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1.
Article in English | MEDLINE | ID: mdl-30877984

ABSTRACT

Sensitive and accurate measurement of androstane-3ß,17ß-diol and androstane-3α,17ß-diol in the circulation is important for clinical research and accurate clinical diagnosis. This report describes a highly sensitive, specific, precise and reliable assay for the simultaneous accurate measurement of serum androstane-3α,17ß-diol and androstane-3ß,17ß-diol in postmenopausal women. The LLOQ of 1 pg/mL has been achieved with nicotinic acid derivatization, which is superior to picolinic acid by a factor of 5 to 10 in terms of signal to noise ratio. The difference is attributed to the higher acidity of picolinic acid which forms a more stable intermediate, thus decreasing derivatization efficiency. Potential interference from androstane-3α, 17α-diol, androstane-3ß, 17α-diol, and 5-androstenediol has been well separated from the two target diols. The high level of specificity has been determined by well-developed chromatography and ion ratio monitoring. A good linearity in the range of 1 pg/mL to 200 pg/mL (0.03 pg to 6 pg on column) was obtained for both compounds at R > 0.998. The bias and coefficients of variation of all the QC levels are within the range of 10% while the recovery in both charcoal-stripped and unstripped human serum is around 85%. The matrix effect was evaluated and the results well met the acceptance criteria according to the guidelines of bioanalytical method development and validation. Using this newly developed method, the concentrations of both androstane-3α,17ß diol and androstane-3ß,17ß diol were measured in normal postmenopausal serum, where the concentrations range from 2 pg/mL to 32 pg/mL for androstane-3α,17ß diol and from 1 pg/mL to 10 pg/mL for androstane-3ß,17ß diol, respectively.


Subject(s)
Androstanes/blood , Chromatography, Liquid/methods , Postmenopause/metabolism , Tandem Mass Spectrometry/methods , Female , Humans , Limit of Detection , Linear Models , Postmenopause/blood , Reproducibility of Results
2.
Steroids ; 76(12): 1351-7, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21787799

ABSTRACT

BACKGROUND: Epilepsy in women may be associated with reproductive disorders and alterations in serum steroid levels. Some steroids can be induced by epilepsy and/or treatment with antiepileptic drugs; however, there are still limited data available concerning this effect on the levels of other neuroactive steroid metabolites such as 3a-hydroxy-5a/b-reduced androstanes. AIM: To evaluate steroid alterations in women with epilepsy (WWE) on lamotrigine monotherapy. SUBJECTS AND METHODS: Eleven WWE and 11 age-matched healthy women underwent blood sampling in both phases of their menstrual cycles (MCs). The steroid metabolome, which included 30 unconjugated steroids, 17 steroid polar conjugates, gonadotropins, and sex hormone-binding globulin (SHBG), was measured using gas chromatography-mass spectrometry (GC-MS) and radioimmunoassay (RIA). RESULTS: WWE had lower cortisol levels (status p<0.001), but elevated levels of unconjugated 17-hydroxypregnenolone (status p<0.001). Progesterone was higher in the follicular menstrual phase (FP) in WWE than in the controls (status×menstrual phase p<0.05, Bonferroni multiple comparisons p<0.05), whereas 17-hydroxyprogesterone was higher in WWE in both menstrual phases (status p<0.001). The steroid conjugates were mostly elevated in WWE. The levels of 5α/ß-reduced androstanes in WWE that were significantly higher than the controls were etiocholanolone (status p<0.001), 5α-androstane-3α,17ß-diol (status p<0.001), and the 5α/ß-reduced androstane polar conjugates (status p<0.001). CONCLUSIONS: WWE showed a trend toward higher circulating 3α-hydroxy-5α/ß-reduced androstanes, increased activity of 17α-hydroxylase/17,20 lyase in the Δ(5)-steroid metabolic pathway, and increased levels of the steroid polar conjugates.


