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At least 577 records · Page 32Linked to original sources
PubMed1992

Steroids, the steroid community, and Upjohn in perspective: a profile of innovation.

The announcement in 1949 at the Mayo Clinic of the dramatic effect of cortisone in alleviating the symptoms of rheumatoid arthritis triggered a competitive worldwide research and development effort directed toward a single goal, the practical synthesis of the rare corticosteroids. The confluence of an extraordinary coalescence of multiple events and circumstances in the growth of the Upjohn Company with the Mayo discovery, inclusive of a pioneering role in the steroid field, conspired to create an environment ripe for innovation. The breakthrough, which gave Upjohn an early competitive edge, followed with startling swiftness. A common mold of the genus Rhizopus was found to introduce enzymatically an 11 alpha-hydroxyl group directly into the female hormone progesterone, which had just been synthesized from the soybean sterol stigmasterol--a one-step solution to the known multistep alternatives for 11-oxygenation. Retrospective analysis of this event in perspective with other key developments before and after at Upjohn and in the steroid community reveals a striking profile of ongoing innovation. A parallel scenario in kind was repeated at Upjohn a quarter century later. The sister soybean sterol sitosterol was radically degraded microbiologically and concurrently oxygenated in ring C to produce 9 alpha-hydroxyandrostenedione, an alternative key intermediate for corticoid synthesis. New chemical processes, highly integrated with existing processes, assured the continuation of Upjohn's leading role in steroid hormone production.

Cortisone↗
PubMed1997

Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid.

Dienogest is an orally active synthetic steroid that is used for contraception and is currently being studied for the possible treatment of endometriosis. Earlier we demonstrated that dienogest had therapeutic effects on experimental endometriosis in rats and that its mechanisms of action were different from those of drugs currently on the market for the treatment of endometriosis. We also reported preclinically that dienogest showed a potential anticancer action against hormone-dependent cancers that was different from that of progestins. Accordingly, we obtained preclinical background data for the above-described clinical applications and extension of the clinical use of the drug in the near future by investigating the endocrinological profile of dienogest in rabbits and rats. Dienogest was characterized by having a moderate binding affinity for progesterone receptors and by progestational activities: it stimulated endometrial proliferation (> or = 0.01 mg/kg) that was only partially inhibited by RU-486, and induced carbonic anhydrase activity in endometrium (> or = 0.01 mg/kg). Also, it was slightly uterotrophic (> or = 1 mg/kg) with very low binding affinity for oestrogen receptors but without biological androgenic and anabolic activities (100 mg/kg), with neither glucocorticoid activity nor mineralocorticoid activity (100 mg/kg), and with very slight binding affinity for human sex hormone-binding globulin. These findings suggest that dienogest is not a pure progestin and appears to induce fewer side effects than drugs currently on the market for the treatment of endometriosis.

Animals↗
PubMed1989

Dietary influences on cardiovascular disease risk in anabolic steroid-using and nonusing bodybuilders.

