17-ketosteroids and Osteoporosis

17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) mainly catalyze the reduction of C17-ketosteroids to their corresponding hydroxylated forms as well as the reverse reaction (oxidation). Able to convert inactive or less active steroid hormones into more potent ones and vice versa, certain 17beta-HSDs play a key role, especially in the regulation of estrogen and androgen levels. The therapeutic potential of this enzyme family, especially for the treatment of breast cancer, prostate cancer, acne and osteoporosis, then stimulated the development of inhibitors of 17beta-HSDs and important progress was achieved over the last years.. This review article reports all patent applications related to the inhibitors of 17beta-HSDs, including some articles needed to complement the information presented.. Readers will be informed about the role and function of 17beta-HSDs in the first section and about the history of inhibitor development in the second section. Furthermore, in the third and main section, the readers will learn about the structures of patented inhibitors originating from different companies and academic groups.. The increase in the number of 17beta-HSD inhibitors reported in the last years augurs well for the future. The challenge is now to translate these results into clinical studies to allow determination of the therapeutic usefulness of 17beta-HSD inhibitors.

Topics: 17-Hydroxysteroid Dehydrogenases; 17-Ketosteroids; Acne Vulgaris; Animals; Clinical Trials as Topic; Drug Design; Enzyme Inhibitors; Humans; Neoplasms; Osteoporosis; Patents as Topic

Professor Urist's contributions to the understanding of osteoporosis are worthy of reevaluation at this time, when interest in the field has reached unprecedented heights. Recent advances in technology have greatly increased our understanding of osteoporosis by showing that there is no loss of bone in normal premenopausal women, and that the loss which starts at the menopause can be attributed to an increase in bone resorption. It is suggested that the primary event is a rise in plasma calcium that leads to a rise in obligatory urinary calcium loss, which in turn increases the calcium requirement. The subset of the postmenopausal population who develop fractures (particularly in the spine) show additional risk factors, which include malabsorption of calcium (which further increases bone resorption) and reduced adrenal androgen production (which may produce a fall in bone formation). The treatment of established cases requires control of bone resorption by calcium supplementation and/or hormone therapy, with the addition of calcitriol if malabsorption of calcium is present. Stimulation of bone formation is more difficult, but there is a suggestion that this may be possible with the use of anabolic steroids.

Topics: 17-Ketosteroids; Androgens; Bone and Bones; Bone Resorption; Calcitonin; Calcitriol; Calcium; Calcium, Dietary; Estrogens; Female; Humans; Intestinal Absorption; Male; Menopause; Minerals; Osteogenesis; Osteoporosis; Parathyroid Hormone; Progestins; Risk; Skinfold Thickness; Sodium

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adolescent; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Adult; Body Constitution; Cushing Syndrome; Dehydroepiandrosterone; Dexamethasone; Ecchymosis; Female; Hemorrhagic Disorders; Humans; Hydrocortisone; Male; Osteoporosis; Periodicity; Pneumoperitoneum, Artificial; Proteins; Radiography

The purpose of the study was to analyse bone density in patients with noninsulin-dependent diabetes mellitus with respect to such factors as the magnitude of obesity, serum cortisol concentration and 17-ketosteroid excretion and insulinemia level. Bone density was measured by ultrasonography, insulin was determined by radioimmunoassay, and steroid level by using the method of Zimmerman. The patients had imminent and overt osteoporosis. The highest serum cortisol concentration was in groups with lower T-score significant negative correlation between cortisol and SOS index. The lowest 17-ketosteroid level was detected in the patients with the lowest T-score; a significant correlation was observed between 17-ketosteroids and BUA index. The present findings indicate an imbalance between bone protective and resorptive factors. This leads to osteopenia in patients with noninsulin-dependent diabetes mellitus despite a protective effect of obesity.

