METABOLISM OF 20β-HYDROXY-4-PREGNEN-3-ONE IN UTERINE TISSUE OF NON-PREGNANT RATS IN VITRO

ABSTRACT In vitro experiments carried out with uterus preparations of ovariectomized adult rats indicate the presence in this tissue of a 20β-hydroxysteroid-oxidoreductase which catalyzes the conversion of 20β-hydroxy-4-pregnen-3-one to progesterone. Since a hepatic 20β-hydroxysteroid-oxidoreductase is absent in adult female rats, the myometrial enzyme can be responsible for the biological activity of 20β-hydroxy-4-pregnen-3-one in these animals. Besides progesterone five metabolites were isolated and identified after incubation of [4-14C]20β-hydroxy-4-pregnen-3-one with uterine tissue: 20β-hydroxy-5α-pregnan-3-one, 20β-hydroxy-5β-pregnan-3-one, 5α-pregnane-3α,20β-diol, 4-pregnene-3α,20β-diol and 4-pregnene-3β,20β-diol. The conversion of 20β-hydroxy-4-pregnen-3-one to progesterone permits us to regard all five steroids isolated as progesterone metabolites in the rat uterus. 20β-hydroxy-5β-pregnan-3-one is the first C21-metabolite with a 5β(H)-configuration isolated in the rat uterus, which indicates the presence of 5β-reductase in this tissue.

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METABOLISM OF PROGESTERONE IN UTERINE TISSUE OF NON-PREGNANT RATS IN VITRO

Acta Endocrinologica ◽

10.1530/acta.0.0830583 ◽

1976 ◽

Vol 83 (3) ◽

pp. 583-603 ◽

Cited By ~ 2

Author(s):

B. P. Lisboa ◽

M. Holtermann

Keyword(s):

Quantitative Difference ◽

Total Activity ◽

Allylic Alcohols ◽

Uterine Tissue ◽

Oxidoreductase Activity ◽

Pregnant Rats ◽

Progesterone Metabolites ◽

Influence Of Substrate ◽

First Time

ABSTRACT The metabolism of labelled progesterone was studied in vitro in uterine tissue of non-pregnant rats with particular emphasis on the influence of substrate concentration. Neither a qualitative nor quantitative difference was found for a steroid tissue ratio between 15 × 10−6 and 4.2 × 10−9 to 1 g (substrate amounts between 57.73 and 0.02 nmol); with both concentrations 42 to 44 per cent of progesterone was metabolized to about 35 per cent monohydroxymonoketonic steroids and 4–6 per cent dihydroxylated C21O2-compounds. In both sets of incubations we have isolated and identified the following steroids: 3α-hydroxy-5α-pregnan-20-one, 3β-hydroxy-4-pregnen-20-one, 3α-hydroxy-4-pregnen-20-one, 20α-hydroxy-4-pregnen-3-one, 5α-pregnane-3α,20α-diol and 4-pregnene-3α,20α-diol. The most abundant metabolite formed in these incubations was 3α-hydroxy-4-pregnen-20-one -which corresponds to about 30 per cent of the total activity recovered. It is the first time that the presence of 20α-hydroxysteroid-oxidoreductase activity is definitely established in this type of tissue. The identification of three allylic alcohols as progesterone metabolites in the rat uterus confirms that Δ4-3-hydroxysteroids are important intermediates in the in vitro uterine metabolism of steroids.

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Altered vascular contractility in adult female rats with hypertension programmed by prenatal glucocorticoid exposure

Journal of Endocrinology ◽

10.1677/joe.1.06506 ◽

2006 ◽

Vol 188 (3) ◽

pp. 435-442 ◽

Cited By ~ 31

Author(s):