Subject(s)
17-alpha-Hydroxypregnenolone/blood , Androstanes/blood , Androstanes/metabolism , Anticonvulsants/therapeutic use , Epilepsy/drug therapy , Epilepsy/metabolism , Triazines/therapeutic use , Adult , Androstanols/blood , Anticonvulsants/adverse effects , Female , Humans , Lamotrigine , Metabolome , Steroid 17-alpha-Hydroxylase/blood , Triazines/adverse effects
3.
J Steroid Biochem Mol Biol ; 122(4): 239-52, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20541012

ABSTRACT

Only limited data is available concerning the role of unconjugated Δ(5) C19-steroids and almost no data exists regarding the neuroactive C21 and C19 3α-hydroxy-5α/ß-metabolites in men with epilepsy. To evaluate the alterations in serum neuroactive steroids and related substances in adult men with epilepsy on valproate and carbamazepine monotherapy, we have measured 26 unconjugated steroids, 18 steroid polar conjugates, gonadotropins and sex hormone binding globulin (SHBG) in 6 and 11 patients on valproate and carbamazepine monotherapy, respectively, and in 19 healthy adult men, using the GC-MS and immunoassays. Decreased testosterone, free androgen index, free testosterone, androstenediol, 5α-androstane-3α,17ß-diol (androstanediol), androsterone, epiandrosterone, DHEA, 7ß-hydroxy-DHEA, and DHEAS levels were associated with epilepsy per se. Valproate (VPA) therapy increased 5α-dihydrotestosterone, androsterone, epiandrosterone, DHEA, DHEAS, and 7ß-hydroxy-DHEA levels. Decrease in pregnenolone and 17-hydroxypregnenolone were associated with epilepsy with no effect of antiepileptic drugs (AEDs). Alternatively, the increase in progesterone levels was linked to epilepsy and VPA further increased progesterone levels. Reduced steroid 20α-hydroxy-metabolites and cortisol were connected with epilepsy without an effect of AEDs. Carbamazepine induced only slight decrease in isopregnanolone, 5α,20α-tetrahydroprogesterone, and androstanediol levels.


Subject(s)
Anticonvulsants/therapeutic use , Carbamazepine/therapeutic use , Epilepsy/drug therapy , Steroids/blood , Valproic Acid/therapeutic use , Adult , Androstanes/blood , Gas Chromatography-Mass Spectrometry , Gonadotropins/blood , Humans , Male , Pregnenolone/blood , Sex Hormone-Binding Globulin/metabolism , Steroids/metabolism , Testosterone/analogs & derivatives , Testosterone/blood
4.
BMC Public Health ; 8: 72, 2008 Feb 23.
Article in English | MEDLINE | ID: mdl-18294394

ABSTRACT

BACKGROUND: Studies investigating the association of cadmium and sex steroid hormones in men have been inconsistent, but previous studies were relatively small. METHODS: In a nationally representative sample of 1,262 men participating in the morning examination session of phase I (1998-1991) of the third National Health and Nutrition Examination Survey, creatinine corrected urinary cadmium and serum concentrations of sex steroid hormones were measured following a standardized protocol. RESULTS: After adjustment for age and race-ethnicity, higher cadmium levels were associated with higher levels of total testosterone, total estradiol, sex hormone-binding globulin, estimated free testosterone, and estimated free estradiol (each p-trend < 0.05). After additionally adjusting for smoking status and serum cotinine, none of the hormones maintained an association with urinary cadmium (each p-trend > 0.05). CONCLUSION: Urinary cadmium levels were not associated with sex steroid hormone concentrations in a large nationally representative sample of US men.


Subject(s)
Cadmium/urine , Estradiol/blood , Prostatism/blood , Sex Hormone-Binding Globulin/analysis , Testosterone/blood , Androstanes/blood , Cross-Sectional Studies , Humans , Male , Middle Aged , Smoking/blood , Smoking/urine
5.
Steroids ; 72(11-12): 792-801, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17716701

ABSTRACT

Certain androstane steroids (AS) modulate ionotropic receptors, as do the pregnane steroids. Whereas women produce significant amounts of neuroactive progesterone metabolites, the steroid neuromodulators in men originate mainly from the 3-oxo-4-ene C(19)-steroids, which are converted to their 3alpha- and 3beta-hydroxy-5alpha/5beta-reduced metabolites. The neuromodulating effects of AS prompted us to monitor circulating levels of the steroids to estimate metabolic pathways in the periphery that may influence brain concentrations of AS. Hence, the serum levels of 20 steroids and 16 steroid polar conjugates including 17-oxo- and 17beta-hydroxy-derivatives of 5alpha/beta-androstane-3alpha/beta-hydroxy-androstane steroids were quantified in 15 men (16-62 years of age) using GC-MS. The conjugated AS for the most part reached micromolar concentrations, these being two or three orders of magnitude higher than those of the free steroids. The ratios of conjugates to free steroids were one to two orders of magnitude higher than the values for the corresponding pregnane steroids. This data suggested that conjugation may considerably restrain the transport of free AS from the periphery into the central nervous system.


