Hirsutism

ISBN-13: 9783642815737 / Angielski / Miękka / 2011 / 112 str.

P. Mauvais-Jarvis; F. Kuttenn; I. Mowszowicz

Opis

In the past 10 years hirsutism has been the object of a considerable number of fundamental studies. It provides endocrinologists with an experimental model for the investigation of androgen secretion, metabolism and mechanism of action. Plasma androgen assay, free testosterone measurement, hepatic and extrahepatic androgen metabolic clearance and androgen metabolism in the skin are the different steps which were studied by many groups and represent valuable parameters of the mechanisms of hirsutism. Determination of the origin of androgen oversecretion has become easier by technical progress in differential effiuent venous catheterism, which makes it possible to compare androgens in adrenal or ovarian effiuent veins to their peripheral levels, and to determine the ovarian or adrenal source of the androgen oversecretion as well as the side responsible, essential in the case of tumors. The study of androgen metabolism and the discovery of androgen receptors in the skin confIrm the latter as an actual target cell for androgens. This target cell uses the circulating active androgen, i. e., testosterone and can also metabolize local inactive androgens into active ones. This is the case of androstenedione and dehy droepiandrosterone which are the two main androgens secreted in women, since women secrete very little testosterone. The capacity of the skin to transform inactive androgens into active ones varies from one individual to another. That would support the concept of variable skin receptivity from one woman to another and from one ethnic group to another."

