):  
Jorge Blaquier ◽  
Ralph I. Dorfman ◽  
Enrico Forchielli
Keyword(s):  
Venous Blood ◽  
Endocrine Gland ◽  
Men And Women ◽  
Peripheral Venous Blood ◽  
Adrenal Tissue ◽  
Idiopathic Hirsutism ◽  
Normal Human ◽  
Normal Men ◽  
Peripheral Production

ABSTRACT Whole peripheral venous blood from normal men and women, and from females with idiopathic hirsutism was incubated in vitro with labelled testosterone, androstenedione and dehydroepiandrosterone. Epitestosterone was formed consistently from added testosterone, in some cases from androstenedione but not from dehydroepiandrosterone. The rate of formation of epitestosterone from testosterone by blood of normal men and women is similar, whereas the rate of formation in blood from female idiopathic hirsutes was several fold greater. In a similar manner, normal human adrenal tissue also formed epitestosterone from added testosterone but not from androstenedione nor dehydroepiandrosterone. These results suggest that the origin of urinary epitestosterone can be the resultant of both peripheral production and endocrine gland secretion.

ETUDES IN VIVO. SUR LE METABOLISME DES ANDROGENES APRES ADMINISTRATION DE STEROIDES INHIBITEURS DE L'OVULATION

1966 ◽  
Vol 53 (1) ◽  
pp. 37-52 ◽  
Author(s):  
Pierre Mauvais-Jarvis
Keyword(s):  
Dehydrogenase Activity ◽  
Metabolic Pathway ◽  
Urinary Metabolites ◽  
Hydroxysteroid Dehydrogenase ◽  
Before And After ◽  
Normal Men ◽  
Ethinyl Oestradiol

ABSTRACT Radioactive dehydroepiandrosterone sulfate and testosterone, which are two circulating compounds in humans, have been injected into normal men, women and patients with Stein-Leventhal syndrome. These injections were made before and after administration of ethinyl-oestradiol, lynoestrenol and association of lynoestrenol and mestranol (Lyndiol®). The per cent conversion of injected steroids into 17-ketonic and 17β-hydroxylated urinary metabolites was calculated. The results observed can be summarized as follows: in all cases, the yields of sulfate metabolites formed from radioactive precursors were more important after treatment by antiovulatory steroids, especially urinary dehydroepiandrosterone sulfate derived from injected dehydroepiandrosterone sulfate: aetiocholanolone and androsterone formed from testosterone. The modifications in the 5β/5α ratio of androstanediols suggest that oral synthetic oestrogens and progestins inhibit the 5α-Δ4 reductase implicated in the »17β-hydroxyl metabolic pathway« of testosterone. A change in 17β-hydroxysteroid dehydrogenase activity is also postulated, because testosterone was more metabolized into androsterone via androstenedione, and less reduced into androstanediol after antiovulatory steroids.

FUNCTIONAL LUTEOLYSIS IN THE PSEUDOPREGNANT RAT: EFFECTS OF PROSTAGLANDIN F2α AND 16-ARYLOXY PROSTAGLANDIN F2α IN VITRO

1979 ◽  
Vol 81 (1) ◽  
pp. 157-165 ◽  
Author(s):  
A. K. HALL ◽  
J. ROBINSON
Keyword(s):  
Dehydrogenase Activity ◽  
Dose Range ◽  
Prostaglandin F2α ◽  
Hydroxysteroid Dehydrogenase ◽  
In Vitro System ◽  
Maximum Inhibition ◽  
Incubation Periods ◽  
Relative Potencies

The present work concerns the luteolytic effects of prostaglandin (PG) F2α and its analogue, 16-aryloxy PGF2α, upon isolated luteal cells. Varying doses of these two prostaglandins were incubated with cells in the presence or absence of an optimum stimulatory dose of LH (1 μg/ml). The total contents of progesterone and 20α-dihydroprogesterone in flasks were determined after the incubation periods by radioimmunoassay. Both prostaglandins inhibited basal synthesis of progesterone and 20α-dihydroprogesterone, maximum inhibition occurring at concentrations of either PG of between 250 and 500 ng/ml. In this dose range both prostaglandins were found to abolish LH-stimulated progestogen synthesis completely. These effects were discernible within 5 min of incubation. The studies demonstrated that the onset of PG-induced luteolysis in vitro is characterized by an inhibition of the biosynthesis of both progesterone and its weakly progestogenic metabolite, 20α-dihydroprogesterone; induction of 20α-hydroxysteroid dehydrogenase activity by either PG was not found in incubations extending up to 60 min. In contrast to their relative potencies in vivo, PGF2α and 16-aryloxy PGF2α were essentially equipotent in this in-vitro system.

