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At least 19 recordsLinked to original sources
PubMed1976

Distinct testicular 17-ketosteroid reductases, one in interstitial tissue and one in seminiferous tubules. Differential modulation by testosterone and metabolites of testosterone.

The final step in the biosynthesis of testosterone is the reduction of androstenedione, which is catalyzed by the microsomal enzyme 17-ketosteroid reductase. Evidence is presented which suggests that there are two distinct 17-ketosteroid reductases in rat testes, one in interstitial tissue and one in seminiferous tubules. The two enzymes have different pH optima, 5.6 for the one from interstitial tissue and 6.5 for the one from seminiferous tubules. At the optimum pH, a 70-fold difference in Km values was observed, 17 muM for the interstitial tissue enzyme and 0.25 muM for the enzyme from seminiferous tubules. Testosterone and metabolites of testosterone have very different effects of each of these enzyme activities. The interstitial tissue enzyme activity is inhibited by testosterone and several 5alpha-reduced metabolites of testosterone and by estrogens. The most potent inhibitor of the steroids investigated was 5alpha-androstane-3alpha, 17beta-diol, followed by 17beta-estradiol approximately equal to dihydrotestosterone greater than testosterone greater than estrone greater than estriol. 5alpha-Androstane-3alpha, 17beta-diol and 17beta-estradiol were shown to act by competitive inhibition with apparent Ki values of 2.2 and 3.7 muM, respectively. In contrast, it was demonstrated that among the above steroids, only dihydrotestosterone inhibits the 17-ketosteroid reductase activity of seminiferous tubules and this inhibition was only observed at very high concentrations of inhibitor. Testosterone stimulated the 17-ketosteroid reductase activity of seminiferous tubules. 5alpha-Androstane-3alpha, 17beta-diol at low concentrations stimulated the enzyme activity from seminiferous tubules, while it had no effect at high concentrations. The remainder of the steroids tested had no effect on the 17-ketosteroid reductase activity of seminiferous tubules. The difference in response of the two enzyme activities suggests a mechanism for local regulation of testosterone synthesis in each testicular compartment that does not involve directly pituitary gonadotropins.

17-Ketosteroids↗
PubMed1979

Guinea pig liver aromatic aldehyde-ketone reductases identical with 17 beta-hydroxysteroid dehydrogenase isozymes.

Two NADPH-dependent aromatic aldehyde-ketone reductases purified from guinea pig liver catalyzed oxidoreduction of 17 beta-hydroxysteroids and 17-ketosteroids. One enzyme efficiently oxidized 5 beta-androstanes and reduced 17-ketosteroids of A/B cis configuration, whereas the other enzyme efficiently oxidized 5 alpha-androstanes and equally reduced both 5 alpha-and 5 beta-androstanes of 17-ketosteroids. However, aromatic aldehydes and ketones, and 3-ketosteroids were irreversibly reduced by the two enzymes. The two enzymes utilized NADP+ or NADPH as cofactor, but little activity with NAD+ or NADH was found. Phosphate ions enhanced the NAD+-dependent dehydrogenase activity and NADH-dependent reductase activity of the two enzymes, whereas the activities with NADP+ and NADPH were not affected. The ratios of the two activities of ketone reduction and 17 beta-hydroxysteroid oxidation of the two enzymes were almost constant during the purification steps after the two enzymes had been separated by DEAE-cellulose chromatography. By kinetic studies and electrophoresis and isoelectric focusing experiments it was confirmed that both of the two enzymes were responsile for the reduction aldehydes, ketones, and ketosteroids and for the oxidation of 17 beta-hydroxysteroids. These results indicate that 17 beta-hydroxysteroid dehydrogenases may play important roles in the metabolism of exogeneous aldehydes and ketones as well as steroids.

17-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Clinical assessment of cryptorchid boys by determination of urinary testosterone glucuronide following large doses of human chorionic gonadotropin (hCG).