P W F Hadoke ◽

R S Lindsay ◽

J R Seckl ◽

B R Walker ◽

C J Kenyon

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Adult Female ◽

Vascular Function ◽

Mesenteric Arteries ◽

Female Rats ◽

Control Group ◽

Pregnant Rats ◽

Vascular Contractility

Excessive exposure to glucocorticoids during gestation reduces birth weight and induces permanent hypertension in adulthood. The mechanisms underlying this programmed elevation of blood pressure have not been established. We hypothesised that prenatal glucocorticoid exposure may lead to vascular dysfunction in adulthood. Pregnant rats received dexamethasone (Dex) (100 μg/kg, s.c.) or vehicle (control) daily throughout pregnancy. Blood pressure was elevated (students t-test, unpaired; P < 0.05) in adult female offspring (aged 12–16 weeks) of Dex-treated mothers (148.0 ± 3.6 mmHg, n=10) compared with the control group (138.0 ± 2.5 mmHg, n=8). Vascular responsiveness in aortae and mesenteric arteries was differentially affected by prenatal Dex: aortae were less responsive to angiotensin II, whereas mesenteric arteries were more responsive to norepinephrine, vasopressin and potassium (mesenteric arteries respond poorly to angiotensin II in vitro). Acetylcholine-mediated, endothelium-dependent relaxation was similar in both groups. Prenatal exposure to Dex had no effect on blood pressure or aldosterone response to acute (15 min, i.v.) infusion of angiotensin II (75 ng/kg per min). In contrast, chronic (2-week, s.c.) infusion of angiotensin II (100 ng/kg per min) produced a greater elevation (P < 0.05) of blood pressure in Dex-treated rats (150.0 ± 3.6 mmHg) than in controls (135.3 ± 5.4 mmHg), and aldosterone levels were higher in Dex-treated animals. There was no angiotensin II-induced medial hypertrophy/hyperplasia in mesenteric arteries from Dex-treated rats. These results indicate that vascular function is altered in a region-specific manner in rats with glucocorticoid-programmed hypertension. Despite a striking increase in mesenteric artery contraction in Dex-treated rats, in vivo studies suggest that abnormalities of the renin-angiotensin-aldosterone system, rather than enhanced vascular contractility, may be responsible for the elevation of blood pressure in these animals.

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CORTICOSTEROID-UMSATZ UND CORTICOSTEROID-PRODUKTION BEI RATTEN UNTER DER BEHANDLUNG MIT ANABOLEN STEROIDEN

Acta Endocrinologica ◽

10.1530/acta.0.0480263 ◽

1965 ◽

Vol 48 (2) ◽

pp. 263-271 ◽

Cited By ~ 8

Author(s):

Herbert Schriefers ◽

Gerlinde Scharlau ◽

Franzis Pohl

Keyword(s):

Production Rate ◽

Adult Female ◽

Anabolic Steroids ◽

Reduction Rate ◽

Female Rats ◽

Adrenal Weight ◽

Hydrogenase Activity ◽

Anabolic Effect ◽

Liver Slices

ABSTRACT After the administration of anabolic steroids to adult female rats in daily doses of 1 mg per animal for 14 days, the following parameters were investigated: the rate of the Δ4-5α-hydrogenase-catalyzed cortisone reduction in liver slices and microsomal fractions, the adrenal weight and the in vitro corticosterone production rate. Among the steroids tested, only 17α-methyl-testosterone and 17α-ethyl-19-nor-testosterone were effective in lowering significantly cortisone reduction rate by liver slices with concomitant decreases in microsomal Δ4-5α-hydrogenase-activity. Testosterone, 19-nor-testosterone, 17α-ethinyl-19-nor-testosterone, 17α-methyl-17β-hydroxy-androsta-1,4-dien-3-one and 1-methyl-17β-hydroxy-androst-1-en-3-one were ineffective or only slightly effective. Adrenal weight and absolute corticosterone production rate (μg/60 min per animal) were decreased after treatment with 17α-methyl-testosterone, 17α-ethyl-19-nor-testosterone and 1-methyl-17β-hydroxy-androst-1-en-3-one. Corticosterone production was decreased with 17α-ethinyl-19-nor-testosterone in spite of an unchanged adrenal weight. The relative corticosterone production rate (μg/60 min · 100 mg adrenal) was in any cases unaffected. According to these results there exists – with the exception of 17α-ethinyl-19-nor-testosterone – a strict parallelism between corticosteroid turnover and corticosterone production rate: unchanged turnover is correlated with unchanged corticosterone production rate, while a decreased turnover is correlated with decreased adrenal activity. The protein-anabolic effect of certain anabolic steroids may be partly due to an anti-catabolic action of these compounds resulting from a decreased corticosteroid inactivation and production rate. Possible mechanisms by which anabolic steroids may affect corticosteroid-balance are discussed.

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Dissimilar Anxiety-like Behavior in Prepubertal and Young Adult Female Rats on Acute Exposure to Aluminium

Central Nervous System Agents in Medicinal Chemistry ◽

10.2174/1871524922666211231095507 ◽

2021 ◽

Vol 22 ◽

Author(s):

Trina Sengupta ◽

Sutirtha Ghosh ◽

Archana Gaur T. ◽

Prasunpriya Nayak

Keyword(s):