Subject(s)
Androstanes/blood , Gas Chromatography-Mass Spectrometry/methods , Adolescent , Adult , Androstanes/chemistry , Androstenedione/chemistry , Humans , Male , Middle Aged , Pregnanes/blood , Pressure , Temperature , Testosterone/chemistry , Trimethylsilyl Compounds/analysis
6.
Epilepsia ; 47(11): 1945-8, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17116037

ABSTRACT

PURPOSE: To compare serum levels of neuroactive steroids among men with epilepsy who take various antiepileptic drugs, untreated men with epilepsy and normal controls (NC). METHODS: Subjects were 85 men with localization-related epilepsy [unmedicated >6 months (No Rx)-10, carbamazepine (CBZ)-25, phenytoin (PHT)-25, lamotrigine (LTG)-25] and 25 NC. Sexual function scores (S-Score), hormone levels [dehydroepiandrosterone sulfate (DHEAS), bioactive (BA) testosterone (T), estradiol (BAE), and androstanediol (BAL)] and the ratios of inhibitory to excitatory neuroactive metabolites of T, i.e., BAL/BAE, were compared among groups. RESULTS: S-scores, DHEAS, and bioactive testosterone (BAT) were significantly (p < 0.05) lower and BAL and BAL/BAE were significantly higher among CBZ and PHT groups than among NC and LTG groups. LTG did not differ from NC in any of these measures. BAT correlated significantly with BAL/BAE for PHT (r = 0.44, p = 0.02) and CBZ (r = 0.42, p = 0.03) but not for NC (r = 0.03, p = NS) and LTG (r = 0.06, p = NS) groups. CONCLUSIONS: In comparison to LTG, enzyme inducing AEDs (CBZ, PHT) are associated with a more favorable neuroactive steroid balance (lower DHEAS and higher BAL/BAE) for seizure management, but at the expense of reduced serum bioavailable testosterone levels and sexual function.


Subject(s)
Androgens/blood , Anticonvulsants/pharmacology , Anticonvulsants/therapeutic use , Epilepsies, Partial/blood , Epilepsies, Partial/drug therapy , Steroids/blood , Adolescent , Adult , Androstanes/blood , Biological Availability , Carbamazepine/pharmacology , Carbamazepine/therapeutic use , Dehydroepiandrosterone/blood , Enzyme Induction/drug effects , Estradiol/blood , Humans , Lamotrigine , Male , Middle Aged , Phenytoin/pharmacology , Phenytoin/therapeutic use , Sexual Dysfunctions, Psychological/blood , Sexual Dysfunctions, Psychological/diagnosis , Sexual Dysfunctions, Psychological/psychology , Testosterone/blood , Testosterone/metabolism , Triazines/pharmacology , Triazines/therapeutic use
7.
J Clin Endocrinol Metab ; 90(10): 5647-55, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16030154