Urinary TG and fractionated 17-ketosteroid (Drosdowsky) determinations were performed before and after the intramuscular administration of 15,000 IU of human chorionic gonadotropin (hCG) in 10 sexually immature healthy boys and in 12 bilaterally cryptorchid boys. The same basal determinations were made in 11 gonadless girls. Basal serum FSH and LH were determined (by radioimmunoassay) in controls and also in cryptorchid boys. If 15mug/24 h (three SD's of basal excretion in controls) is considered the smallest adequate response, the TG but not the fractionated 17-KS determination assessed fairly well either the presence or the functional capacity of the Leydig cell-containing tissue. Agonadic girls had significantly higher basal excretion of steroids and this is presumably due to their greater absolute body size and to their more advanced bone age.

17-Ketosteroids↗
PubMed1978

The effect of ovarian wedge resection and incision on circulating gonadotropin in patients with polycystic ovarian disease.

Wedge resection (WR) was performed in 12 women with polycystic ovarian disease (PCOD), and Incision was done in 4 PCOD patients without any resection of ovarian tissue. Serum LH, FSH, estradiol-17beta (E2), progesterone, and urinary 17 ketosteroid (17KS) were measured serially before and after surgery. Neither WR nor Incision had any effect on FSH levels. Serum LH levels which had been hypergonadotropic preoperatively, became markedly lower 7--14 days after surgery in 12 wedge-resected and 2 incised patients. Within 7 days after WR there was a significant fall of E2 and a decrease of 17KS. In addition to those hormonal changes observed after WR, BBT charts turned out to be diphasic after the oral administration of dydrogesterone (Duphaston) in 12 out of 17 PCOD patients. The present data suggest that the reduction of the serum LH, induced by an interaction between the ovarian steroidogenesis and the suprapituitary mechanisms, might be involved in the occurrence of ovulation after WR in PCOD patients.

17-Ketosteroids↗
PubMed1978

[Absence of the inhibitor factor of the Mullerian structures. Report of a case].

A 30 year old patient with normal masculine phenotype, karyotype 46 XY with a congenital left inguinal hernia, was studied. This hernia contained (at surgery): uterus, tubes and a hypoplasic vagina, as well as testis. The Müllerian structures and the right testicle, were resected, and left orchidopexy was performed. FSH, LH, testosterone, prolactine, B-HCG in blood by radioimmunoanalysis, total estrogens, 17-ketosteroids and 17-hydroxicorticosteroids in urine, were all normal. Roentgenologic and endoscopic urologic studies were normal. A post-operative study of semen showed moderate oligospermia. The factors involved in masculine sexual differentiation, were reviewed, specially the inhibitory factor of Müllerian structures.

Adult↗
PubMed1975

Antiarrhythmic, haemodynamic and metabolic effects of 3alpha-amino-5alpha-androstan-2beta-ol-17-one hydrochloride in greyhounds following acute coronary artery ligation.

1 The antiarrhythmic, haemodynamic and metabolic effects of a new amino steroid, ORG6001, have been investigated in experimental acute myocardial infarction in anaesthetized greyhounds. 2 ORG6001 administered either intravenously (2-10 mg/kg) or orally (50 mg/kg) significantly reduced the incidence of ventricular ectopic beats in the first 30 min after ligation of the left anterior descending coronary artery. 3 In dogs pretreated with ORG6001, metabolic changes indicative of myocardial ischaemia (lactate production and potassium efflux) were less marked than those occurring in control animals. 4 Antiarrhythmic doses of ORG6001 caused only minimal transient haemodynamic effects. 5 These results suggest that ORG6001 may possess distinct advantages over presently-used antiarrhythmic drugs in the prevention and treatment of the early arrhythmias which occur after myocardial infarction.

17-Ketosteroids↗
PubMed1976

Investigations to characterize a new anti-arrhythmic drug, ORG 6001 including a simple test for calcium antagonism.

