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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Steroid delta 4-5 alpha- and delta 4-5 beta-reductase activity was determined in 16 human mammary tumors and 8 DMBA-induced rat mammary tumors using a spectrophotometric assay. Steroid delta 4-5 alpha-reductase was present in all tumors investigated while delta 4-5 beta-reductase was detected in only 6 estrogen receptor negative human breast tumors and absent in all estrogen receptor positive human breast tumors as well as in all rat mammary tumors. Further support for the presence of delta 4-5 beta-reductase was established by using a dual-labelling technique consisting of incubating tumor slices with [14C] testosterone and adding [3H] etiocholanolone, [3H] testosterone and [3H]-5 alpha-dihydrotestosterone at the end of the reaction. Following extraction and chromic acid oxidation, 4-androstenedione, 5 beta-androstanedione and 5 alpha-androstanedione were isolated and purified, and the constancy of the 14C/3H ratio was used as proof of 5 alpha-reductase and 5 beta-reductase. These results were shown to be consistent with the data obtained using the spectrophotometric assay.
Steroids 1979 Jan
PMID:Steroid delta 4-5 beta-reductase in human mammary tumors. 10 50

Studies were undertaken to investigate testicular steroidogenesis in the Rhesus monkey Macaca mulatta. Testicular fragments (50 mg) were incubated for 3 hr with pregnenolone-7-3H or with progesterone-7-3H. The major metabolite of pregnenolone was progesterone (70.1%), with a lesser conversion to 17-hydroxyprogesterone (1.6%), androstenedione (3.3%), and testosterone (7.2%). The delta-5 intermediates 17-hydroxypregnenolone (4.6%) and dehydroepiandrosterone (8.6%) were also identified in the pregnenolone incubates. A majority of the progesterone substrate was not metabolized by the testicular fragments (80.1%), while some conversion to 17-hydroxyprogesterone (3.4%), androstenedione (4.8%), and testosterone (11.7%) occurred in the incubates. These results suggest that testicular fragments from the Rhesus monkey may convert pregnenolone to testosterone through both the delta-4 and the delta-5 pathways.
Steroids 1979 Nov
PMID:Testicular steroidogenesis in the rhesus monkey (Macaca mulatta. 11 75

We recently reported that the baboon testis converts pregnenolone to testosterone through the delta-4 pathway. The present studies were to determine the metabolism of intermediates of the delta-4 and delta-5 pathway by the baboon testis. Fragments (50 mg) were incubated for 3 hr with 10 muCi of the following tritium-labelled substrates: pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, or testosterone. Pregnenolone was converted to testosterone primarily through the delta-4 pathway, with accumulation of progesterone, 17-hydroxyprogesterone and 20alpha-dihydroprogesterone as predominant intermediates. Similar results were obtained in progesterone incubations. 17-hydroxyprogesterone was not efficiently metabolized by the fragments, while 17-hydroxypregnenolone and dehydroepiandrosterone were efficiently converted into testosterone and androstenedione. Androstenedione was metabolized primarily to testosterone, while testosterone was not a suitable substrate. Some 5alpha-androstanediol was identified in each incubate. These results suggest that although testosterone is formed from pregnenolone through the delta-4 pathway, the delta-5 intermediates are more suitable substrates for testosterone synthesis in the baboon testis.
Steroids 1978 Sep
PMID:Testicular steroidogenesis in the baboon Papio anubis. 15 89

Epimerization of 4-pregnene-3 beta,20 alpha-diol into 4-pregnene-3 alpha,20 alpha-diol was achieved under the mild condition of an acidic medium at room temperature. This reaction was favorable for synthesis of 4-pregnene-3 alpha,20 alpha-diol in better yield, after chemical reduction of 20 alpha-hydroxy-4-pregnen-3-one with metal hydrides, which resulted in predominant production of 4-pregnene-3 beta,20 alpha-diol. The by-product which was formed more by raising the temperature was identified as 3,5-pregnadien-20 alpha-ol. This method was also applicable for epimerization of other delta 4-3 beta-hydroxysteroids.
Steroids 1979 Apr
PMID:Novel epimerization of steroidal allylic alcohols. 44 33

