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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone is a target organ of androgens. The mechanism by which these steroids exert their action within bone cells is still poorly understood. The metabolism of androstenedione, the major circulating androgen in women, was, therefore, assessed in osteoblast-like bone cells cultured from bone of 16 postmenopausal women (mean age, 69 yr; range, 56-80) and 3 elderly men (mean age, 71 yr; range, 69-73) undergoing total hip replacement. Each cell strain was incubated under standardized conditions with varying concentrations of [1,2,6,7-3H]androstenedione (0.05-5 microM). In every instance 5 alpha-reduced metabolites and 17 beta-hydroxysteroids were formed. There was no correlation between the volumetric density of the resected bone and androstenedione metabolism of the corresponding cultured bone cell strains. The apparent Km for the 5 alpha-reductase activity (sum of androstanedione and dihydrotestosterone) of all 19 cell strains was 0.7 +/- 0.1 microM (mean +/- SEM), and the apparent Km for 17 beta-hydroxysteroid dehydrogenase (sum of testosterone and dihydrotestosterone) was 2.3 +/- 0.8 microM (mean +/- SEM), values similar to those reported for other androgen target organs. Our results demonstrate that human osteoblast-like cells have the capacity to transform androstenedione into the more potent biological androgens testosterone and dihydrotestosterone. Since the Km values of both 5 alpha-reductase and 17 beta-hydroxysteroid dehydrogenase exceed the serum androstenedione concentration, the formation of testosterone and dihydrotestosterone appears to be mainly a function of substrate availability.
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PMID:Androstenedione metabolism in cultured human osteoblast-like cells. 161 95

Androgen metabolism was investigated in normal human apocrine glands and in those isolated from age-matched patients with hidradenitis suppurativa. Axillary glands were isolated by shearing and androgen interconverting enzyme activities were measured in cell-free homogenates by incubation with [3H] dehydroepiandrosterone, [3H] androstenedione and [3H] testosterone. The activities (pmol/mg protein/min: mean + SEM) of 3 beta-hydroxysteroid dehydrogenase delta 4-5-isomerase (10.0 +/- 1.2 vs. 5.3 +/- 0.5: n = 5) and 17 beta-hydroxysteroid dehydrogenase (58.1 +/- 4.5 vs. 35.7 +/- 5.2: n = 5) were significantly lower (P less than 0.005) in hidradenitis suppurativa, whereas 5 alpha-reductase activity (12.5 +/- 2.3 vs. 12.5 +/- 2.0: n = 5) was similar. This report suggests that hidradenitis suppurativa cannot be attributed to exaggerated activities of end-organ androgen interconverting enzymes.
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PMID:Androgen metabolism by isolated human axillary apocrine glands in hidradenitis suppurativa. 195 17

In order to delineate differences in the mechanism of androgen action in epithelium (E) and stroma (S) of the human prostate, we studied the 17 beta-hydroxysteroid dehydrogenase (17 beta-HSDH) in these tissues of benign prostatic hyperplasia (BPH). Tissue was obtained by suprapubic prostatectomy. E and S were separated; samples were homogenized in buffer and incubated with [3H] steroids (4-androstenedione (Ae), estrone (E1), or dehydroepiandrosterone (DHEA] and NADH (4.2 mmol/l) as cosubstrate for 60 min at 37 degrees C. Separation and quantification of the metabolites were performed by TLC and LSC, respectively. The main results were: (1) Following incubation with DHEA and E1, only the metabolites 5-androstene-3 beta,17 beta-diol and estradiol, respectively, were found. Following incubation with Ae, testosterone, 5 alpha-dihydrotestosterone and 5 alpha-androstane-3 alpha-(beta),17 beta-diol were detected as metabolites (the sum of these metabolites were used for calculations). (2) The Michaelis constants were identical in E and S (mean +/- SEM (n), mumol/l, Ae 6.92 +/- 1.01, E1 7.84 +/- 0.69, DHEA 3.73 +/- 0.38). (3) The maximum velocity rate for the three substrates in E was 5-10-fold that in S (P at least less than 0.01), the value in the whole tissue homogenate (WT) being intermediate (pmol/mg protein h), for Ae: E 383 +/- 56, S 40 +/- 3, WT 75 +/- 13; for E1: E 362 +/- 71, S 33 +/- 4, WT 63 +/- 8; for DHEA: E 132 +/- 21, S 26 +/- 4, WT 36 +/- 4. On the basis of these results the role of 17 beta-HSDH in forming active androgens and estrogens from less potent precursors is discussed in the stromal and epithelial compartment of the human prostate.
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PMID:17 beta-Hydroxysteroid dehydrogenase in the human prostate: properties and distribution between epithelium and stroma in benign hyperplastic tissue. 244 Nov 44