Spis treści

A. Introduction.- B. Androgen Control of the Pilosebaceous Gland.- C. Androgen Production in Women.- I. Definition.- II. Androgen Biosynthetic Pathways.- III. Interconversion of Androgens.- IV. Plasma Levels and Blood Production Rates of Androgens.- V. Origin of Circulatory Androgens in Women.- 1. Testosterone.- 2. Androstenedione.- 3. Dehydroisoandrosterone and Dehydroisoandrosterone Sulphate.- 4. Dihydrotestosterone.- 5. Androstanediols.- VI. Control of Androgen Production in Women.- D. Androgen Transport in Blood.- I. Testosterone-Binding Globulin.- 1. Existence.- 2. Purification of TeBG.- 3. Characterization of TeBG in Serum.- 4. Steroid-Binding Parameters of TeBG.- II. Other Plasma Proteins Binding Androgens.- III. Regulation of TeBG Activity.- IV. Physiological Role of TeBG Binding of Testosterone.- 1. Relationship Between Testosterone Binding and Testosterone Metabolism.- 2. Control of the Oestrogen-Androgen Balance in Women.- 3. Selective Concentration of Active Molecules at the Target Cell Site.- E. Hepatic Metabolism.- F. Control of Plasma Level of Testosterone: Metabolic Clearance Rate.- G. Mechanism of Androgen Action in Human Skin.- I. Introduction.- II. 5?-Reduction of Testosterone into Dihydrotestosterone.- 1. In Vivo Studies.- 2. In Vitro Studies.- a) Biochemical Characterization.- b) Physiological Variations.- c) Control of Testosterone 5?-Reductase in Human Skin.- d) Pathological Models.- e) Studies with Cultured Skin Fibroblasts.- III. Dihydrotestosterone Formation from Other Androgen Precursors.- 1. Androstenedione.- 2. Dehydroisoandrosterone.- IV. Intracellular Metabolism of Dihydrotestosterone.- 1. Physiological Importance of 3?- and 3?-Androstanediols.- 2. Characterization of the 3-Ketoreductases.- V. Intracellular Retention of Dihydrotestosterone.- 1. Methodological Problems.- a) Cultured Fibroblasts.- b) Cell-Free Extracts.- 2. Characterization of the Androgen Receptor.- a) Physiochemical Properties.- b) Heat Lability.- c) Dissociation Constant.- d) Specificity.- 3. Physiological Variations.- 4. Control of Androgen Receptor Concentration.- 5. Pathological Variations.- VI. Conclusion.- H. Clinical and Biological Assessment of Hirsutism.- I. Clinical Assessment.- II. Hormonal Investigation of Hirsutism.- 1. Urinary 17-Ketosteroids.- a) Basal Conditions.- b) Tests of Ovarian Function.- c) Tests of Adrenal Function.- 2. Plasma Androgens.- a) Assays of Testosterone.- b) Assays of Androstenedione.- c) Dynamic Tests for Plasma Testosterone and Androstenedione.- d) Ovarian and Adrenal Vein Catheterization.- e) Dihydrotestosterone.- f) Other Steroids.- 3. Evaluation of Androstanediols.- 4. Conclusion.- I. Hirsutism of Adrenal Origin.- I. Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.- 1. Introduction.- 2. Frequency.- 3. Pathophysiology.- a) General Remarks.- b) Single or Multiple Enzymes.- 4. Androgen Production in 21-Hydroxylase Deficiency.- 5. Clinical and Hormonal Characteristics of Delayed Onset Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.- a) Hormonal Data from the Literature.- b) Personal Data.- c) Interpretation of Results.- 6. Identification of the Heterozygous State.- 7. Genetic Linkage Between 21-Hydroxylase Deficiency and the HLA Blood Group System.- 8. Treatment.- a) Corticosteroid Replacement.- b) Other Treatments.- II. Congenital Adrenal Hyperplasia Due to 11?-Hydroxylase Deficiency.- 1. Pathophysiology.- 2. Clinical Features.- 3. Hormonal Characteristics.- 4. Genetic Transmission.- 5. Treatment.- III. Virilizing Adrenal Tumours.- 1. Pathology.- a) Macroscopy.- b) Histology.- c) Malignant Criteria.- 2. Steroid Production.- a) Dehydroisoandrosterone.- b) Other Androgens.- 3. Clinical Aspects of Virilizing Adrenal Tumours.- a) Adult Females.- b) Prepubertal Females.- 4. Hormonal Findings.- a) Urinary Steroids.- b) Plasma Steroids.- c) Dynamic Tests.- 5. Physical Methods for Diagnosis of Virilizing Adrenal Tumours.- 6. Treatment.- a) Surgical.- b) Chemotherapy.- c) Benign Tumours.- J. Hirsutism of Ovarian Origin.- I. Polycystic Ovarian Syndrome.- 1. Theory of “Hypothalamic Masculinization”.- 2. Two Types of Polycystic Ovaries.- 3. LH-RH Test in the Polycystic Ovarian Syndrome.- 4. Clomiphene Test.- 5. Oestradiol Test.- 6. Androgen Overproduction in Polycystic Ovarian Syndrome.- 7. Pathophysiology of Polycystic Ovarian Syndrome.- 8. Treatment.- 9. Conclusion.- II. Virilizing Ovarian Tumours.- 1. Pathological Classification.- a) Arrhenoblastoma.- b) Hilus Cell Tumours.- c) Lipid Cell Tumours.- d) Granulosa and Theca Cell Tumours.- e) Gonadoblastomas.- f) Functional Stroma Tumours.- g) Luteoma.- 2. Steroidogenesis.- a) Arrhenoblastoma.- b) Hilus Cell Tumours.- c) Luteoma.- 3. Clinical Features.- 4. Hormonal Investigations.- a) Assays in Basal Conditions.- b) Dynamic Tests.- c) Other Methods for Diagnosis.- 5. Differential Diagnosis.- 6. Prognosis.- 7. Treatment.- 8. Conclusion.- III. Ovarian Hyperthecosis.- K. Idiopathic Hirsutism.- I. Basis of Androgen Hypersensitivity.- II. Hypersensitivity Versus Androgen Overproduction.- III. Clinical and Biological Characteristics.- 1. Criteria for Estimation of Androgen Production.- 2. Criteria for Estimation of Peripheral Androgen Consumption.- 3. Personal Data.- a) In Vivo Studies.- b) In Vitro Studies.- e) Interpretation of Results.- IV. Treatment.- V. Conclusion.- L. Treatment of Hirsutism.- I. Introduction.- II. Methods.- 1. Oestrogens.- a) Mechanism of Action.- b) Clinical Use.- 2. Progesterone.- 3. Cyproterone Acetate.- a) Mechanism of Action.- b) Personal Results.- 4. Corticosteroids.- III. Conclusion.- References.