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PubMed2001

Consequence of boar edible tissue consumption on urinary profiles of nandrolone metabolites. II. Identification and quantification of 19-norsteroids responsible for 19-norandrosterone and 19-noretiocholanolone excretion in human urine.

In previous work (Le Bizec et al., Rapid Commun. Mass Spectrom. 2000; 14: 1058), it was demonstrated that a boar meal intake could lead to possible false accusations of abuse of 17beta-nortestosterone in antidoping control. The aim of the present study was to identify and quantify endogenous 19-norsteroids in boar edible tissue at concentrations that can alter the steroid urinary profile in humans, and lead to excretion of 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE). The samples were analysed in two laboratories. The methodologies used for extraction and detection (GC/MS(EI) and LC/MS/MS(APCI+)) are compared and discussed. 19-Norandrostenedione (NAED), 17beta- and 17alpha-nortestosterone (bNT, aNT), and 17beta- and 17alpha-testosterone (bT, aT) were quantified. The largest concentrations of NAED and bNT were observed in testicles (83 and 172 microg/kg), liver (17 and 63 microg/kg) and kidney (45 and 38 microg/kg). A correlation between the bNT and NAED content of a typical meal prepared with boar parts and the excreted concentrations of 19-NA and 19-NE in human urine was demonstrated.

Animals↗

PubMedDate not supplied

Androblastoma: pre-, per- and post-operative steroid hormone and binding protein concentrations in peripheral plasma, cyst fluid and tumor vein.

A case-report of arrhenoblastoma is presented where the endocrine profile has been determined before, during and after removal of the tumor. Sex steroids, cortisol, corticosteroid binding globulin (CBG) and sex steroid binding protein (SBP) were measured in fluid from 2 cysts, tumor vein and peripheral plasma. Hormones were measures by specific RIAs after stepwise chromatography on celite support according to a new elution pattern allowing the resolution of 8 sex steroid in a single chromatographic system. Excessive amounts of androgen, the most prominent being testosterone, and 17-OH-progesterone, but low levels of estrogens and progesterone were found in preoperative plasma. Due to an androgen-directed rise of CBG, large amounts of plasma cortisol were detected. However, preoperative SBP capacity was found to be reduced. The steroid profile of cyst fluids was found to be similar to that of peripheral plasma. Neoplastic cells were found capable of producing an androgen binding protein. These results correlated well with Sertoli-Leydig cell tumors histology, i.e. a testis-like endocrine structure. From the endocrine profile, the steroid biosynthetic pathways are discussed with respect to the possibility that biosynthesis, once the 17-OH-pregnenolone structure was reached, was active along both the delta 5 and delta 4-steroid pathways. The steroid levels in tumor vein and their corresponding gradients to the periphery are discussed with respect to: i) the possibility of metabolic and biosynthetic capacities of cancer cells bearing an undifferentiated steroidogenic appearance, ii) the possibility for tumor steroid secretion by others means than by venous blood and iii) the possibility that both point i) and ii) could be the cause of inconsistent diagnosis significant of endocrine profile as observed in some patients.

Adolescent↗

PubMed1990

Growth hormone (GH) secretory dynamics in animals administered estradiol utilizing a chemical delivery system.

We have utilized a redox chemical delivery system (CDS) for the brain targeting of estradiol (E2) to ascertain its effects on GH secretory patterns in adult intact male rats. The E2-CDS (1.0 mg/kg) dissolved in 20% hydroxypropyl-cyclodextrin (HPCD), E2 (1.0 mg/kg) alone in 20% HPCD, or 20% HPCD was administered intravenously. GH secretory profiles, plasma steroid levels, and anterior pituitary levels of hormones were determined 1 week following steroid injection. Whereas E2 in HPCD and HPCD treatment did not alter masculine GH secretory patterns, animals administered the E2-CDS displayed disrupted GH patterns with attenuated individual pulse amplitudes and significantly elevated GH baseline levels. Moderate pituitary hyperplasia was evident only in the E2-CDS group of animals. Plasma testosterone (T) concentrations were reduced in only the E2-CDS group. T replacement reduced E2-CDS-associated pituitary hyperplasia and preserved the masculine GH secretory profiles, with only a slight reduction in individual GH peak amplitudes being observed. T replacement did not prevent the increase in pituitary and plasma levels of PRL associated with E2-CDS treatment but did block both the increase in pituitary GH content and the hyperplasia associated with prolonged E2 exposure. E2 given alone induced a significant increase in both GH and PRL in the pituitary without establishment of pituitary hyperplasia or elevated plasma PRL levels. These data indicate that E2-CDS is an effective mode of steroid administration. Changes in GH secretory dynamics, pituitary levels of GH, and degree of hyperplasia are dependent upon the chemical design of the delivery system for E2. Concomitant T therapy can prevent some of the changes in GH secretion associated with high-dose E2 exposure.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1982

