Cover

Contents

Preface

Role of Mitochondria in Steroidogenesis

Abstract

The Cellular Cholesterol Economy

Cytochrome P450

Mitochondrial Specificity of the Cholesterol Side- Chain Cleavage Reaction

Acute versus Chronic Regulation of Steroidogenesis

Steroidogenic Acute Regulatory Protein

StAR Structure and Mechanism of Action

Disorders of StAR: Classic and Non- Classic Congenital Lipoid Adrenal Hyperplasia

P450scc Deficiency: A Rare New Disease

References

The Physiology and Biochemistry of Adrenarche

Abstract

What Is Adrenarche?

Biochemistry and Enzymology of Adrenarche

What Is the Purpose of Adrenarche?

Conclusions and Future Directions

References

Update on the Corticomedullary Interaction in the Adrenal Gland

Abstract

Evidence from in vitro Studies

Evidence from Animal Models

Evidence from Clinical Observations

Conclusion

Acknowledgement

References

Role of DAX- 1 (NR0B1) and Steroidogenic Factor- 1 (NR5A1) in Human Adrenal Function

Abstract

DAX- 1 (NR0B1)

Steroidogenic Factor- 1 (NR5A1)

Acknowledgements

References

Functional and Physiological Consequences of StAR Deficiency: Role in Lipoid Congenital Adrenal Hyperplasia

Abstract

StAR and Congenital Lipoid Adrenal Hyperplasia

How StAR Stimulates Steroidogenesis

Pathogenesis of Lipoid CAH due to StAR Deficiency

Variabilities in Lipoid CAH Presentation

Conclusions

References

P450 Side- Chain Cleavage Deficiency – A Rare Cause of Congenital Adrenal Hyperplasia

Abstract

Biochemistry

Molecular Genetics and Biology

Clinical Findings in P450scc Deficiency

Practical Summary

References

Clinical and Biochemical Consequences of P450 Oxidoreductase Deficiency

Abstract

Role of Cytochrome P450 Oxidoreductase in the Biochemistry of Electron Transfer

Cytochrome P450s – Partners of POR

Impact of POR Deficiency on Steroidogenesis

Human POR Mutations: From Phenotype to Genotype

Structure and Function Testing of POR Variants in vitro and in silico

POR and Skeletal Malformations

Impact of POR on Drug- Metabolizing P450s

Conclusions and Perspectives

Acknowledgement

References

Molecular Genetics of 21- Hydroxylase Deficiency

Abstract

The CYP21A2 Gene and the RCCX Module

Mutations Causing 21- OHD

Genotype Phenotype Relationships

Molecular Genetic Diagnosis of 21- OHD

References

Brain Development and Cognitive, Psychosocial, and Psychiatric Functioning in Classical 21- Hydroxylase Deficiency

Abstract

Gender Development in 46,XX 21- OHD CAH

Genital Ambiguity, Genital Surgery, and Psychosexual Functioning

Cognitive Development

Psychiatric Development

Notes on 46,XX CAH Raised Male

Conclusions

References

Long- Term Outcome of Prenatal Dexamethasone Treatment of 21- Hydroxylase Deficiency

Abstract

Prenatal Diagnosis and Treatment

Short- Term Outcome of Prenatal Treatment

Long- Term Behavioral Outcome of Prenatally Treated Children at Risk for CAH

Temperament, Psychological Well- Being and Behavioral Problems

Cognition and School Performance

Gender Role Behavior

References

Role of Genetic Variation in Regulation of Aldosterone Biosynthesis

Abstract

Genetic Regulation of Aldosterone Biosynthesis; Understanding Population Cardiovascular Risk

Population Cardiovascular Dysfunction and Aldosterone

Population Variation in Aldosterone Levels

CYP11B1 and CYP11B2

CYP11B Locus and Hypertension

Role of CYP11B1 and CYP11B2 in Genesis of Hypertension

References

Circadian CLOCK- Mediated Regulation of Target- Tissue Sensitivity to Glucocorticoids: Implications for Cardiometabolic Diseases

Abstract

Glucocorticoid Signaling System

The Circadian CLOCK and Its Interactions with the Glucocorticoid Signaling System

Pathophysiologic Implications of the Circadian CLOCK- Mediated GR Signaling System

Concluding Remarks

Acknowledgements

References

Glucocorticoid Resistance

Abstract

Generalized Glucocorticoid Resistance Syndrome

Transient Tissue- Specific Changes in GC Sensitivity

General Population

Conclusion

References

Mineralocorticoid Receptor Gene Variants as Determinants of HPA Axis Regulation and Behavior

Abstract

Corticosteroid Receptors

Genetic Association Studies

MR Gene Variants

In vitro Testing

Neuroendocrine Regulation

Behavioral Traits

Conclusions

Acknowledgements

References

Adrenoleukodystrophy

Abstract

Diagnosis

Pathogenesis

Management and Treatment of Clinical Manifestations

References

Autoimmune Addison’s Disease

Abstract

Primary Adrenocortical Insufficiency

Prevalence of AD

Histopathology

Cellular Immunity

Animal Models

Humoral Immunity

Different Clinical Forms of Autoimmune AD

Genetic and Environmental Factors

The Natural History of Autoimmune AD

Pathogenesis of Autoimmune AD

Diagnosis of Autoimmune AD

Therapy

Acknowledgement

References

Optimal Glucocorticoid Therapy

Abstract

Current Hydrocortisone Therapy in Adrenal Insufficiency

Weight- Related Dosing

Efficacy of Current Hydrocortisone Replacement Therapy

Once- Daily Formulations of Hydrocortisone

Circadian Cortisol Therapy

Disclosure Statement

References

Modulation of Glucocorticoid Metabolism by the GH- IGF- I Axis

Abstract

Interplay between GH, IGF- I and Insulin

Effects of GH on 11β- HSD1

Effects of Insulin on 11β- HSD1

Interplay between the GH- IGF- I Axis and the HSD System in Disease Conditions

Conclusions

References

Effects of Glucocorticoids on the Growth Plate

Abstract

Acknowledgement

References

Growth Hormone Treatment in Children on Chronic Glucorticoid Therapy

Abstract

Disturbance of the GH- IGF- I Axis in CD

Growth Disturbance in JIA

GH Therapy in Children with JIA

Growth Disturbance in CD

GH Therapy in Children with CD

Conclusions

References

Ancient History of Congenital Adrenal Hyperplasia

Abstract

Is There Any Evidence That Pope Joan Existed?

Real Patients That Could Have Been Pope Joan

And Even Before 800 AD

Modern History of CAH

Future of CAH Investigation

Acknowledgement

Suggested Reading

Author Index

Subject Index