Recent studies have described an association between high-risk lipoprotein profiles and anabolic steroid abuse by athletes. However, none have included a comprehensive evaluation of diet as a confounding variable. The risk of cardiovascular disease (CVD) and its associations with drug abuse, dietary patterns, and training regimens were evaluated in 18 steroid-using (SU) and 17 non-steroid-using (NSU; no history of drug use or greater than or equal to 1 year drug-free) male bodybuilders. CVD risk was also evaluated in 10 control males. Fasting serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL) and HDL subfractions 2 and 3, low-density (LDL) and very-low-density (VLDL) lipoprotein cholesterol, apoproteins (APO) A-1 and B, and triglycerides (TG) were analyzed at baseline (greater than or equal to 6 months drug-free) and the peak of steroid self-administration in SU. NSU were tested at similar times. Baseline CVD risk factor ratios (TC/HDL) were elevated (greater than 4.97) in 44% of SU and 24% of NSU. When baseline LDL and HDL values were compared to National Cholesterol Education Program CVD risk guidelines, these percentages stayed the same. At the peak of steroid administration significant changes were observed in LDL (22% increase), HDL (63% decrease), HDL-2 (86% decrease), HDL-3 (54% decrease), and TC/HDL (85% increase). No similar measures were observed among NSU or controls. Diets of all bodybuilders were similar, and included a daily intake of 5739 (+/- 2500) kcal, 324 (+/- 163) g protein, 637 (+/- 259) g carbohydrate, 214 (+/- 109) g fat, 5 (+/- 8) g alcohol, 1413 (+/- 1151) mg cholesterol, and a P/S ratio of 0.6 (+/- 0.3). Significant relationships between dietary fats and serum lipids were observed in the NSU. Polyunsaturated fatty acids were correlated with TG and VLDL (r = 0.69; p = 0.01), and TC/HDL (r = 0.06; p = 0.04). Total fats were correlated with TG (r = 0.57; p = 0.05), HDL-3 (r = -0.62; p = 0.04), and VLDL (r = 0.57; p = 0.05), and saturated fats with HDL-3 (r = -0.59; p = 0.055). Diet was moderately associated with lipoproteins in SU, but steroids had a much greater influence on CVD risk. Despite disease promoting diets NSU had relatively average CVD risk that may be attributed to protective effects of rigorous training.

Adolescent↗
PubMed1987

Modeling of peak profiles. Application to the preparative liquid chromatography of steroids.

The solution of the mass balance equations in liquid chromatography describes the propagation of signals of finite concentration through the column. The general numerical solution requires the prior determination of the partition isotherm. For low solute concentrations, when the isotherm equation can be replaced with a two-term expansion, an analytical solution for the peak profiles is obtained. The theory is applied to predict, as a function of solute concentrations, the elution profiles of two steroids of similar structure, cis- and trans-androsterone, with organic solvents as the mobile phase and buffered silica gel as the stationary phase. At infinite dilution both steroids are well resolved, the trans isomer being eluted before the cis isomer. At high concentrations their adsorption isotherms intercept each other and, for large amounts injected, their elution order is reversed, with marked differences in the elution peak shapes of both steroids.

Adsorption↗
PubMed1996

Personality profile of men using anabolic androgenic steroids.

The present study assessed personality traits in three groups of strength athletes, who self-administered anabolic androgenic steroids (AAS) at the time of testing, had stopped using AAS since at least 6 months, or had never used AAS. The subjects (n = 14/group) completed the Karolinska Scales of Personality, an inventory consisting of 15 subscales measuring traits related to anxiety proneness, extraversion, and aggression-hostility. Current AAS users differed significantly from the other two groups with respect to Verbal aggression. In comparison to subjects with no ongoing AAS exposure (i.e., previous AAS users and drug-free controls), AAS users were also significantly different with respect to Muscular tension, Social desirability, Impulsiveness, and Indirect aggression. On several subscales, the scores of the AAS users were clearly outside the normal range observed in general population. The present results confirm earlier studies that AAS use is associated with enhanced aggressiveness. Our study also suggests that self-administration of AAS might pave the way for disinhibitory psychopathology by amplifying extraversion-related risk factors.

Adult↗
PubMed1990

Clinical profile of a new non-steroidal antiandrogen.

Recently a new non-steroidal antiandrogen (Casodex) has been shown in animal experiments to possess a potent peripheral antiandrogen effect. In patients with advanced prostatic cancer however, this drug is not peripherally selectively active and blocked central brain androgen-receptors results in a rise of luteinizing hormone (LH) and testosterone (T). We treated 18 advanced prostatic cancer patients with 50 mg Casodex daily for a mean period of 42 weeks. There were no complete objective responses but partial responses were seen in a few patients. In 16 patients there was a greater than 50% reduction of pretreatment PSA levels. Endocrine evaluations showed a significant rise in LH, T and oestradiol (E), reaching peak values within the two first months with subsequent lowering of these levels afterwards but without returning to normal. The general tolerance of the drug was good, gynecomastia being the most frequent side-effect. Libido and potency, when present before start of therapy, were maintained in some patients. We conclude that this compound seems as effective as other antiandrogens, but with improved compliance, and shows less side effects in the management of advanced prostatic cancer.