1 The compound Org 6001 (3alpha-amino-2beta-hydroxy-5alpha-androstan-17-one hydrochloride) was found in recent experiments to exhibit anti-arrhythmic activity. Evidence is presented in this paper concerning its mode of action. 2 Org 6001 was 1.8 times more potent than procaine as a local anaesthetic on desheathed frog nerve. 3 Org 6001 had no effect on the resting potential of isolated cardiac muscle of rabbit, but greatly reduced the maximum rate of depolarization tion (MRD). The action potential duration TAPD) WAS MARGINALLY PROLONGED IN ATRIAL AND VENTRICULAR MUSCLE. 4 Org 6001 preferentially shortened APD in that part of the Purkinje system in which APD is normally longer than elsewhere, so that APD

17-Ketosteroids↗
PubMed1976

Reduction of 3-oxosteroids in human liver microsomes.

The 3alpha- and 3beta-reduction of the following steroids was studied in human liver microsomes: 5alpha-androstane-3,17-dione, 17beta-hydroxy-5alpha-androstan-3-one, 5alpha-pregnane-3,20-dione, 5beta-pregnane-3,20-dione, 3-oxo-5beta-cholanoic acid and 7alpha-hydroxy-5alpha-cholestan-3-one. With NADH as cofactor there was a preferential 3alpha-reduction of the C19- and C21-3-oxo-steroids and a preferential 3beta-reduction of the C24- and C27-3-oxo-steroids. Substitution of NADH with NADPH influenced reduction of the substrates in different ways, indicating the presence of several 3alpha- and 3beta-hydroxysteroid dehydrogenases with different substrate specificity and specificity towards NADH and NADPH. Only small or insignificant sex differences could be observed in the reductions studied.

17-Ketosteroids↗
PubMed1976

[Sexual hormones in ageing males (author's transl)].

Alterations of sexual hormones in plasma of ageing males occur between the 50th and 60th year of life with individual variations: 1. Decreased values of testosterone in plasma and a poor response to gonadotrophins demonstrate a diminished synthesizing capacity of the testes in old men. 2. The decreased testosterone plasma values are followed by an increase in LH. The response of the anterior pituitary gland to LH-RH stimulation in old men is normal. 3. Under basal conditions estrone as well as estradiol plasma concentrations increase significantly with age because of increased conversion from androgens. 4. Parallel to estrogen plasma values an increased concentration of the sexual hormone binding globulin (SHBG) is found, resulting in a steep decrease of the free (= active) testosterone fraction. 5. Decreased testosterone, which is more strongly bound to SHBG and increased estrone and estradiol plasma values result in an androgen/estrogen imbalance in old men.

17-Ketosteroids↗
PubMed1976

[Gonadotropin induced steriodogenesis in prepubertal boys (author's transl)].

We examined the capacity of reaction in the endocrine tissue of testes in prepubertal boys. 18 boys were endocrinologically healthy, six suffered from cryptorchidism on one or both sides. After a single dose of HCG (5000 IU/m) we found an increase of pregnantriol excretion in the 24 h urine in all subjects studied except in the case of surgically proved anorchia. In all except one boy we found a sharp increase in testosterone after HCG administration.

17-Ketosteroids↗
PubMed1979

Effects of altitude and two decongestant-antihistamine preparations on physiological functions and performance.

Fourteen men were studied to determine the combined effects of two altitudes--388 and 3,810 m or 1,274 and 12,500 ft--and three preparations--lactose placebo, Compound A (Actified, and Compound B (Dristan). Subjects reported least attentiveness with A and greatest with placebo. Fatigue increased significantly with time while energy, interest, and attentiveness decreased. The Multiple Task Performance Battery (MTPB) showed no effects of altitude, drugs, or time on overall performance; however, performance declined with time in several tasks, while problem solving improved. Subjects enjoyed the problem-solving tasks and may have given them preference as levels of interest declined. Though the MTPB overall composite scores did not change significantly, physiological parameters and subjective evaluations indicate that type of compound and time after ingestion are important. Declines in energy and attentiveness 2.5 h after ingestion could result in neglect of important--although routine--tasks. Hypoxia might enhance this effect and consequences might be worse in subjects whose medical conditions require these drugs.

17-Ketosteroids↗