Fecal cholesterol excretion studies in type II hypercholesterolemic patients treated with the soybean protein diet.

The fecal steroid elimination profile was studied in 7 type II hyperlipoproteinemic patients given a low-lipid diet with textured soybean proteins, in order to define the mechanism of the hypocholesterolemic activity of this new dietary regimen. Four of the patients followed a 3- + 3-week cross-over protocol, comparing the soybean diet with a reference low-lipid diet with animal proteins. In these, fecal neutral steroids and bile acids were analyzed by chromatography during the two dietary periods. In spite of the clear hypocholesterolemic effect, no significant differences in steroid output were noted between the two dietary periods. In the 3 remaining patients, a chromatographic + isotopic method (by injecting 14C-labelled cholesterol i.v. 4-6 weeks prior to the dietary study) was employed. Again, no marked changes were noted in the fecal neutral steroid and bile acid outputs and the slope of the decay curve of the plasma cholesterol-specific activity was not changed by the experimental diet, in spite of the remarkable decrease in plasma cholesterol. The reported results do not provide a definitive contribution to the mode of action of the soybean protein diet. They suggest, however, that it is not an effect mediated by undigestible dietary components. The possibility of a cholesterol redistribution from plasma to tissue pools should be considered.

Bile Acids and Salts↗

PubMedDate not supplied

[Immune sexual dimorphism: can sex steroids affect the Th1/Th2 cytokine profile?].

Cytokine secretion is a crucial aspect in immune system modulation. The secretion pattern of these molecules determines the immune response type that will confront a particular antigen, and this pattern can be at least of two types. A Th1 pattern, effective to eliminate mainly intracellular pathogens and a Th2 pattern, crucial to eradicate extra cellular pathogens. There are many immunological factors that affect expression of these proteins and auto regulate the Th1/Th2 balance, but there are few evidences about effect of other protagonists of mammals physiology. This review focuses on the regulation of the Th1/Th2 cytokine secretion pattern of immune cells by sexual steroids. The evidences indicate that cytokines and steroids form a common chemical language effective to keep the balance between immune and endocrine systems. Alterations of this delicate network can explain different pathologies where gender-associated differences exist and where sexual steroids are crucial factors.

Cytokines↗

PubMed1980

Prediction of tumor response to endocrine therapy in prostatic carcinoma based on steroid receptor assay.

Measurement of estrogen receptor content in human breast cancer has become a valuable tool to predict the response of a tumor to endocrine manipulations. The aim of this study was to see whether steroid receptor assay could also be used to predict the value of endocrine therapy in human prostatic carcinoma. Biopsies from 25 primary tumors were analyzed with regard to quantity of methyltrienolone (a synthetic androgen) binding to the receptor 20 specimens were receptor-positive and 5 were receptor-negative. The correlation between receptor content and response to endocrine treatment was approximately approximately equal to 80%. The steroid receptor profiles of 5 lymph node metastases were also analyzed. 4/5 contained methyltrienolone receptors and 2/5 contained progestin receptors. 3/5 were glucocorticoid receptor-positive while all specimens were estrogen receptor-negative.

Hormones↗

PubMed2000

Maternal drug abuse and human term placental xenobiotic and steroid metabolizing enzymes in vitro.