Androgen Antagonists↗
PubMed2001

Longterm beneficial effect of chloroquine diphosphate on lipoprotein profile in lupus patients with and without steroid therapy.

OBJECTIVE: To investigate the influence of chloroquine diphosphate (CDP) alone and in combination with corticosteroids on systemic lupus erythematosus (SLE) lipoproteins. METHODS: Fasting lipid profiles were performed in 60 consecutive female patients with SLE and in 30 controls. All SLE patients had minor disease activity and were divided according to current therapy in 4 groups: No therapy; prednisone (Pred group; < 15 mg prednisone daily); CDP (250 mg daily); and Pred + CDP. RESULTS: There were no significant differences of age, race, and disease duration among SLE groups. All patients had SLEDAI scores < or = 4 and prednisone dose was similar in the 2 groups taking this drug. The CDP group had significantly higher levels of high density lipoprotein cholesterol (HDL-c) levels compared to No therapy group (p < 0.05), which were similar to those detected in healthy controls. In addition, higher levels of HDL-c and lower levels of triglycerides and very low density lipoprotein cholesterol levels (VLDL-c) were detected in Pred + CDP compared to Pred (p < 0.05). CONCLUSION: CDP alone or added to corticosteroid therapy has a beneficial effect in SLE dyslipoproteinemia, particularly in increasing HDL-c levels. Additionally, this drug seems to revert the increased hepatic synthesis of lipoproteins induced by corticosteroids as suggested by the concomitant decrease of triglycerides and VLDL-c levels in SLE patients taking the combined regimen.

Chloroquine↗
PubMed1998

Serum progesterone, oestradiol, luteinizing hormone and prolactin profiles in the female black bear (Ursus americanus).

Identifying steroid and pituitary hormone profiles in the female black bear (Ursus americanus) throughout pregnancy may provide a greater understanding of the reproductive cycle and indicate which hormones are required for implantation. Our objective was to assess endocrine activity in black bears oestrus onset, at oestrus, during pregnancy and after parturition. Serum samples were obtained from 12 captive, 16 uncollared and five radiocollared free-ranging female black bears from March through the end of December and assayed for serum progesterone, oestradiol, luteinizing hormone (LH) and prolactin (PRL). In captive bears, progesterone concentrations were low at days 0-10 after oestrus and increased significantly days 25-35 and 45-52 after oestrus. Oestradiol concentrations were high at oestrus (day 0) and days 4-10 after oestrus and then decreased days 25-35 and 45-52 after oestrus. LH concentrations were not significantly different throughout the sampling period. Changes in PRL concentrations pattern were similar to those of oestradiol, with elevated levels at oestrus and days 4-10 after oestrus, followed by a significant decrease 45-52 days after oestrus. In non-collared free-ranging bears, progesterone concentrations increased gradually after mating with a further significant increase in November-December. Oestradiol concentrations were highest in March (before mating) and in June (during mating) followed by a significant decrease in July (early delay period) and November-December (peri-implantation period). LH concentrations were low until November-December and then increased significantly. PRL concentrations were low in March (before mating), increased significantly during the mating season in June, decreased slightly in July, and were low in November-December (peri-implantation period). In radiocollared free-ranging bears, serum progesterone concentrations were elevated in pregnant bears in December and extremely low in lactating and non-lactating bears in March. Oestradiol levels were slightly higher in pregnant bears in December than in non-lactating or lactating bears in March. PRL concentrations were considerably higher in lactating bears in March than in pregnant bears in December. Our results suggest that: (1) serum progesterone concentrations are low, but detectable during the early delay implantation period and greatly elevated during the peri-implantation period; (2) serum oestradiol concentrations are elevated at oestrus and decline during the delay period; (3) LH may be involved in luteal activation; and (4) the decline of serum PRL concentrations during short days may be necessary for implantation to occur.