ABSTRACT

CONTEXT: Combination of a GnRH antagonist (acyline), types I and II, 5alpha-reductase inhibitor (dutasteride) or levonorgestrel (LNG) with testosterone (T) treatment may augment the suppression of spermatogenesis and intratesticular (iT) steroids. OBJECTIVE: The objective of this study was to assess the effects of combined hormonal contraceptive regimens on germ cell populations and iT steroids. DESIGN, SETTING, AND PARTICIPANTS: Twenty-nine normal health men enrolled in this prospective, randomized, 14-wk study at the University of Washington. INTERVENTION(S): Twenty-two men (n = 5-6/group) received 8 wk of T enanthate (TE; 100 mg, i.m., weekly) combined with 1) 125 microg LNG daily, orally; 2) 125 microg LNG plus 0.5 mg dutasteride daily, orally; 3) 300 microg/kg acyline twice weekly, s.c.; or 4) 125 microg LNG daily, orally, plus 300 microg/kg acyline twice weekly, s.c. Subjects then underwent a vasectomy and testicular biopsy. Control men (n = 7) proceeded directly to surgery. MAIN OUTCOME MEASURE(S): The main outcome measures were germ cells and iT steroids [T, dihydrotestosterone, 3alpha- and beta-androstanediol (Adiol), and estradiol (E2)]. RESULTS: High iT levels of all androgens (6- to 123-fold serum levels) and E2 (407-fold serum levels) were found in control men. iTT (1.9-2.6% control; P < 0.001) and iT3betaAdiol (16-34% control; P < 0.05) levels decreased with all treatments. iT dihydrotestosterone (13-29% control; P < 0.05) and iT3alphaAdiol (44-47% control; P < 0.05) levels decreased with all but the TE plus LNG treatment. iTE2 levels decreased only in the TE plus acyline group (28% control; P = 0.01). Germ cells from type B spermatogonia onward were suppressed, with no differences between groups found. Variable sites of impairment of germ cell progression were evident between men (spermagonial maturation, meiosis 1 entry, and spermiation). Other than a negative correlation between iT3alphaAdiol and haploid germ cell number (P < 0.006), no correlations between germ cell number and gonadotropins, sperm concentration, or iT steroids were found. CONCLUSIONS: A similar high testicular:serum gradient exists for E2 and T in normal men, and 8 wk of gonadotropin suppression markedly reduces iTT, with 5alpha-reduced androgens and E2 levels decreasing to a much lesser degree. The heterogeneity of the germ cell response, regardless of treatment, gonadotropins or iT steroids, points to the individual sensitivity of sites in germ cell development, which is worthy of additional exploration.


Subject(s)
5-alpha Reductase Inhibitors , Enzyme Inhibitors/pharmacology , Gonadotropin-Releasing Hormone/antagonists & inhibitors , Levonorgestrel/pharmacology , Progesterone Congeners/pharmacology , Spermatogenesis/drug effects , Steroids/metabolism , Testis/drug effects , Testis/metabolism , Testosterone/pharmacology , Adult , Androstanes/blood , Azasteroids/pharmacology , Dihydrotestosterone/blood , Dutasteride , Estradiol/blood , Germ Cells/drug effects , Humans , Male , Prospective Studies , Sertoli Cells/drug effects , Testosterone/blood , Vasectomy
8.
Nutr Cancer ; 41(1-2): 41-6, 2001.
Article in English | MEDLINE | ID: mdl-12094627

ABSTRACT

Soy beans contain high levels of the isoflavones genistein and daidzein and their glycosides and have been implicated in the prevention of prostate cancer, possibly via their effects on sex hormone metabolism. The aim of this study was to assess the relation between dietary soy intake and sex hormone levels in a cross-sectional analysis of 696 men with a wide range of soy intakes. Soy milk intake was measured using a validated semiquantitative food frequency questionnaire, and serum hormone concentrations were measured by immunoassay. Multiple regression was used to investigate the association between soy milk intake, an index of isoflavone intake, and hormone levels after adjustment for pertinent confounders. Soy milk intake was not associated with serum concentrations of testosterone, free testosterone, androstanediol glucuronide, sex hormone-binding globulin, or luteinizing hormone. These results suggest that soy milk intake, as a marker of isoflavone intake, is not associated with serum sex hormone concentrations among free-living Western men.


Subject(s)
Beverages , Glycine max , Gonadal Steroid Hormones/blood , Adult , Androstanes/blood , Body Mass Index , Cross-Sectional Studies , Diet, Vegetarian , Exercise , Glucuronides/blood , Humans , Isoflavones/administration & dosage , Luteinizing Hormone/blood , Male , Middle Aged , Regression Analysis , Sex Hormone-Binding Globulin/analysis , Smoking , Surveys and Questionnaires , Testosterone/blood , United Kingdom
9.
Acta bioquím. clín. latinoam ; 31(4): 395-406, dic. 1997. ilus, tab
Article in Spanish | LILACS | ID: lil-217043