We evaluated the impact of maternal drug abuse at term on human placental cytochrome P450 (CYP)-mediated (Phase I) xenobiotic and steroid-metabolizing activities [aromatase, 7-ethoxyresorufin O-deethylase (EROD), 7-ethoxycoumarin O-deethylase (ECOD), pyrene 1-hydroxylase (P1OH), and testosterone hydroxylase], and androstenedione-forming isomerase, NADPH quinone oxidoreductase (Phase II), UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST) activities in vitro. Overall, the formation of androstenedione, P1OH, and testosterone hydroxylase was statistically significant between control and drug-abusing subjects; we observed no significant differences in any other of the phase I and II activities. In placentas from drug-abusing mothers, we found significant correlations between ECOD and P1OH activities (p < 0. 001), but not between ECOD and aromatase or P1OH and EROD activities; we also found significant correlations between blood cotinine and UGT activities (p < 0.01). In contrast, in controls (mothers who did not abuse drugs but did smoke cigarettes), the P1OH activity correlated with ECOD, EROD (p < 0.001), and testosterone hydroxylase (p < 0.001) activities. Our results (wider variation in ECOD activity among tissue from drug-abusing mothers and the significant correlation between P1OH and ECOD activities, but not with aromatase or EROD activities) indicate that maternal drug abuse results in an additive effect in enhancing placental xenobiotic metabolizing enzymes when the mother also smokes cigarettes; this may be due to enhancing a "silent" CYP form, or a new placental CYP form may be activated. The change in the steroid metabolism profile in vitro suggests that maternal drug abuse may alter normal hormonal homeostasis during pregnancy.

Adult↗

PubMed2004

Excretion of urinary steroids in pre- and postpartum female baboons.

Steroid hormones are important regulators of a wide variety of reproductive and behavioral functions. We investigated the ability to track sex steroids and glucocorticoids in urine samples collected noninvasively from pre- and postpartum female baboons. Paired plasma and urine samples were collected every 2 weeks prior to and following birth in 10 females. Changes in concentrations of plasma steroids (estradiol, progesterone, and cortisol) were reflected in changes in urinary metabolite excretion (estrone conjugates, pregnanediol conjugates, and cortisol; r's>0.36, p's<0.001). A low correlation between prepartum plasma and urinary cortisol may reflect late-gestational changes in the production and/or metabolism of glucocorticoids. Steroid excretion profiles in a large sample of females giving birth and caring for healthy infants (n = 108) were compared with profiles obtained from females with poor maternal-fetal outcomes (late-term stillbirth, n = 14) and from females with significant postpartum problems with maternal care (n = 20). Mothers giving birth to stillborn infants had lower prepartum levels of urinary estrone conjugates and cortisol, suggesting reduced placental steroidogenesis. Mothers with postpartum behavioral difficulties had higher concentrations of prepartum estrone excretion, lower cortisol excretion, and elevated E/P ratios throughout the peripartum period. Noninvasive sample collection and enzyme immunoassay, therefore, have predictive utility regarding circulating steroid concentrations and can identify important endocrine correlates of physiological and behavioral abnormalities in baboons.

Animals↗

PubMed2005

Steroid receptor expression in late follicular phase endometrium in GnRH antagonist IVF cycles is already altered, indicating initiation of early luteal phase transformation in the absence of secretory changes.