Topics: 17-Ketosteroids; Aged; Body Mass Index; Bone Density; Diabetes Mellitus, Type 2; Female; Humans; Hydrocortisone; Male; Middle Aged; Obesity; Osteoporosis

Results of a dynamic roentgenological (100 patients aged 33 to 89 years), and roentgeno-pathomorphological examination of the osteoarticular apparatus in persons suffering from post-climacteric spondylopathy are presented. A comparison of those results with the clinical and laboratory findings, as well as with similar changes occurring in a number of other diseases showed that it was osteoporosis that underlay the pathological process. The osteoporosis was prevalent in the vertebral column, and led to a vertebrodiscal dissociation that caused a pathological reconstitution of the vertebral bodies. Depending on the degree of the osteoporosis and the vertebrodiscal dissociation, and with consideration of the clinical findings initial manifestations of three stages of the disease have been specified. The use of sex hormones, drugs of the type of retabolil and nerobol that diminish the anabolic insufficiency, as well as of vitamin D, rational diets, insolation, a relief of the vertebral column with the aid of a corset; therapeutic exercises and massage make it possible to arrest the pathological process.

Topics: 17-Ketosteroids; Adult; Aged; Climacteric; Female; Humans; Intervertebral Disc; Male; Middle Aged; Osteoporosis; Spinal Diseases; Testosterone; Vaginal Smears

To explore the possibility that the wide variation in bone loss among oophorectomised women might be due to differences in adrenal androgens or their biosynthetic pathways, 18 women (10 with very fast and 8 with very slow bone loss) were selected. Serum levels of nine adrenal steroids, including the major androgens and cortisol, were measured under basal conditions and after overnight suppression followed by acute corticotropin stimulation. In addition, basal serum oestrone, oestradiol, dehydroepiandrosterone sulphate, sex-hormone-binding-globulin, corticosteroid binding globulin, and urinary free cortisol were measured. The only significant differences found were that women who lost bone rapidly had significantly higher urinary free-cortisol excretion (p less than 0.001) and a paradoxically diminished cortisol response to corticotropin. These data make it unlikely that endogenous adrenal androgens or oestrogens are a major factor in preventing bone loss after cessation of ovarian function; cortisol by its catabolic effect, however, may be a significant factor in causing osteoporosis.. To examine the influence of differences in adrenal androgens or their biosynthetic pathways in the wide variations in bone loss among oophorectomized women, 18 women were selected for study. 10 women had very fast bone loss and 8 had very slow; 5 other women who had been on estrogen replacement therapy were also selected. Difference between the fast and slow losers in urinary free cortisol excretion was highly significant; the levels were higher in fast loser (P-.001). Treated patients had values similar to those of slow losers. No difference was detected between fast and slow losers in basal plasma values for dehydro-epiandrosterone (DHEA), adione, adiol, testosterone, DHEA-SO4, estrone, estradiol, cortisol, sex hormone binding globulin, and corticosteroid binding globulin. The only significant differences found were that women who lost bone rapidly had significantly higher free cortisol excretion and a paradoxically diminished cortisol response to corticotropin. It is, therefore, unlikely that endogenous adrenal androgens or estrogens are a major factor in preventing bone loss after cessation of ovarian function; however, cortisol, because of its catabolic effect may be a significant factor in causing osteoporesis. The serum levels of the 9 adrenal steroids were measured under basal conditions and after overnight suppression followed by acute corticotropin stimulation.

Topics: 17-Ketosteroids; Adult; Androgens; Androstenediols; Androstenedione; Castration; Dehydroepiandrosterone; Estradiol; Estrogens; Estrone; Female; Humans; Hydrocortisone; Hydroxysteroids; Middle Aged; Osteoporosis; Sex Hormone-Binding Globulin; Testosterone

Topics: 17-Ketosteroids; Follicle Stimulating Hormone; Fractures, Bone; Humans; Hydrocortisone; Hypogonadism; Lumbar Vertebrae; Luteinizing Hormone; Male; Middle Aged; Osteoporosis; Pituitary Gland; Pituitary-Adrenal Function Tests; Testis; Testosterone