Animals↗
PubMed1996

A high prevalence of abnormal personality traits in chronic users of anabolic-androgenic steroids.

OBJECTIVE: (1) To assess the personality profiles of the anabolic androgenic steroid users (AAS) and (2) to determine whether valid premorbid personality traits could be obtained from cross sectional assessment using multisource data. METHODS: The first author became a participant-observer in a group of body builders. An experimental group of body builders who had been using AAS for no more than 18 months (n = 12) was identified. A group of control subjects, each of whom claimed that he did not, and never had, used AAS (n = 12) was also recruited during this period. Key informants played a crucial role in recruiting subjects representative of the AAS and body building communities. An interview schedule based on the Diagnostic and statistical manual of mental disorders (DSM3-R) personality disorder criteria was conducted with each subject. Additional data were obtained from an AAS using informant and significant others including family and friends. RESULTS: The user group was significantly heavier than the control group and showed abnormal personality traits, in contrast to the control group. Personality traits of AAS users before the onset of AAS use, assessed retrospectively, were not different from personality traits of control subjects. There were significant differences between the before and after personality traits in AAS user group. CONCLUSIONS: The results suggest (1) that AAS use is associated with significant disturbances in personality profile, and (2) that these personality disturbances are possibly the direct result of AAS use.

Adolescent↗
PubMedDate not supplied

Cyclosporin A is a hormonal immunomodulator. II. Mouse study.

The present study investigated the effects of hydrocortisone (HCA) and cyclosporin A (CS) on the wet weights of various target tissues and on the plasma levels of 6 steroids and cholesterol (CH) in Swiss mice of both sexes. The effects of CS on the weights of the spleen and forestomach, as viewed from their steroid dependencies in weight change, were different for each tissue and for each sex: CS effect on the male spleen was characterized as a mixture of a major androgenic element and a minor corticosteroid-like element, whereas that on the female spleen was scored as purely androgenic. Similarly, CS effects on the male and female forestomachs were interpreted respectively as estrogenic and androgenic in nature. Both the sole use of HCA (CS-free treatment) and the combined use of HCA and CS (CS-aided treatment) increased plasma testosterone (T) and plasma CH at the expense of other plasma steroids, though minor differences were detectable between the two treatments as regards the deviation profiles of 6 steroids and cholesterol with mice of both sexes. Plasma hydrocortisone (F) in males and plasma estradiol (E2) in females were consistently resistant to the depressing effects of the 2 immunosuppressants. In conclusion, the effect of CS on the mouse immune system, as judged from the response of the spleen, was to create a state of hyperandrogenism in favor of the production of immune unresponsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed2002

Anabolic steroids, testosterone-precursors and virilizing androgens induce distinct activation profiles of androgen responsive promoter constructs.

Different androgens, e.g. virilizing androgens such as testosterone and its precursors as well as synthetic anabolic steroids, respectively, induce diverse biological effects. The molecular basis for this variety in biological actions, however, is not well understood. We hypothesized that this variability of actions may be due to steroid-specific target gene expression profiles following androgen receptor (AR)-activation. Therefore, we investigated androgen receptor dependent transactivation of three structurally different androgen responsive promoter constructs ((ARE)(2)TATA-luc, MMTV-luc, GRE-OCT-luc) in co-transfected Chinese hamster ovary (CHO)-cells as an artificial model simulating different natural target genes. Three virilizing androgens (dihydrotestosterone, testosterone, methyltrienolone), three anabolic steroids (oxandrolone, stanozolol, nandrolone) and two testosterone-precursors of gonadal and adrenal origin (dehydroepiandrosterone, androstenedione) were used as ligands (0.001-100 nM). All steroids proved to be potent activators of the AR. Remarkably, anabolic steroids and testosterone-precursors showed characteristic promoter activation profiles distinct from virilizing androgens with significantly lower (ARE)(2)TATA-luc activation. Hierarchical clustering based on similarity of activation profiles lead to a dendrogram with two major branches: first virilizing androgens, and second anabolics/testosterone-precursors. We conclude that steroid-specific differences in gene transcription profiles due to androgen receptor activation could contribute to differences in biological actions of androgens.