BACKGROUND: Ovarian stimulation for IVF profoundly alters the early luteal phase endometrial development. It has been hypothesized that this process has already started in the late follicular phase, as the endometrium has already been exposed to high steroid concentrations since that phase. The aim of the present study was to prospectively investigate the effect of multi-follicular ovarian stimulation for IVF on the late follicular phase endometrium histology and the expression of estrogen receptor (ER) and progesterone receptor (PR). METHODS: In a cross-over study, 11 infertile women with normal ovulatory function, participating in an IVF programme and treated with GnRH antagonist/recombinant FSH ovarian stimulation, were enrolled in the study. Endometrial biopsies were taken in a natural cycle on the day of the onset of the surge of the LH, and in a subsequent stimulation cycle on the day of hCG administration for final oocyte maturation. Endometrial histological dating was carried out according to Noyes' criteria. Immunohistochemistry was performed, using commercially available antibodies for ER and PR endometrial expression. The immunohistochemical signal was recorded in 1000 epithelial cells in each compartment (glands and stroma). Endometrial expression for each of the two receptors was graded on a scale of 0-3, based on the intensity of nuclear staining. Then a score range between 0 and 3000 was recorded, and expressed as a mean score per 1000 stroma or glandular cells per sample (range: 0-3). RESULTS: Histological examination of biopsies both in natural and stimulated cycles showed no secretory changes. However, in stimulated cycles, PR expression was significantly up-regulated compared to natural cycles in both glands (1.67 versus 1.34, P < 0.05) and stroma (1.98 versus 1.62, P < 0.05), whereas ER was down-regulated in glands (1.15 versus 1.43, P < 0.05). In IVF cycles, the progesterone measurements, although within normal values (range 0.8-1.4 microg/l), were significantly higher than in natural cycles (0.99 vs 0.63 microg/l, respectively, P = 0.008). An ongoing pregnancy rate of 37.5% was achieved in the stimulated cycles. DISCUSSION: Although the current study found no early secretory transformation in stimulated endometria before hCG administration, the ER and PR expression in these endometria is similar to the one described during the first days of the luteal phase in natural cycles. Supraphysiological concentrations of estradiol and subtle progesterone rises in the late follicular phase might be responsible for this modulated steroid receptor profile. This phenomenon indicates accentuated maturation of the endometrium in IVF cycles from the pre-ovulatory phase onwards.

Adult↗

PubMed1997

Differential effects of flavonoids on testosterone-metabolizing cytochrome P450s.

Flavonoids are widely distributed phytochemicals, whose modulation of cytochrome P450 mediated carcinogen metabolism is well established. Less well studied is their effect on P450 dependent metabolism of endogenous substrates. To address this question we evaluated a series of twelve flavonoids and hematoxylin for their effect on P450-mediated steroid hydroxylation by rat liver microsomes. Site-specific 7alpha-, 6beta- and 2alpha-hydroxylation of testosterone by P450s 2A1, 3A2 and 2C11, respectively, was measured. Highly selective patterns of inhibition or activation of these P450s were observed. 3,6-dichloro-2'-isopropyloxy-4'-methylflavone was the most potent inhibitor of P450 2C11 while cyanidin chloride most potently inhibited P450s 2A1 and 3A2. The flavonoid analogue hematoxylin was unique in that it activated 2C11 (by 2.5 fold) yet inhibited both 2A1 and 3A2 (by 60%). These results indicate that consumption of dietary flavonoids may likewise alter the metabolite profile of steroids and other physiological P450 substrates.

Animals↗

PubMed1987

Changes in the secretion of inhibin and steroid hormones during induced follicular atresia after hypophysectomy in the rat.

Sequential changes in the function of antral follicles during the period of follicular atresia were investigated after hypophysectomy (Hypox) at 1100 hr on proestrus. Within 6 hours after Hypox, concentrations of progesterone (P), testosterone (T) and estradiol-17 beta (E) decreased abruptly in ovarian venous plasma (OVP) and follicles showed a reduced ability to ovulate. Six hours after Hypox, ovulation was still induced by human chorionic gonadotropin (hCG) in all animals but with significantly fewer number of oocytes compared to the group given hCG at 1100 hr on the day of proestrus. Nine hours after Hypox, several granulosa cells of all large follicles (greater than 400 microns in diameter) exhibited morphological signs of atresia. Twelve hours after Hypox, all large and medium sized (200-400 microns in diameter) follicles showed advanced stages of atresia and almost all follicles failed to ovulate in response to hCG. Inhibin activity in OVP declined more slowly compared to the profiles of steroid hormones and 53% of the initial inhibin activity was still maintained at 18 hours after the operation. Inhibin activity further decreased to 7% of the initial level at 24 hours and was undetectable by 48 hours after Hypox. These results suggest that fully developed Graafian follicles gradually lose their ability to secrete inhibin in contrast to the rapid decrease in secretion of steroid hormone during the process of atresia.

Animals↗

PubMed1994

The evolution of hormonal sex pheromones in teleost fish: poor correlation between the pattern of steroid release by goldfish and olfactory sensitivity suggests that these cues evolved as a result of chemical spying rather than signal specialization.