Topics: 17-Ketosteroids; Aged; Aging; Blood Protein Electrophoresis; Blood Viscosity; Calcium; Cholesterol; Chronic Disease; Humans; Intracranial Arteriosclerosis; Lipoproteins; Male; Mental Disorders; Middle Aged; Osteoporosis; Stress, Psychological

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adenoma; Adolescent; Adrenal Gland Neoplasms; Adrenal Insufficiency; Adrenalectomy; Adrenocortical Hyperfunction; Adult; Alkaline Phosphatase; Cushing Syndrome; Female; Humans; Hyperostosis Frontalis Interna; Hypothalamic Diseases; Hypothyroidism; Leukocytes; Male; Middle Aged; Neutrophils; Obesity; Osteoporosis

Topics: 17-Ketosteroids; Adrenal Cortex Hormones; Adult; Carbohydrate Metabolism; Cushing Syndrome; Female; Glucocorticoids; Humans; Hypertension; Male; Middle Aged; Osteoporosis

Topics: 17-Ketosteroids; Adult; Ascites; Carcinoma, Hepatocellular; Diabetes Complications; Dwarfism; Female; Glucose Tolerance Test; Humans; Hypogonadism; Islets of Langerhans; Liver Cirrhosis; Liver Neoplasms; Obesity; Osteoporosis; Pleural Effusion; Pneumonia, Lipid; Sella Turcica

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Acromegaly; Aged; Bone Resorption; Calcium; Calcium Isotopes; Feces; Female; Follicle Stimulating Hormone; Growth Hormone; Humans; Hypothyroidism; Iodine Radioisotopes; Male; Middle Aged; Osteoporosis; Phosphorus; Pituitary Irradiation; Thyroid Function Tests

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adrenal Glands; Animals; Calcium; Desoxycorticosterone; Diet; Female; Humans; Male; Middle Aged; Osteoporosis; Ovary; Rats

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adrenocorticotropic Hormone; Adult; Calcium; Diagnosis, Differential; Humans; Hyperparathyroidism; Middle Aged; Osteomalacia; Osteoporosis; Phosphorus; Pituitary-Adrenal Function Tests

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adrenal Gland Neoplasms; Cushing Syndrome; Diabetes Mellitus; Female; Humans; Hyperplasia; Hypertension; Infant; Infant, Newborn; Male; Obesity; Osteoporosis

Topics: 17-Ketosteroids; Adrenal Cortex Hormones; Estrogens; Geriatrics; Hormones; Orthopedics; Osteoporosis; Parathyroid Hormone; Steroids; Surgical Procedures, Operative; Urine

Topics: 17-Ketosteroids; Androsterone; Body Fluids; Etiocholanolone; Female; Humans; Menopause; Metabolism; Osteoporosis; Osteoporosis, Postmenopausal; Urine

Topics: 17-Ketosteroids; Adrenocorticotropic Hormone; Androsterone; Body Fluids; Etiocholanolone; Female; Humans; Menopause; Metabolism; Osteoporosis; Osteoporosis, Postmenopausal; Pharmacology; Testosterone; Urine

Topics: 17-Ketosteroids; Androsterone; Female; Humans; Menopause; Osteoporosis; Postmenopause; Turner Syndrome

Topics: 17-Ketosteroids; Adrenal Cortex Hormones; Adrenalectomy; Adrenocortical Hyperfunction; Cushing Syndrome; Humans; Hypophysectomy; Osteoporosis; Pituitary ACTH Hypersecretion; Radiography

Topics: 17-Ketosteroids; Adrenocorticotropic Hormone; Biological Transport; Body Fluids; Female; Geriatrics; Humans; Menopause; Osteoporosis; Osteoporosis, Postmenopausal; Pituitary-Adrenal Function Tests; Testosterone; Urine

Topics: 17-Ketosteroids; Adrenocorticotropic Hormone; Anabolic Agents; Androgens; Androsterone; Calcium, Dietary; Cortisone; Deficiency Diseases; Dietary Proteins; Drug Therapy; Estrone; Hormones; Humans; Immunization, Passive; Osteoporosis; Physical Therapy Modalities; Proteins; Steroids; Vitamin D