In an attempt to determine whether the chronic administration of GnRH agonist (GnRH-A) has a direct inhibitory effect on testicular steroidogenesis in the human, the testes of four men with disseminated prostatic cancer who were treated with GnRH-A daily for at least 1 yr were assayed for intratesticular pregnenolone (5-pregnen-3 beta-ol-20-one), progesterone, dehydroepiandrosterone, 17 alpha-hydroxypregnenolone (5-pregnen-3 beta 17 alpha-diol-20-one), 17 alpha-hydroxyprogesterone, androstenedione, and testosterone (T). In addition, testicular 17 alpha-hydroxylase, 17,20-desmolase, and 17 beta-hydroxysteroid dehydrogenase enzyme activities of the delta 4 pathway were measured. These intratesticular steroids and enzyme activities from four GnRH-A-treated patients were compared to those in five men (controls) who were orchiectomized as the primary treatment for their disseminated prostatic cancer and in three other men who were treated for 3-12 months with GnRH-A daily but received, in addition to the daily GnRH-A, 1000 IUhCG, im, every other day for 3 days immediately before their salvage orchiectomy, which was performed when their disease progressed. In the control group, the delta 5-steroids, particularly dehydroepiandrosterone and pregnenolone, represented the majority of the intratesticular steroids. Compared to control values, all intratesticular steroids except delta 4-P (for which there was no difference) were significantly lowered by treatment with GnRH-A. Intratesticular T was reduced by 98% from 328 +/- 139 (+/- SEM) ng/g testis in the control group to 8 +/- 3 in the GnRH-A-treated group (P less than 0.01). The additional treatment with hCG for 3 days in the GnRH-A-treated group reversed the inhibition of all steroids to either control or above control levels, with intratesticular T rising to 1144 +/- 273 ng/g testis. A similar trend was found for all three enzymatic activities, i.e., GnRH-A alone inhibited each of the enzymatic activities, whereas the addition of hCG reversed this inhibition by GnRH-A. These data indicate that the chronic administration of GnRH-A to elderly men results in inhibition in both the delta 4 and delta 5 pathways, with a subsequent decrease in the intratesticular T concentration. The ability of exogenous hCG to reverse both the reduction in delta 4 and delta 5 intratesticular steroid content and the intratesticular enzyme activities induced by GnRH-A treatment supports the concept that GnRH-A does not have a direct inhibitory effect on testicular T biosynthesis.
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PMID:Lack of a direct effect of gonadotropin hormone-releasing hormone agonist on human testicular steroidogenesis. 302 29

Ketoconazole, an orally-active, broad spectrum mycotic agent, was shown to inhibit in vitro human placental microsomal aromatase but was without effect on 3 beta-hydroxysteroid dehydrogenase-isomerase (3 beta-HSD-I) and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activities. The Km of placental aromatase for testosterone was 30 +/- 1.1 nmol/l (mean +/- SEM, n = 6). Inhibition (determined by Lineweaver-Burk plot) was non-competitive with respect to substrate with a Ki value of 3.0 +/- 1.4 mumol/l (mean +/- SEM, n = 6). Ketoconazole was without effect on the 3 beta-HSD-I and 17 beta-HSD activities when using [3H] pregnenolone and [3H] oestradiol, respectively, as substrates. Since ketoconazole is known to inhibit cytochrome P-450-dependent enzyme reactions, the results of the present study support the contention that cytochrome P-450 is involved in the aromatisation process.
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PMID:Effect of ketoconazole on placental aromatase, 3 beta-hydroxysteroid dehydrogenase-isomerase and 17 beta-hydroxysteroid dehydrogenase. 302 21