It is becoming increasingly evident that many teleost fish use hormones and their metabolites as sex pheromones. Although hormonal pheromone systems of several species of fish have now been characterized, that of the goldfish is the best understood. Reproductively-active female goldfish sequentially release derivatives of three steroidal hormones and two prostaglandins which have specific and potent actions on the goldfish olfactory sense and subsequently conspecific reproductive behaviour and physiology. Three goldfish hormonal pheromones are unmodified sex hormones which are also found in the blood of many other species of fish and are therefore unlikely to be species-specific. This scenario evokes two related questions. First, how did these systems evolve? Second, do hormonal pheromones represent specialized signals used for communication or rather simple metabolites which fish have evolved the ability to detect because of their intrinsic meaning ('spying')? Here we review hormonal pheromone function in fish and then describe a study of the goldfish which tests whether hormonal pheromones are specialized communicatory signals by comparing the profile of steroids released by goldfish with their olfactory responsiveness to these compounds. Little correlation between signal production and detection was found and we conclude that the goldfish hormonal pheromone system most likely exemplifies spying.

Animals↗

PubMed1997

Estrogen replacement therapy decreases hyperandrogenicity and improves glucose homeostasis and plasma lipids in postmenopausal women with noninsulin-dependent diabetes mellitus.

Hyperandrogenicity in women is closely associated with insulin resistance and a risk factor for cardiovascular disease and noninsulin-dependent diabetes mellitus (NIDDM). Therefore, 25 postmenopausal women with NIDDM and sex hormone-binding globulin values less than 60 nmol/L, as an indicator of a moderate hyperandrogenicity, were treated with 2 mg 17-beta-estradiol orally for 3 months in a double-blind, cross-over, placebo-controlled trial. During the last 16 days of active treatment, 1 mg norethisterone acetate was added for 10 days for endometrial protection. Blood glucose, glycosylated hemoglobin, insulin, c-peptide, lipoprotein profile, sex steroid hormones, GH, and insulin-like growth factor I (IGF-I) were measured, and insulin sensitivity was determined by the euglycemic hyperinsulinemic clamp method. All metabolic measurements were taken at baseline and after 68 days of active or placebo treatment. Estradiol treatment, compared with the placebo period, was followed by a marked increase of sex hormone-binding globulin and a decrease of free testosterone. Blood glucose, glycosylated hemoglobin, c-peptide, total cholesterol, low-density lipoprotein cholesterol, and IGF-I decreased significantly (P < 0.01-P < 0.001), whereas high-density lipoprotein cholesterol rose (P < 0.001). In conclusion, estrogen replacement therapy in postmenopausal women with NIDDM ameliorated hyperandrogenicity, and this was accompanied by marked improvements in glucose homeostasis and lipoprotein profile.

Androgens↗

PubMed1990

Binding proteins for insulin-like growth factors in the human ovary: identification, follicular fluid levels and immunohistological localization of the 29-32 kd type 1 binding protein, IGF-bp1.

The occurrence of pregnancy-associated endometrial alpha 1-globulin (alpha 1-PEG), a 29-32 kd insulin-like growth factor binding protein, now termed type 1 or IGF-bp1, has been examined in the human ovary by monoclonal and polyclonal antibody based radioimmunoassay and immunohistological techniques. Follicular fluids aspirated from 51 follicles of 32 women undergoing hyperstimulation involving buserelin or clomiphene-based protocols contained 35.5-276.0 ng/ml (mean 101.0 mg/ml) of immunoreactive IGF-bp1. Mean fluid concentrations were three times the level of IGF-bp1 detected in paired serum samples, available for 21 women. Immunoreactive IGF-bp1 in follicular fluid exhibited similar dose-response curves to purified protein and amniotic fluid and immunoreactive IGF-bp1 coeluted in gel filtration with a peak of [125I]-IGF-1 binding corresponding to the elution profile of purified IGF-bp1. Gel filtration also revealed the presence in follicular fluid of a greater than 100 kd binding protein with a binding capacity equal to IGF-bp1 under the conditions employed. A highly significant correlation (P less than 0.001) was found between follicular fluid progesterone and IGF-bp1 and a correlation of lower significance was found between oestradiol and IGF-bp1 (P less than 0.05). However, only low levels of immunoreactive IGF-bp1 were detected in supernatant media of granulosa cells in culture (range undetectable to 2.3 ng/ml). Employing monoclonal antibody-based immunohistology, immunoreactive IGF-bp1 was consistently associated with luteinized granulosa cells of corpora lutea rather than paraluteal cells and its intensity of reactivity appeared to reflect luteal phase steroid hormone profiles. No consistent reactivity was detected in preovulatory follicles and granulosa cells in culture, although reactivity was associated with primordial oocytes. Immunoreactive IGF-bp1 was detected in six of nine supernatant media of explants of luteal tissue obtained from five corpora lutea, with levels ranging from undetectable to greater than 200 ng/ml. These observations suggest that IGF-bp1 is primarily related to luteinization of the granulosa and the resultant luteal cells, and if produced by the luteal cells, additional exogenous factors are required to induce production by granulosa cells in vitro.