The ability of granulosa and theca cells of the human ovarian follicle at different stages of development, as well as stromal and luteal tissues from human ovaries to metabolize androstenedione (delta 4) to testosterone (T), dihydrotestosterone (DHT), estrone (E1) and estradiol (E2) with or without exposure to additional amounts of folicle-stimulating hormone was investigated by in vitro experiments. The results show that all the aforementioned ovarian tissues metabolized delta 4 to DHT. Indeed, with the exception of estrogen-secreting granulosa cells from large antral follicle (greater than 10 mm diameter) and possibly also luteal tissue from mid-luteal phase ovaries, the various ovarian tissues preferentially metabolized delta 4 to DHT instead of E (E1 + E2). Although thecal tissue is a major source of delta 4 in human ovaries it is concluded that the granulosa cells do not interact with the theca for the synthesis of E as the follicle enlarges from 1 to 10 mm in diameter. Indeed, excessive thecal delta 4 during this growth phase probably inhibits normal follicular development. However, as the follicle enlarges beyond 10 mm in diameter, and as the granulosa cells begin to preferentially metabolize delta 4 to E, the two cell-types of the follicle may increasingly interact to enhance the follicular output of E.
Steroids 1979 Oct
PMID:Metabolism of androstenedione by human ovarian tissues in vitro with particular reference to reductase and aromatase activity. 51 12

Ten natural progestins were evaluated for their capacity to inhibit the in vitro motility of rat's uterus. Progestins with their ring A reduced in the 5 beta position were significantly more potent than delta 4-3 keto and 5 alpha reduced progestins. These last progestins were ineffective to inhibit uterine motility excepting 3 alpha-hydroxy-5 alpha-pregnan-20-one which was slightly less effective than progesterone. The potency of the progestins to inhibit uterine motility was related to their capacity to induce membrane stabilization. The data indicates that 5 beta, but not 5 alpha reduction of progesterone, may be important for regulating myometrial activity.
Steroids 1979
PMID:In vitro inhibition of rat uterine contractility induced by 5 alpha and 5 beta progestins. 57 42

Some of antihypertensives, opiate antagonist and antifungal agent can interfere with sexual function in both men and women. Drug-related effects on sexual function may be difficult to distinguish from the direct action of gonadal function. Clinically well known those agents to have sexual dysfunction were selected and examined the direct effect on rat's testicular steroidogenesis in vitro. Donryu rats were decapitated at 11 weeks old and isolated testes were decapsulated and preincubated with Krebs-Ringer-phosphate buffer (KRP) added with 1 micrograms/flask of LH for 60 min at 37 degrees C. Then, incubation was made with prazosin (1 micrograms), clonidine (5 micrograms), verapamil (10 micrograms), naloxone (5 micrograms) and ketoconazole (150 micrograms), 37 degrees C for 180 min in fresh KRP-buffer, respectively. Steroids were analysed with RIA, and microfluorometry after purification with quantitative thin layer chromatography. Prazosin had a tendency to produce dihydrotestosterone (DHT) indicating a facilitation of 5 alpha-reductase, and clonidine showed a significant production of estradiol (E2) with a slight production of DHT indicating a significant facilitation of aromatase. Verapamil had a action to produce significantly E2 with a slight production of DHT, and naloxone showed a significant production of both DHT and E2. Thus, these two agents showed facilitation of both 5 alpha-reductase and aromatase. Ketoconazole had a significant production of both delta 4-androstenedione (delta 4-A) and E2 while it had a significant inhibition of DHT-production, thus this had a significant production of both aromatase and C17,20-lyase while had a significant inhibitory action of 5 alpha-reductase. These findings indicates that comparatively large doses of central-nervous system depressants are one of the factors that interfere with sexual function, but it is not necessary to have direct action to testicular function, however present study revealed that some of them can cause gonadal damage and consequently progressive loss of libido.
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PMID:Disturbance or relatively important actions of antihypertensives, antifungal agent and opiate antagonist to the testicular steroidogenesis in rat. 150 73