The procoagulant effects of factor V Leiden may be balanced against decreased levels of factor V and do not reflect in vivo thrombin formation in newborns

2006 ◽  
Vol 95 (03) ◽  
pp. 434-440 ◽  
Author(s):  
Satu Hyytiäinen ◽  
Ulla Wartiovaara-Kautto ◽  
Veli-Matti Ulander ◽  
Risto Kaaja ◽  
Markku Heikinheimo ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Platelet Rich Plasma ◽  
Venous Blood ◽  
Factor V Leiden ◽  
Factor V ◽  
Cord Plasma ◽  
Adult Plasma ◽  
Thrombin Formation

SummaryThrombin regulation in newborns remains incompletely understood.We studied tissue factor-initiated thrombin formation in cord plasma in vitro, and the effects of Factor VLeiden (FVL) heterozygosity on thrombin regulation both in vitro and in vivo in newborns. Pregnant women with known thrombophilia (n=27) were enrolled in the study. Cord blood and venous blood at the age of 14 days were collected from 11 FVL heterozygous newborns (FVL-positive) and from 16 FVL-negative newborns. Prothrombin fragment F1+2 and coagulation factors were measured. Tissue factor-initiated thrombin formation was studied in cord platelet-poor plasma (PPP) of FVL-negative and -positive newborns, and in both PPP and platelet-rich plasma (PRP) of healthy controls. The endogenous thrombin potential (ETP) in cord PPP or PRP was ∼60% of that in adult plasma, while thrombin formation started ∼55% and ∼40% earlier in cord PPP and PRP, respectively. Further, in FVL-positive newborns thrombin formation started significantly earlier than in FVL-negative newborns. Exogenous activated protein C (APC) decreased ETP significantly more in cord than in adult PRP. In FVL-negative cord plasma 5nM APC decreased ETP by 17.4±3.5% (mean±SEM) compared with only 3.5±3.8% in FVL-positive cord plasma (p=0.01). FVL-positive newborns showed similar levels of F1+2 but significantly decreased levels of factor V compared with FVL negative newborns both in cord plasma (FV 0.82±0.07 U/ml vs. 0.98±0.05 U/ml, p=0.03) and at the age of two weeks (FV 1.15±0.04 U/ml vs. 1.32±0.05 U/ml, p=0.03). In conclusion, newborn plasma showed more rapid thrombin formation and enhanced sensitivity to APC compared with adult plasma. FVL conveyed APC resistance and a procoagulant effect in newborn plasma. Lack of elevated F1+2 levels in FVL-positive infants, however, suggested the existence of balancing mechanisms; one could be the observed lower level of factor V in FVL heterozygous newborns.

scholarly journals Prolactin and Male Fertility: The Long and Short Feedback Regulation

2009 ◽  
Vol 2009 ◽  
pp. 1-13 ◽  
Author(s):  
M. K. Gill-Sharma
Keyword(s):  
Chromatin Condensation ◽  
Feedback Regulation ◽  
Pituitary Hormones ◽  
Feedback Mechanism ◽  
Reproductive Hormones ◽  
Male Rats ◽  
Normal Men

In the last 20 years, a pituitary-hypothalamus tissue culture system with intact neural and portal connections has been developed in our lab and used to understand the feedback mechanisms that regulate the secretions of adenohypophyseal hormones and fertility of male rats. In the last decade, several in vivo rat models have also been developed in our lab with a view to substantiate the in vitro findings, in order to delineate the role of pituitary hormones in the regulation of fertility of male rats. These studies have relied on both surgical and pharmacological interventions to modulate the secretions of gonadotropins and testosterone. The interrelationship between the circadian release of reproductive hormones has also been ascertained in normal men. Our studies suggest that testosterone regulates the secretion of prolactin through a long feedback mechanism, which appears to have been conserved from rats to humans. These studies have filled in a major lacuna pertaining to the role of prolactin in male reproductive physiology by demonstrating the interdependence between testosterone and prolactin. Systemic levels of prolactin play a deterministic role in the mechanism of chromatin condensation during spermiogenesis.