Adult↗

PubMed1997

Effects of ursodeoxycholic acid on conjugated bile acids and progesterone metabolites in serum and urine of patients with intrahepatic cholestasis of pregnancy.

BACKGROUND/AIMS AND METHODS: The mechanism(s) behind the effects of ursodeoxycholic acid on serum steroid sulphate profiles in patients with intrahepatic cholestasis of pregnancy is not clear. Conjugated progesterone metabolites and bile acids have therefore been analysed in serum and urine of patients with intrahepatic cholestasis of pregnancy before and during treatment with ursodeoxycholic acid using chromatographic and mass spectrometric methods. RESULTS: The concentration of glycine-/taurine-conjugated bile acids decreased from 8.9+/-3 micromol/l (mean+/-SEM) before treatment to 1.8+/-0.6 micromol/l during treatment with ursodeoxycholic acid. The total bile acid excretion in urine decreased from 56+/-14 to 32+/-5.6 micromol/g creatinine. The proportion of cholic acid in serum and urine, and of 1beta-, 2beta- and 6alpha-hydroxylated cholic acids in urine decreased markedly during ursodeoxycholic acid while the percentages of 3alpha,12alpha-dihydroxy-3-oxo-4-cholenoic acid and chenodeoxycholic acid were unchanged. The levels in serum and excretion in urine of sulphated steroids decreased during ursodeoxycholic acid, by 45-49% for disulphates and 33-35% for monosulphates. The ratios of 3alpha- to 3beta-hydroxysteroid disulphates were lowered by ursodeoxycholic acid from 1.1 (mean) to 0.68 in serum, and from 1.2 to 0.70 in urine. The corresponding ratios for monosulphates before and during ursodeoxycholic acid were 6.9 and 4.5, respectively, in serum, and 21 and 5.2, respectively, in urine. The major monosulphates in urine, dominated by 5alpha-pregnane-3alpha, 20alpha-diol, were also conjugated with N-acetylglucosamine. The excretion of these double conjugates decreased from 27+/-8.4 to 15+/-5.3 micromol/g creatinine during ursodeoxycholic acid. In contrast to sulphated steroids, the concentrations of glucuronides were unchanged in serum and their excretion in urine tended to increase during ursodeoxycholic acid. The metabolism of ursodeoxycholic acid was similar to that described in nonpregnant subjects. In addition to metabolites hydroxylated in the 1beta-, 5beta-, 6alpha/beta and 22-positions, a 4-hydroxy-ursodeoxycholic acid was tentatively identified. This occurred predominantly as a double conjugate with glycine/taurine and glucuronic acid, as did other 4-hydroxylated bile acids of probable foetal origin. CONCLUSIONS: The results are compatible with the contention that ursodeoxycholic acid stimulates the biliary excretion of sulphated progesterone metabolites, particularly those with a 3alpha-hydroxy-5alpha(H) configuration and disulphates. The effect(s) appears to be independent of the stimulation of bile acid secretion. An effect of ursodeoxycholic acid on the reductive metabolism of progesterone cannot be excluded.

Bile Acids and Salts↗

PubMed1994

Structural determinants of cytochrome P450 2B1 specificity: evidence for five substrate recognition sites.