The metabolism of cortisol by human liver homogenates has been studied. Cortisol delta 4-reductase and dihydrocortisol-3-oxidoreductase activities were distributed in all subcellular fractions. The products of the soluble enzymes were identified. Cortisol and 5 beta-dihydrocortisol were reduced to 3 alpha,5 beta-tetrahydrocortisol, and 5 alpha-dihydrocortisol was reduced to 3 alpha,5 alpha-tetrahydrocortisol. The soluble enzymes showed a wide range of substrate specificity. The 21 substituted cortisol derivatives were not metabolized. The apparent Km values of cortisol delta 4-5 beta-reductase and dihydrocortisol-3 alpha-oxidoreductase for their substrates (cortisol, 5 alpha-dihydrocortisol, and 5 beta-dihydrocortisol) all ranged from 18 to 27 microM. Dexamethasone inhibited the reduction of all of these substrates and the inhibition was abolished by 21 substitution of the dexamethasone. Testosterone was a competitive inhibitor of the reduction of cortisol, 5 alpha-dihydrocortisol, and 5 beta-dihydrocortisol with a Ki ranging from 11 to 32 microM. NADPH was the preferred cofactor for the cortisol delta 4-5 beta-reductase and dihydrocortisol-3 alpha-oxidoreductase. No end product inhibition was observed.
Steroids 1990 Nov
PMID:Human hepatic cortisol reductase activities: enzymatic properties and substrate specificities of cytosolic cortisol delta 4-5 beta-reductase and dihydrocortisol-3 alpha-oxidoreductase(s). 207 15

Effective concentrations50 of androgens, i.e. testosterone, androsterone, androstanediol, 5 beta-dihydrotestosterone and progestins: progesterone, pregnanolone, pregnanedione, epipregnanolone, allopregnanolone and allopregnanedione were assayed on the tonic contractions of the isolated rat myometrium induced by calcium in high-potassium calcium-free depolarizant solutions. Steroids showed their relaxant effect by fadding the sustained contraction induced by calcium in a depolarized state. Also, the addition of the calcium ionophores A-23187 and X-537A reversed the steroid relaxant effect by increasing sharply the tonic contraction. The possibility of steroid-induced relaxation through release of noradrenaline or histamine was discarded by blocking their specific receptors. From the results it is concluded that delta-4 and 5-reduced androgens and progestins produce relaxation by a myogenic mechanism acting on the smooth muscle cell, most likely by directly blocking the calcium channels they causing modulation of: the contraction-relaxation cycle.
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PMID:Non-genomic mechanism of action of delta-4 and 5-reduced androgens and progestins on the contractility of the isolated rat myometrium. 217 88

Ingestion of licorice or treatment with chemical derivatives of glycyrrhetinic acid (GA), an active principle of licorice, can cause hypertension, sodium retention, and hypokalemia. Although GA has been shown to inhibit 11 beta-hydroxysteroid dehydrogenase, it may not be the only hepatic enzyme affected by this licorice derivative. Therefore, we studied the effects of GA on other major hepatic steroid-metabolizing enzymes from adrenalectomized male rats using aldosterone as the substrate; namely, delta 4-5 alpha- and delta 4-5 beta-reductases and 3 alpha- and 3 beta-hydroxysteroid dehydrogenases (3 alpha- and 3 beta-HSD). From these in vitro studies, we demonstrated that GA does not affect either microsomal 5 alpha-reductase or cytosolic 3 alpha-HSD activity. However, GA is a potent inhibitor of cytosolic 5 beta-reductase; the K(is) and K(ii) were calculated from enzyme kinetic analysis to be 6.79 and 5.41 microM, respectively, using the Cleland equation, indicating that GA is a noncompetitive inhibitor of aldosterone. In addition, GA specifically inhibited microsomal 3 beta-HSD enzyme activity by what appears to be a competitive inhibition mechanism, causing a build-up of the intermediate, 5 alpha-dihydroaldosterone (DHAldo). Thus, this study has indicated that GA has a profound effect on hepatic ring A-reduction of aldosterone. Inhibition of 5 beta-reductase and 3 beta-HSD results in decreased synthesis of both 3 alpha, 5 beta-tetrahydroaldosterone (THAldo) and 3 beta, 5 alpha-THAldo and, hence, accumulation of aldosterone and 5 alpha-DHAldo, both potent mineralocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS)
Steroids 1990 Feb
PMID:The effects of the licorice derivative, glycyrrhetinic acid, on hepatic 3 alpha- and 3 beta-hydroxysteroid dehydrogenases and 5 alpha- and 5 beta-reductase pathways of metabolism of aldosterone in male rats. 232 27


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