ABSTRACT

En la última década se ha implementado una serie de análisis bioquímicos que permiten identificar varios tipos de líquidos quísticos (LQs). En el presente trabajo se confirma la presencia de polipéptidos y esteroides conjugados -como el factor de crecimiento epidérmico (FCE), el sulfato de dehidroepiandrosterona (S-DHEA) y el androstano-3Ó, 17ß-diol glucurónido (3Ó-Adiol G)- a veces en concentraciones muy elevadas con respecto a los niveles encontrados simultáneamente en el plasma circulante. Como contraste, la concentración del cortisol apenas alcanza a un 20 por ciento del normalmente hallado en el plasma. Se demuestra además que la concentración intraquística del 3Ó-Adiol G se correlaciona positiva y significativamente con la del S-DHEA (r = 0,8744, p < 0,0001) y con el FCE (r = 0,8949, p < 0,0001), con amplia variabilidad en los resultados. Se establece también una correlación negativa entre el 3Ó-Adiol G y el cociente Na/K (r = - 0,6592, p = 0,0001). Por último, se determinan los niveles de la gonadotrofina coriónica (hCG), utilizando un sistema automatizado de quimioluminiscencia, demostrándose que esta glicoproteína se encuentra en cantidades determinables (> 1,1 mUI/ml) en el 73,8 por ciento de los LQs analizados. En el 57,4 por ciento los niveles superan a los encontrados normalmente en el plasma que oscilan entre < 1,1 mUl/ml y 5,5 mUl/ml. En un 4,9 por ciento las concentraciones resultan significativamente elevadas, alcanzando hasta las 1.000 mUl/ml. Se demuestra una correlación negativa con alta significación estadística entre los valores normalizados de la hCG con los niveles del S-DHEA, del 3Ó-Adiol G y del FCE y una correlación positiva con el cociente NA/K. Se discute la posibilidad de que el FCE, los esteroides conjugados y la hCG puedan ser sintetizados de novo en el tejido epitelial que recubre las paredes del quiste


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Androstanes/analysis , Androstanols/analysis , Chorionic Gonadotropin , Dehydroepiandrosterone/biosynthesis , Fibrocystic Breast Disease , Epidermal Growth Factor/biosynthesis , Fluids and Secretions/chemistry , Androstanes/blood , Androstanols/blood , Chorionic Gonadotropin/adverse effects , Chorionic Gonadotropin/biosynthesis , Dehydroepiandrosterone/blood , Epidermal Growth Factor/blood , Hydrocortisone/analysis , Hydrocortisone/blood , Biomarkers, Tumor/analysis , Potassium/analysis , Potassium/blood , Sodium/analysis , Sodium/blood
10.
Acta bioquím. clín. latinoam ; 31(4): 395-406, dic. 1997. ilus, tab
Article in Spanish | BINACIS | ID: bin-18113

ABSTRACT

En la última década se ha implementado una serie de análisis bioquímicos que permiten identificar varios tipos de líquidos quísticos (LQs). En el presente trabajo se confirma la presencia de polipéptidos y esteroides conjugados -como el factor de crecimiento epidérmico (FCE), el sulfato de dehidroepiandrosterona (S-DHEA) y el androstano-3O, 17ß-diol glucurónido (3O-Adiol G)- a veces en concentraciones muy elevadas con respecto a los niveles encontrados simultáneamente en el plasma circulante. Como contraste, la concentración del cortisol apenas alcanza a un 20 por ciento del normalmente hallado en el plasma. Se demuestra además que la concentración intraquística del 3O-Adiol G se correlaciona positiva y significativamente con la del S-DHEA (r = 0,8744, p < 0,0001) y con el FCE (r = 0,8949, p < 0,0001), con amplia variabilidad en los resultados. Se establece también una correlación negativa entre el 3O-Adiol G y el cociente Na/K (r = - 0,6592, p = 0,0001). Por último, se determinan los niveles de la gonadotrofina coriónica (hCG), utilizando un sistema automatizado de quimioluminiscencia, demostrándose que esta glicoproteína se encuentra en cantidades determinables (> 1,1 mUI/ml) en el 73,8 por ciento de los LQs analizados. En el 57,4 por ciento los niveles superan a los encontrados normalmente en el plasma que oscilan entre < 1,1 mUl/ml y 5,5 mUl/ml. En un 4,9 por ciento las concentraciones resultan significativamente elevadas, alcanzando hasta las 1.000 mUl/ml. Se demuestra una correlación negativa con alta significación estadística entre los valores normalizados de la hCG con los niveles del S-DHEA, del 3O-Adiol G y del FCE y una correlación positiva con el cociente NA/K. Se discute la posibilidad de que el FCE, los esteroides conjugados y la hCG puedan ser sintetizados de novo en el tejido epitelial que recubre las paredes del quiste (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Epidermal Growth Factor/biosynthesis , Chorionic Gonadotropin/diagnosis , Dehydroepiandrosterone/biosynthesis , Androstanes/analysis , Androstanols/analysis , Fibrocystic Breast Disease/metabolism , Fluids and Secretions/chemistry , Epidermal Growth Factor/blood , Chorionic Gonadotropin/biosynthesis , Chorionic Gonadotropin/adverse effects , Dehydroepiandrosterone/blood , Androstanes/blood , Androstanols/blood , Sodium/analysis , Sodium/blood , Potassium/analysis , Potassium/blood , Hydrocortisone/analysis , Hydrocortisone/blood , Biomarkers, Tumor/analysis
11.
Horm Metab Res ; 28(8): 381-3, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8886824