Twelve site-directed mutants of rat cytochrome P450 2B1 distributed over seven positions and four putative substrate recognition sites (SRS) were constructed and expressed in COS cells. Function was examined using androstenedione and testosterone as substrates. Substitutions at positions 303, 360, and 473 did not markedly affect the regio- or stereoselectivity of androgen metabolism, whereas mutants in positions 206 (SRS-2), 302 (SRS-4), and 363 and 367 (SRS-5) exhibited markedly different steroid metabolite profiles compared with parental P450 2B1. In particular, the Phe-206-->Leu substitution conferred androgen 6 alpha- and testosterone 7 alpha-hydroxylase activities, and the Thr-302-->Ser substitution suppressed androgen 16 beta-hydroxylation in favor of androstenedione 16 alpha- and testosterone 15 alpha-hydroxylation. Replacement of Val-363 or Val-367 with Ala conferred androgen 15 alpha-hydroxylase and 6 beta-hydroxylase activities, respectively, and suppressed susceptibility to mechanism-based inactivation by the P450 2B1-selective chloramphenicol analog N-(2-p-nitrophenethyl)chlorofluoroacetamide. The Val-367-->Ala mutant was also resistant to chloramphenicol itself. The Leu mutant at position 363 exhibited increased specificity for androstenedione and testosterone 16 beta-hydroxylation, whereas the Leu mutant at position 367 exhibited decreased stereospecificity. Most interestingly, the size of key residues identified plays a critical role in governing steroid hydroxylation from the alpha-face or beta-face and hydroxylation on the D-ring or the B-ring.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed2004

Self-efficacy predicts self-reported health status in multiple sclerosis.

Self-efficacy is a belief that one can competently cope with a challenging situation. If self-efficacy is a strong predictor of health status in multiple sclerosis (MS), it may be an important area to target in clinical practice, as such beliefs may be modifiable. The aim of this study was to examine the predictive value of self-efficacy on self-reported health status in MS. Eighty-nine people with MS completed the Multiple Sclerosis Self-efficacy Scale (MSSE function and control scales), the Multiple Sclerosis Impact Scale (MSIS-29), and the Multiple Sclerosis Walking Scale (MSWS-12) at two time points: 1) admission to an inpatient rehabilitation unit (n = 43) or for steroid treatment for relapses (n = 46); and 2) discharge (rehabilitation group) or six weeks later (steroid group). Multiple regression analyses examined whether baseline and changes in self-efficacy predict changes in self-reported health status. Both baseline and changes in self-efficacy were strong and independent predictors of changes in health status (P-values ranged from 0.025 to < 0.001). That is, pretreatment self-efficacy scores and increases in self-efficacy scores from baseline to follow-up (improvement), were significantly associated with decreases (improvement) in perceived walking ability and physical and psychological impact of MS. The findings suggest that self-efficacy predicts improvement in health status and that self-efficacy would be an important domain to measure and manage actively in education and rehabilitation programs.

Adult↗

PubMedDate not supplied

Relation between the hormonal and epidemiological aspects of ovarian cancer patients in Japan.

We compared the hormonal and epidemiological aspects of ovarian cancer patients in search of the etiology of this neoplasia. Case-control studies of Japanese women with and without cancer were conducted in parallel, with regard to both the excretion of 14 urinary steroids and the pertinent physical and physiological parameters. The results obtained are as follows: 1) premenopausal ovarian cancer patients before and after radical ovariectomy and postmenopausal-postoperative patients were associated with a specified steroid deviation profile characterized by a combination of general depression of androgens, progestins and corticosteroids with sole rescue of tetrahydrocortisol (THF) in urine. 2) The deviation profile of postmenopausal-preoperative cancer patients was distinguished from the 3 partner profiles by its preservation of normalcy in the excretions of androgen and progestin in urine. 3) Ovarian cancer patients were associated with growth retardation, when compared with urban healthy controls and patients with either breast cancer or endometrial cancer by the age-matching method. Ovarian cancer patients were also less fertile than age-matched normal controls, and were as infertile as age-matched patients with either breast cancer or endometrial cancer. 4) Epidemiological evidence was presented to suggest that the incidence of ovarian cancer in Japan was increasing in parallel with the recent increase of social tension in Japan. The possible relevance of the hormonal characteristics of ovarian cancer patients to both the epidemiological characteristics of the same cancer patients and the genesis of this neoplasia is discussed in the light of the 2-step carcinogenesis theory.

Body Height↗