Body Weight ◽

Young Adult ◽

Adult Female ◽

Developmental Stages ◽

Elevated Plus Maze ◽

Age Groups ◽

Female Rats ◽

Acute Exposure ◽

Adult Rats ◽

Plus Maze

Background: Puberty is a developmental transition in which an estrogenic surge occurs, mediating the release of xenoestrogens, like aluminium. Aluminium’s effect on anxiety in rodents at the different developmental stages is inconsistent. Aims: This study aimed at investigating the effect of the metalloestrogenic property of aluminium on anxiety-like behavioral changes in prepubertal and young adult female rats. Objective: Considering this aim, our objective was to evaluate the anxiety-like behavior by the elevated plus maze in prepubertal and young adult female rats with or without acute exposure to aluminium. Methods: To address this property of aluminium, 5mg/Kg body weight (Al-5) and 10 mg/Kg body weight (Al-10) of aluminium was administered intraperitoneally to female rats at two developmental stages, prepubertal (PP; n = 8 for each dose) and young adult (YA; n = 6 for each dose) for two weeks. Post-treatment, three days behavioral assessment of the rats was done employing elevated plus maze. Results: Reduced escape latency was seen in Al-5, Al-10 pre-pubertal rats, and Al-5 young-adult rats on day 3. A significant reduction in open arm time was seen in the Al-5 young-adult rats. Aluminium treatment in the pre-pubertal rats reduced their head dipping and grooming. Reduced sniffing, head dipping, and stretch-attended posture in the treated young-adult female rats showed that they had impaired risk-taking tendency. Conclusion: Differential effect on the anxiety-like behavior in the pre-pubertal and young-adult female rats might be due to the metalloestrogenic property of aluminium, acting differently on the two age groups.

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Regrowth of atrophied skeletal muscle in adult rats after ending immobilization

Journal of Applied Physiology ◽

10.1152/jappl.1978.44.2.225 ◽

1978 ◽

Vol 44 (2) ◽

pp. 225-230 ◽

Cited By ~ 25

Author(s):

F. W. Booth

Keyword(s):

Skeletal Muscle ◽

Body Weight ◽

Adult Female ◽

Total Protein ◽

Recovery Time ◽

Time Course ◽

Citrate Synthase ◽

Female Rats ◽

Adult Rats ◽

Wet Weight

The recovery time course of muscle atrophied by immobilization was followed after removal of hindlimb casts from adult female rats. Increases of only 9% in body weight, 4% in gastrocnemius weight, and 10% in soleus weight occurred in controls during the 78-day duration of the experiment. There were no increases in the amounts of total protein or of citrate synthase activities in gastrocnemius or soleus during the first 3 days after removal of hindlimb casts; thereafter, there were increases in these paramters. Citrate synthase activities per mg of gastrocnemius protein were significantly higher at the 16th and 50th day of recovery. No significant differences for citrate synthase activity per mg of soleus occurred during recovery. Until the 50th day of recovery, no significant differences for total protein in soleus and for total protein and wet weight of gastrocnemius were observed between control and recovery values. However, the wet weight of the soleus returned rapidly during recovery and was not significantly different from control during recovery.

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Attenuated responses of muscle protein synthesis to fasting and insulin in adult female rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1992.262.1.e1 ◽

1992 ◽

Vol 262 (1) ◽

pp. E1-E5 ◽

Cited By ~ 14

Author(s):

A. G. Baillie ◽

P. J. Garlick

Keyword(s):

Protein Synthesis ◽

Adult Female ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Fiber Type ◽

Female Rats ◽

Adult Rats ◽

Fractional Rate ◽

The Individual

One-year-old adult female rats were fasted for 12 or 36 h followed by a 30-min infusion of insulin. The responses of the fractional rate of protein synthesis (Ks) in the individual muscles (measured in vivo) to fasting were small and mostly nonsignificant. After 12 h of fasting, only the epitrochlearis muscle (ET) showed a significant decrease in Ks, and, even after 36 h of fasting, a significant decrease in Ks was seen in only ET, extensor digitorum longus, and tensor fasciae latae (TFL). After the 36-h fast, infusion of insulin restored the fed Ks in all muscles except TFL. The fiber-type composition of the individual muscles appeared to influence the muscles' responsiveness to the fasting, since the highly glycolytic TFL was the most sensitive (particularly after 36 h of fasting), whereas the highly oxidative adductor longus and soleus muscles were unaffected by either fasting or insulin. In a second experiment, refeeding of fasted adult rats also had little effect on Ks, consistent with the low sensitivity to fasting shown by the first experiment. The parallel results in the two experiments confirmed that the low responsiveness to fasting and insulin infusion in these adult rats was not a result of failure to absorb in “fed” animals or insufficient levels of insulin during insulin infusions. In contrast, a third experiment showed that muscle protein synthesis in the gastrocnemius muscle from young adult (5-mo-old) female rats was significantly reduced after only 12 h of fasting.