'Liver-type' 11β-hydroxysteroid dehydrogenase cDNA encodes reductase but not dehydrogenase activity in intact mammalian COS-7 cells

1994 ◽  
Vol 13 (2) ◽  
pp. 167-174 ◽  
Author(s):  
S C Low ◽  
K E Chapman ◽  
C R W Edwards ◽  
J R Seckl
Keyword(s):  
Dehydrogenase Activity ◽  
Rat Liver ◽  
Mammalian Cells ◽  
Reductase Activity ◽  
Hydroxysteroid Dehydrogenase ◽  
Luciferase Reporter ◽  
Luciferase Expression ◽  
Intact Cells ◽  
Mmtv Ltr

ABSTRACT 11β-Hydroxysteroid dehydrogenase (11β-HSD) catalyses the metabolism of corticosterone to inert 11-dehydrocorticosterone, thus preventing glucocorticoid access to otherwise non-selective renal mineralocorticoid receptors (MRs), producing aldosterone selectivity in vivo. At least two isoforms of 11β-HSD exist. One isoform (11β-HSD1) has been purified from rat liver and an encoding cDNA cloned from a rat liver library. Transfection of rat 11β-HSD1 cDNA into amphibian cells with a mineralocorticoid phenotype encodes 11 β-reductase activity (activation of inert 11-dehydrocorticosterone) suggesting that 11β-HSD1 does not have the necessary properties to protect renal MRs from exposure to glucocorticoids. This function is likely to reside in a second 11β-HSD isoform. 11β-HSD1 is co-localized with glucocorticoid receptors (GRs) and may modulate glucocorticoid access to this receptor type. To examine the predominant direction of 11β-HSD1 activity in intact mammalian cells, and the possible role of 11β-HSD in regulating glucocorticoid access to GRs, we transfected rat 11β-HSD1 cDNA into a mammalian kidney-derived cell system (COS-7) which has little endogenous 11β-HSD activity or mRNA expression. Homogenates of COS-7 cells transfected with increasing amounts of 11β-HSD cDNA exhibited a dose-related increase in 11 β-dehydrogenase activity. In contrast, intact cells did not convert corticosterone to 11-dehydrocorticosterone over 24 h, but showed a clear dose-related 11β-reductase activity, apparent within 4 h of addition of 11-dehydrocorticosterone to the medium. To demonstrate that this reflected a change in functional intracellular glucocorticoids, COS-7 cells were co-transfected with an expression vector encoding GR and a glucocorticoid-inducible MMTV-LTR luciferase reporter construct, with or without 11β-HSD. Corticosterone induced MMTV-LTR luciferase expression in the presence or absence of 11β-HSD. 11-Dehydrocorticosterone was without activity in the absence of 11β-HSD, but induced MMTV-LTR luciferase activity in the presence of 11β-HSD. These results indicate that rat 11β-HSD1 can behave exclusively as a reductase in intact mammalian cells. Thus in some tissues in vivo, 11β-HSD1 may regulate ligand access to GRs by reactivating inert glucocorticoids.

Age-dependent changes in volume and haemoglobin content of erythrocytes in the carp (Cyprinus carpio L.)

1989 ◽  
Vol 141 (1) ◽  
pp. 133-149 ◽  
Author(s):  
W. Speckner ◽  
J. F. Schindler ◽  
C. Albers
Keyword(s):  
Gel Filtration ◽  
Linear Increase ◽  
Human Erythrocytes ◽  
Main Peak ◽  
Red Cell ◽  
Human Haemoglobin ◽  
Cell Fractions ◽  
Haemoglobin Content