One-third of the cases of breast cancer in postmenopausal women are hormone-dependent and the lesions regress upon treatment with antiestrogens or inhibition of estrogen biosynthesis. In these patients, estrogens are synthesized in extraglandular tissues from adrenal precursors and re-enter plasma to produce estrone levels of 52 +/- 6.5 pg/ml (mean +/- SEM) and estradiol concentrations of 13.1 +/- 0.7 pg/ml. However, the fact that the levels of estrogen in breast tumor tissue are an order of magnitude higher than plasma levels suggested the possibility of in situ estrogen production. To address this possibility, we measured several enzymes involved in estradiol biosynthesis in human tumors. Forty-eight of 61 tumors contained aromatase (estrogen synthetase) activity ranging from 5-80 pg/gm protein per hour. By comparison, the levels of estrone sulfatase were 10(6) higher, ranging from 0.8-125 micrograms/gm protein per hour. Because the sulfatase enzyme was of lower affinity (i.e., Km = 27 microM) than that of aromatase (i.e., 0.027 microM), the amount of estrogen formed under conditions of similar substrate concentrations was compared and found to be 10-fold higher via the sulfatase enzyme. In 41 additional tumors, the 17 beta-hydroxysteroid dehydrogenase enzyme, catalyzing the conversion of estrone to estradiol, was uniformly present. To test the biologic relevance of the estrone sulfate to estrone to estradiol pathway, estrogen-dependent nitrosomethylurea rat mammary tumors were grown in soft agar in the presence of estrone sulfate. Concentrations of estrone sulfate of 10(-6) microM significantly (p less than 0.01) stimulated colony formation in this system in which 75.5-98.6% of estrone sulfate was converted to estrone and 0.2 to 6% to estradiol. These data support the hypothesis that mammary carcinomas can synthesize estradiol in situ from circulating estrogen precursor and that local conversion is biologically important. On the basis of comparative data, the estrone sulfate to estrone to estradiol pathway is quantitatively more important than that involving androstenedione to estrone to estradiol.
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PMID:Enzymatic control of estrogen production in human breast cancer: relative significance of aromatase versus sulfatase pathways. 352 46

In an attempt to determine whether defective testicular testosterone (T) biosynthesis may be associated with a varicocele, an experimental study was performed in adult rats whereby a unilateral left varicocele was surgically created. At 2, 4, 8, and 12 wk following the creation of the varicocele, intratesticular T as well as the activities of three (17 alpha-hydroxylase, 17,20-desmolase, and 17 beta-hydroxysteroid dehydrogenase) of the five enzymes in the delta 4 pathway of testicular T biosynthesis were measured. Intratesticular T (ng/g testis +/- SEM) in the left testis decreased significantly from 121 +/- 21 in the control group to 59 +/- 8 in the two-wk varicocele group (p less than 0.01), and remained significantly suppressed throughout the experimental period. The T concentrations in the right testis paralleled those in the left in both the control and varicocele animals. At 2 wk following the creation of the varicocele, the activity (nmol/min/testis +/- SEM) of the 17,20-desmolase enzyme decreased significantly, from 115 +/- 8 in the left testis of control rats to 87 +/- 6 in the left testis of the varicocele animals (p less than 0.025), and remained low throughout the 12 weeks of the study. The activity of the 17 alpha-hydroxylase enzyme was significantly decreased at the 8th and 12th weeks of the study, while the 17 beta-hydroxysteroid dehydrogenase activity did not show any significant change during the study period. The enzyme activities in the right testis paralleled those in the left testis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of testicular testosterone biosynthesis following experimental varicocele in rats. 359 58

A direct method for determination of delta 5 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity was employed in isolated Leydig cells (LC) derived from rats on fetal day 19 (Fig) and postnatal (N) days 1, 12, 24, 34 and 45 and adults. The activity of 3 beta-HSD in the adult LC was 1.15 +/- 0.02 (mumole/microgram DNA/hr, mean +/- SEM, n = 73). Activities in the other groups, expressed as a percentage of the respective adult control, were: Fig-38%; N1-39%; N12-8%; N24-89%; N34-166%; and N45-118%. A good correlation was found between histochemical staining for 3 beta-HSD and the quantitive method employed. Using (3H)-DHA as a substrate, LC isolated from F19, N1 and N12 produced testosterone in appreciable amounts (41%, 55% and 20% of the total products respectively) whereas at advanced stages of development (N24 to adulthood) the major product was androstenedione (93 +/- 1%). These findings may be explained by the observed decrease in 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity, due to an insufficient supply of NADPH, in the older vs. earlier stages of development. This study indicates the presence of steroidogenic enzymatic activity in LC throughout development in the rat. It also provides a relatively simple in vitro model for studies of testicular regulation during development.
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PMID:Developmental pattern of delta 5 3 beta-hydroxysteroid dehydrogenase activity in isolated rat Leydig cells. 693 86