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HORMONAL ACTION ON MONOAMINE OXIDASE ACTIVITY IN RATS

Canadian Journal of Biochemistry ◽

10.1139/o67-042 ◽

1967 ◽

Vol 45 (3) ◽

pp. 355-362 ◽

Cited By ~ 30

Author(s):

A. Ho-Van-Hap ◽

L. M. Babineau ◽

L. Berlinguet

Keyword(s):

Monoamine Oxidase ◽

Adult Female ◽

Oxidase Activity ◽

Female Rats ◽

Monoamine Oxidase Activity ◽

Adult Rats ◽

Young Rats ◽

Mao Activity ◽

Hormonal Action

Male young and adult rats were injected with thyroxin, hydrocortisone and puromycin. Monoamine oxidase (MAO) activity was studied in liver, brain, kidney, and heart with L-tryptamine-2-14C as substrate. After thyroxin treatment, heart MAO increased in young animals but decreased in adult animals. Thyroxin decreased liver MAO in adult animals. Brain MAO remained constant in all experiments, whereas kidney MAO showed a slight decrease after thyroxin injection. In young rats, puromycin did not prevent the increase in heart MAO caused by thyroxin injection. Hydrocortisone did not enhance MAO activity in liver, brain and heart. Of all organs studied, only the heart showed a marked increase of MAO with age. In female rats, thyroxin has little effect on brain and liver MAO, whereas it increases MAO activity in the heart of young and adult animals by 67% and 32% respectively. Adult female rats have twice as much heart MAO as males.

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Prenatal exposure to ethanol causes partial diabetes insipidus in adult rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00223.2003 ◽

2004 ◽

Vol 287 (2) ◽

pp. R277-R283 ◽

Cited By ~ 11

Author(s):

Daniel S. Knee ◽

Aileen K. Sato ◽

Catherine F. T. Uyehara ◽

John R. Claybaugh

Keyword(s):

Diabetes Insipidus ◽

Water Intake ◽

Plasma Osmolality ◽

Liquid Diet ◽

Female Rats ◽

Adult Rats ◽

Pregnant Rats ◽

Adult Rat ◽

Mrna Content ◽

The Right

Chronic consumption of ethanol in adult rats and humans leads to reduced AVP-producing neurons, and prenatal ethanol (PE) exposure has been reported to cause changes in the morphology of AVP-producing cells in the suprachiasmatic nucleus of young rats. The present studies further characterize the effects of PE exposure on AVP in the young adult rat, its hypothalamic synthesis, pituitary storage, and osmotically stimulated release. Pregnant rats were fed a liquid diet with 35% of the calories from ethanol or a control liquid diet for days 7–22 of pregnancy. Water consumption and urine excretion rate were measured in the offspring at 60–68 days of age. Subsequently, the offspring were infused with 5% NaCl at 0.05 ml·kg−1·min−1 with plasma samples taken before and at three 40-min intervals during infusion for measurement of AVP and osmolality. Urine output and water intake were ∼20% greater in PE-exposed rats than in rats with no PE exposure, and female rats had a greater water intake than males. The relationship between plasma osmolality and AVP in PE-exposed rats was parallel to, but shifted to the right of, the control rats, indicating an increase in osmotic threshold for AVP release. Pituitary AVP was reduced by 13% and hypothalamic AVP mRNA content was reduced by 35% in PE-exposed rats. Our data suggest that PE exposure can cause a permanent condition of a mild partial central diabetes insipidus.

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Effect of streptozotocin diabetes on polysomal aggregation and protein synthesis rate in the liver of pregnant rats and their offspring

Bioscience Reports ◽

10.1007/bf01200211 ◽

1995 ◽

Vol 15 (1) ◽

pp. 15-20 ◽

Cited By ~ 3

Author(s):

M. E. Martin ◽

A. M. Garcia ◽

L. Blanco ◽

E. Herrera ◽

M. Salinas

Keyword(s):

Protein Synthesis ◽

Streptozotocin Diabetes ◽

Diabetic Rats ◽

Female Rats ◽

Synthesis Rate ◽

Protein Synthesis Rate ◽

Pregnant Rats ◽

Free System ◽

Rna Concentration

To study the effect of diabetes on hepatic protein synthesis and polysomal aggregation in pregnant rats, female rats were treated with streptozotocin prior to conception. Some animals were mated, and studied at day 20 of pregnancy, whereas, others were studied in parallel under non pregnant conditions. The protein synthesis rate measured with an “in vitro” cell-free system was higher in pregnant than in virgin control rats. It decreased with diabetes in both groups, although values remained higher in diabetic pregnant rats than in the virgin animals. The fetuses of diabetic rats had a lower protein synthesis rate than those from controls, although they showed a higher protein synthesis rate than either their respective mothers or virgin rats. Liver RNA concentration was higher in control and diabetic, pregnant rats than in virgin rats, and the effect of diabetes decreasing this parameter was only significant for pregnant rats. Liver RNA concentration in fetuses was lower than in their mothers, and did not differ between control and diabetic animals. The decreased protein synthesis found in diabetic animals was accompanied by disaggregation of heavy polysomes into lighter species, indicating an impairment in peptide-chain initiation.

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