Carp erythrocytes were fractionated by angle-head centrifugation which yielded fractions with a linear increase in density. Haematological examinations revealed that the heavier red blood cells of carp had greater volumes (MCV), more haemoglobin (MCH) and higher haemoglobin concentrations (MCHC) than light ones. The same experiments with human red cell fractions yielded a decrease in MCV, constant MCH and an increase in MCHC. Haemoglobin content in individual erythrocytes was also determined by scanning stage absorbance cytophotometry to establish the frequency distribution of the cellular haemoglobin contents. In carp, the distribution was symmetrical with the means increasing with density. No such change with cell density was found in human erythrocytes. Both carp and human erythrocytes incorporated [2-14C]glycine in vitro. After gel filtration, radioactivity was detected in carp, but not in human, haemoglobin fractions. 14C was found in all three haemoglobin fractions, obtained by isoelectric focusing, and was present in the haem and in the globin. [2-14C]glycine-labelled erythrocytes were reinjected into chronically cannulated carp and followed in vivo for several months. With time, the main peak of scintillation counts shifted from red cell fractions of low to high density. This is considered as evidence that density and age of red cells in carp are positively correlated and that erythrocytes can synthesize haemoglobin while circulating in the peripheral blood.

scholarly journals Investigation of the In Vitro and In Vivo efficiency of RM-532-105, a 17β-hydroxysteroid dehydrogenase type 3 inhibitor, in LAPC-4 prostate cancer cell and tumor models

PLoS ONE ◽  
2017 ◽  
Vol 12 (2) ◽  
pp. e0171871 ◽  
Author(s):  
Lucie Carolle Kenmogne ◽  
Jenny Roy ◽  
René Maltais ◽  
Mélanie Rouleau ◽  
Bertrand Neveu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Hydroxysteroid Dehydrogenase ◽  
Tumor Models ◽  
Type 3

HYPOTHALAMIC, PITUITARY AND TESTICULAR FUNCTION DURING SEXUAL MATURATION OF THE MALE RAT

1977 ◽  
Vol 72 (1) ◽  
pp. 17-26 ◽  
Author(s):  
A. H. PAYNE ◽  
R. P. KELCH ◽  
E. P. MURONO ◽  
J. T. KERLAN
Keyword(s):  
Dehydrogenase Activity ◽  
Sexual Maturation ◽  
Hydroxysteroid Dehydrogenase ◽  
Male Rat ◽  
Releasing Hormone ◽  
Isomerase Activity ◽  
Serum Lh ◽  
Rate Of Increase ◽  
Gonadotrophin Releasing Hormone

SUMMARY Hypothalamic content of gonadotrophin-releasing hormone (GnRH), serum LH and FSH, capacity of the testis to synthesize testosterone in vitro, and testicular 5-ene-3β-hydroxysteroid dehydrogenase-isomerase and 17β-hydroxysteroid dehydrogenase were measured in groups of rats at approximately 5 day intervals from birth to day 64 and at days 74 and 89. The capacity of the testes to synthesize testosterone in vitro was measured in the presence of a saturating dose of rat LH. Gonadotrophin-releasing hormone increased steadily from 0·17 ng per hypothalamus at birth to a maximum of 7 ng at day 52 and then remained constant. LH concentrations were highly variable and often exceeded adult values between days 10 and 32. After day 32 a steady rise was observed which reached adult values between days 37 and 42. FSH concentrations markedly increased from 255 ng/ml observed at birth and day 10 to a peak value of 1000 ng/ml at day 32. Subsequently there was a steady decline in FSH values until day 74 when the concentration returned to values found at birth. 5-ene-3β-Hydroxysteroid dehydrogenase-isomerase activity exhibited a rapid increase between days 12 and 19 followed by an even greater rate of increase between days 19 and 32 when adult levels were attained. 17β-Hydroxysteroid dehydrogenase activity was very low between birth and day 22. Enzyme activity began to increase at day 22 with a rapid increase in activity observed between days 37 and 58. The increase in capacity to synthesize testosterone closely followed the increase in 17β-hydroxysteroid dehydrogenase activity. The study demonstrates that during sexual maturation in the male rat, changes in serum LH and FSH do not reflect changes in hypothalamic GnRH. The appearance of Leydig cells as monitored by 5-ene-3β-hydroxysteroid dehydrogenase-isomerase activity precedes by approximately 20 days the increase in testicular capacity to synthesize testosterone in vitro. The latter coincides with the increase in 17β-hydroxysteroid dehydrogenase activity. These results suggest that 17β-hydroxysteroid dehydrogenase is a limiting factor in the ability of the testis to respond to LH stimulation.

Sign in / Sign up

Export Citation Format

Share Document