ABSTRACT

The differential diagnosis between pancreatic cancer and chronic pancreatitis is extremely difficult. Beside CA19-9 level determinations, many tests have been tried with the aim to facilitate this distinction. Serum androgen levels have been used for this purpose. To further explore the value of androgen markers in differentiating pancreatic cancer from chronic pancreatitis we determined the serum levels of androstanediol glucuronide and of androgens in the two groups of patients and compared them with CA19-9 levels. A total of 25 males were entered into the study. Of these, 13 patients had pancreatic cancer and 12 chronic pancreatitis. They were comparable as to their body weight and age. Patients with pancreatic cancer had significantly lower serum testosterone, dihydrotestosterone and androstanediol glucuronide levels, but not testosterone/dihydrotestosterone ratios when compared to patients with chronic pancreatitis. Only androstanediol glucuronide and dihydrotestosterone serum concentrations had such a small overlap between the two groups that could be used for differentiation, their sensitivity and specificity being comparable to those of CA19-9 levels. The present study has shown for the first time that serum androstanediol glucuronide levels in male patients with pancreatic cancer are significantly lower than in those patients with chronic pancreatitis. Furthermore, the sensitivity and specificity of serum andorstanediol glucuronide levels which can be used to differentiate between pancreatic cancer and chronic pancreatitis are comparable to those of CA19-9.


Subject(s)
Androstanes/blood , Glucuronates/blood , Pancreatic Neoplasms/diagnosis , Pancreatitis/diagnosis , Aged , Androgens/blood , CA-19-9 Antigen , Diagnosis, Differential , Dihydrotestosterone/blood , Humans , Male , Middle Aged , Testosterone/blood
12.
Steroids ; 57(2): 76-81, 1992 Feb.
Article in English | MEDLINE | ID: mdl-1621260

ABSTRACT

In humans, the onset of adrenache has been found to occur with the appearance of the zona reticularis, the inner zone of the adrenal cortex. Since an increase in the volume of adrenal cortex during maturation in the guinea pig has been associated with the growth of the zona reticularis, we were interested in investigating the changes in adrenal steroidogenesis during maturation in this species. In addition, the effect of androgens on adrenal steroidogenesis was studied. We demonstrated that between 1 and 10 weeks of age, a period of maximal growth of the adrenals in the guinea pig, there is a decrease in the concentrations of adrenal pregnenolone, cortisol, dehydroepiandrosterone, testosterone, androstenedione, and 11 beta-hydroxyandrostenedione, suggesting lower steroid production by the guinea pig adrenals. In plasma, we observed that the concentration of 11 beta-hydroxyandrostenedione (the sole C19 steroid present after castration) remained unchanged during maturation, while cortisol and corticosterone were lower between 1 and 4 weeks of age. Although castration as well as the administration of the antiandrogen flutamide had no effect on adrenal steroidogenesis, dihydrotestosterone caused an inhibition of cortisol and corticosterone levels in the adrenals while the concentrations of progestins (namely, pregnenolone, 17-hydroxypregnenolone, progesterone, and 17-hydroxyprogesterone) tended to increase in the adrenals, thus suggesting that dihydrotestosterone induces a blockade in the steroidogenic pathway.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Adrenal Cortex/metabolism , Dihydrotestosterone/pharmacology , Steroids/biosynthesis , Zona Reticularis/metabolism , Adrenal Cortex/growth & development , Androstanes/blood , Androstanes/metabolism , Animals , Castration , Flutamide/pharmacology , Guinea Pigs , Male , Pregnenes/blood , Pregnenes/metabolism , Radioimmunoassay , Steroids/blood , Zona Reticularis/growth & development
13.
Bull Cancer ; 78(7): 611-8, 1991.
Article in French | MEDLINE | ID: mdl-1912672