Adjuvants, Immunologic↗
PubMedDate not supplied

Freezing affects the activity and subcellular distribution profile of human placental xenobiotic- and steroid-metabolizing enzymes.

Human placentae from both smoking and non-smoking mothers were examined with respect to the activity and apparent subcellular distribution of cytochrome P-450-linked xenobiotic-and steroid-metabolizing activities. Freezing of the placental sample in pieces before preparing mitochondria and microsomes led to decreases in some catalytic activities and changed the distribution profile of activities between mitochondria and microsomes. Cholesterol side-chain cleavage enzyme and aryl hydrocarbon hydroxylase were especially sensitive to the destructive effect of freezing. Activities in the microsomes were apparently more sensitive to freezing than were those in the mitochondrial fraction. In addition to the destruction of activities by freezing, cross-contamination of microsomes and mitochondria was postulated. Freezing tended to level off the differences between induced and uninduced material. In JEG cells, the specific activities of xenobiotic-metabolizing enzymes were higher in the mitochondrial fraction. In liver biopsy samples the expected, principally microsomal, localization of xenobiotic-metabolizing enzymes was observed. It is suggested that the placenta should be processed fresh at least as far as the postmitochondrial supernatant before freezing to avoid the destructive and cross-contaminating effects of freezing.

Cell Line↗
PubMed1990

So-called fibroepithelial polyps of the vagina exhibiting an unusual but uniform antigen profile characterized by expression of desmin and steroid hormone receptors but no muscle-specific actin or macrophage markers.

The nature of the atypical, often multinucleated stromal cells proliferating in the so-called fibroepithelial polyps of the vagina (FEPV) is obscure. The authors therefore investigated immunohistochemically four polyps of this type with a panel of monoclonal and polyclonal antibodies, including those directed against intermediate filaments, steroid hormone receptors, and macrophage antigens. The authors found that the atypical stromal cells of FEPV expressed vimentin, desmin, and receptors for estrogen and progesterone but lacked all the other markers studied. The homogenous antigen profile strongly suggests that FEPV form a disease entity whose characteristic cells are special hormone-sensitive stromal cells with a myoid component of differentiation. Morphologically similar stromal cells expressing steroid hormone receptors but lacking desmin were found in myxomatoid subepithelial regions of the vaginal wall and the cervix.

Actins↗
PubMed2005

Metabolism of the 16-androstene steroids in primary cultured porcine hepatocytes.

The hepatic metabolism of the 16-androstene steroids was investigated using isolated porcine hepatocytes. This study demonstrated that the liver is capable of producing both phase I and phase II steroid metabolites from 16-androstene steroid precursors. 16-Androstene metabolites were recovered by solid-phase extraction and identified by gas chromatography-mass spectrometry (GC-MS). When 5alpha-androstenone was provided as a substrate, both 3beta- and 3alpha-androstenol were produced as well as a metabolite that showed evidence of hydroxylation. Incubations with the various 16-androstene steroids produced metabolic profiles which suggested that the major role of the liver is phase II conjugation. Sulfoconjugated 16-androstene steroids included androstadienol, 5alpha-androstenone, 3beta-, 3alpha-androstenol, and possibly the hydroxylated metabolite of 5alpha-androstenone. It was determined that hydroxysteroid sulfotransferase (HST) is the likely candidate for the sulfoconjugation of the 16-androstene steroids within the liver. Despite the capacity of the hepatocytes to sulfoconjugate the 16-androstene steroids, the principle metabolites produced from incubations with 5alpha-androstenone, 3beta-, and 3alpha-androstenol were glucuronide conjugates, accounting for approximately 68% of all phase II metabolism. These findings underline the importance of steroid conjugation and suggest that hepatic metabolism of the 16-androstene steroids may influence the levels of 5alpha-androstenone present in the circulation, and thus, capable of accumulating in fat.

Androstenes↗