ABSTRACT

We describe the effect of 12 C19-steroids on human breast cancer hormono-dependent cell growth. 5-Androstene-3 beta, 17 beta diol and 5 alpha-androstane-3 beta, 17 beta diol are the most mitogenic Dehydroepiandrosterone, 5 beta-androstane-3 beta, 17 beta diol and the two 5-androstane-3 alpha, 17 beta diol are less mitogenic. 5 alpha-Dihydrotestosterone and testosterone have no effect at physiologic doses, but can modulate MCF-7 growth at pharmacologic concentrations. Androsterone and etiocholanolone have no effect, whereas androstenedione inhibits MCF-7 cell growth.


Subject(s)
Androstanes/pharmacology , Breast Neoplasms/pathology , Neoplasms, Hormone-Dependent/pathology , Tumor Cells, Cultured/drug effects , Androstanes/blood , Breast Neoplasms/blood , Estradiol , Female , Humans , Menopause/blood , Neoplasms, Hormone-Dependent/blood
14.
J Steroid Biochem ; 32(4): 565-72, 1989 Apr.
Article in English | MEDLINE | ID: mdl-2724960

ABSTRACT

In the possum a marked sex difference has been found in the steroids in adrenal venous plasma. Four 5 beta-pregnane and four 5 alpha (beta) androstane derivatives together with ten 4-ene-3-keto steroids were isolated from the adrenal venous plasma of the female and definitively identified by gas chromatography-mass spectrometry. The major reduced steroids were: 5 beta-pregnane-3 alpha,17 alpha-diol-20-one and 5 beta-pregnane-3 alpha,17 alpha,20 alpha-triol, at concentrations of 52 +/- 12 micrograms/100 ml and 44 +/- 8 micrograms/100 ml mean +/- SEM respectively. The concentration of cortisol was 198 +/- 47 micrograms/100 ml. The concentration of the 2 reduced steroids in peripheral plasma were approx. 100 times less. In contrast the adrenal venous plasma of a male contained 14 steroids of which only three, found in trace amounts, were reduced. The results confirm previous in vitro observations that reduced steroids are produced by the adrenocortical special zone, which is only present in the female. The physiological significance of the presence of reduced steroids of adrenocortical origin in the circulation of the female possum is discussed.


Subject(s)
Adrenal Glands/blood supply , Androstanes/blood , Opossums/blood , Pregnanes/blood , Androstanes/isolation & purification , Animals , Chromatography, High Pressure Liquid , Female , Gas Chromatography-Mass Spectrometry , Mass Spectrometry , Pregnanes/isolation & purification , Regional Blood Flow
15.
Horm Behav ; 18(3): 330-45, 1984 Sep.
Article in English | MEDLINE | ID: mdl-6436162

ABSTRACT

In aging quail, an increasing proportion of males show no sexual behavior. A decrease in the mean size of the tests, cloacal gland, and sternotracheal muscles is also observed. In both sexually active and inactive males, plasma testosterone decreases with age but more so in inactive birds. The behavioral and morphological changes observed during aging are correlated with shifts in the intracellular testosterone metabolism resulting in a change in the ratio of active versus inactive metabolites. In the hypothalamus there is a steady decrease with age of 5 beta-reductase activity in all birds and an increase in 5 alpha-reductase activity only in the birds which remain sexually active. In the cloacal gland, the 5 beta-reductase activity markedly increases with age but more so in the birds which become sexually inactive. These data support the notion that the effects of testosterone are controlled by enzymatic shifts which could modulate the sensitivity to the hormone at the cellular level.


Subject(s)
Aging , Brain/enzymology , Sexual Behavior, Animal/physiology , Testosterone/blood , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism , Androstanes/blood , Androstenedione/blood , Animals , Biotransformation , Copulation/physiology , Coturnix , Dihydrotestosterone/blood , Follicle Stimulating Hormone/blood , Hypothalamus, Posterior/enzymology , Luteinizing Hormone/blood , Male , Oxidoreductases/metabolism , Pituitary Gland/enzymology , Preoptic Area/enzymology
16.
Br J Anaesth ; 55 Suppl 1: 31S-34S, 1983.
Article in English | MEDLINE | ID: mdl-6134540

ABSTRACT

The interaction of three new non-depolarizing neuromuscular blocking agents--atracurium, vecuronium and Duador--on human red cell acetylcholinesterase (AChE; EC 3.1.1.7) and human plasma butyrylcholinesterase (BuChE; EC 3.1.1.8) was investigated. The binding of these neuromuscular blockers to human plasma proteins (protein binding) was also studied with a new method not requiring dialysis. For sake of comparison the protein binding and the interaction of tubocurarine and pancuronium with AChE and BuChE were observed also. None of the drugs studied was a substrate of AChE or BuChE. All had a relatively weak inhibitory effect on AChE (I50 greater than 10(-5) mol litre-1 in assay systems containing 5% haemolysed red cells). Of the three new neuromuscular blockers, vecuronium and Duador were relatively potent inhibitors of BuChE (I50 less than 10(-5) mol litre-1 in assay systems containing 5% plasma), but less potent than pancuronium (I50 = 6.1 X 10(-8) mol litre-1). All neuromuscular blocking drugs tested, especially vecuronium and pancuronium, were strongly (77-91%) bound to plasma proteins.


Subject(s)
Cholinesterase Inhibitors , Isoquinolines/blood , Neuromuscular Blocking Agents/blood , Acetylcholinesterase/blood , Androstanes/blood , Androstanes/pharmacology , Atracurium , Blood Proteins/metabolism , Butyrylcholinesterase/blood , Female , Humans , In Vitro Techniques , Isoquinolines/pharmacology , Male , Neuromuscular Blocking Agents/pharmacology , Pancuronium/analogs & derivatives , Pancuronium/blood , Pancuronium/pharmacology , Protein Binding , Vecuronium Bromide
17.
Biomed Mass Spectrom ; 7(7): 284-7, 1980 Jul.
Article in English | MEDLINE | ID: mdl-7448334

ABSTRACT

The steroid fraction of hemofiltrate contains a large number of unknown steroids, which were separated by a combination of different chromatographic procedures and finally characterized by gas chromatography mass spectrometry. Besides different isomeric 3,16,17-trihydroxyandrostanes in a rather polar fraction a 3,16,17-trihydroxy-11-ketoandrostane was detected, obviously the first naturally occurring representative of 3,11,16,17-oxygen-tetrasubstituted androstanes.


Subject(s)
Androstanes/blood , Uremia/blood , Gas Chromatography-Mass Spectrometry/methods , Humans , Renal Dialysis
19.
Urologe A ; 18(6): 311-5, 1979 Nov.
Article in German | MEDLINE | ID: mdl-388799

ABSTRACT

The most reliable laboratory test for prostate cancer remains prostatic phosphatase determination. With the spectrophotometric method, however, falsely negative results are to be expected in 40% of stage D lesions. In only one third of patients with localized disease results are correctly positive. This poor specificity and sensitivity can be improved by radioimmunoassay (RIA). Using this technique the prostatogenic isoenzyme is elevated in 50% of stage A and in 80% of stage B carcinoma, suggesting RIA for screening. Erythrocyte sedimentation rate or serum iron and copper are not necessarily of prognostic value. Phosphatase determination of bone marrow aspirates also requires the RIA method if differentiation of stage C and D is to be expected. Serum hormone assays are not yet introduced into routine staging programs. Serum and urinary markers such as CEA, polyamines of LDH isoenzymes are unspecific and of uncertain value in prostatic carcinoma. Measurement of urinary hydroxyproline seems a reliable method for the search of osseous spread; other bone diseases have to be excluded. In patients with prostate cancer laboratory tests still represent adjunctive measures in connection with the clinical diagnostic armamentarium of urologists.


Subject(s)
Prostatic Neoplasms/diagnosis , Acid Phosphatase/analysis , Alkaline Phosphatase/analysis , Androstanes/blood , Bone Marrow/enzymology , Carcinoembryonic Antigen/analysis , False Negative Reactions , Humans , Hydroxyproline/urine , Isoenzymes/analysis , Isoleucine/urine , Male , Polyamines/urine , Prostatic Neoplasms/enzymology , Radioimmunoassay
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