Adrenal Cortex (eBook)

Butterworths International Medical Reviews: Clinical Endocrinology

David C. Anderson, Jeremy S. D. Winter (Herausgeber)

eBook Download: PDF | EPUB

2013 | 1. Auflage
308 Seiten
Elsevier Science (Verlag)
978-1-4831-9211-6 (ISBN)

Infos

Adrenal Cortex presents a critical review of functional and structural zonation of the cortex. It discusses the regulation of adrenocortical function by control of growth and structure. It also addresses the adrenal cortex in the fetus and neonate. It demonstrates the cellular mechanisms involved in the acute and chronic actions of ACTH. Some of the topics covered in the book are the molecular structures of mineralocorticoid and glucocorticoid receptors; description of adrenarche and adrenal hirsutism; types of congenital enzymatic defects of the adrenal; aetiology and management of Cushing's syndrome; and the relationship between adrenal cortex and hypertension. The description and characteristics of adrenocortical dysfunction are fully covered. The interactions between the adrenal cortex and medulla are extensively discussed. An in-depth analysis of the pharmacokinetics of natural and synthetic glucocorticoids is provided. A study of the regulation of normal steroidogenesis by adrenocortical structure is well presented. A chapter is devoted to possible role of vascular system in neural stimulations. The book can provide useful information to neurologists, doctors, students, and researchers.

Inhalt

Front Cover 1
Adrenal Cortex 3
Copyright Page 4
Table of Contents 9
Preface 5
Contributors 7
Chapter 1. The regulation of adrenocortical function by control of growth and structure 11
Overview 11
THE STRUCTURE OF THE ADRENAL CORTEX 11
REGULATION OF NORMAL STEROIDOGENESIS BYADRENOCORTICAL STRUCTURE 15
Control of the mass of the adrenal cortex 16
The zonation of adrenocortical function 28
SUMMARY: THE CONTROL OF STEROIDOGENESIS BY REGULATION OF ADRENOCORTICAL ZONATION 35
Acknowledgments 36
References 36
Chapter 2. The adrenal cortex in the fetus and neonate 45
INTRODUCTION 45
MORPHOLOGY OF THE FETAL ADRENAL 45
STEROIDOGENESIS BY THE FETAL ADRENAL CORTEX 46
FUNCTIONS OF THE FETAL ADRENAL 58
ADAPTATION TO EXTRAUTERINE LIFE 60
CONCLUSIONS 63
Acknowledgements 63
References 64
Chapter 3 Cellular mechanisms involved in the acute and chronic actions of ACTH 70
INTRODUCTION 70
PROPERTIES OF THE ADRENOCORTICAL STEROID HYDROXYLASES AND RELATED ENZYMES 71
THE ACUTE ACTION OF ACTH 75
THE CHRONIC ACTION OF ACTH 85
COMPARISON OF ACUTE AND CHRONIC ACTIONS OF ACTH 90
Acknowledgements 91
References 91
Chapter 4. On mineralocorticoid and glucocorticoid 99
INTRODUCTION 99
TWO CLASSES OF GLUCOCORTICOID RECEPTORS 101
MINERALOCORTICOID MECHANISMS 102
TYPE I GLUCOCORTICOID RECEPTORS 102
MINERALOCORTICOID?/GLUCOCORTICOID? 103
TYPE I RECEPTORS AND THE GLUCOCORTICOID 'ZEITGEBER9 104
TYPE II RECEPTORS: THE ENDOCRINE EQUIVALENT OF THE SYMPATHETIC NERVOUS SYSTEM 105
SUMMARY 106
References 107
Chapter 5. The adrenarche and adrenal hirsutism 109
THE ADRENARCHE 109
THEADRENOPAUSE 110
THE CONTROL OF ADRENAL ANDROGEN SECRETION 110
ADRENAL HIRSUTISM 116
CONCLUSIONS 125
References 126
Chapter 6 Congenital enzymatic defects of the adrenal 133
INTRODUCTION 133
FETAL SEXUAL DEVELOPMENT 133
ENZYME DEFECTS IN CONGENITAL ADRENAL HYPERPLASIA 134
A PROVOCATIVE CONCEPTUAL APPROACH TO CONGENITALADRENAL HYPERPLASIA: THE FASCICULATA AND GLOMERULOSAAS TWO FUNCTIONALLY DISCRETE GLANDS 139
TREATMENT OF CONGENITAL ADRENAL HYPERPLASIA 146
GENETICS OF CONGENITAL ADRENAL HYPERPLASIA 149
HLA LINKAGE 149
PRENATAL DIAGNOSIS OF CONGENITAL ADRENAL HYPERPLASIA 161
SUMMARY 162
Acknowledgements 162
References 162
Chapter 7 The etiology and management of Cushing's syndrome 167
INTRODUCTION 167
CLINICAL CLASSIFICATION 167
PATHOPHYSIOLOGY OF CUSHING'S SYNDROME 168
TREATMENT OF CUSHING'S SYNDROME 172
FUTURE DIRECTIONS IN CUSHING'S SYNDROME 176
Acknowledgement 178
References 178
Chapter 8 The adrenal cortex and hypertension 182
INTRODUCTION 182
HYPERTENSION AND KNOWN MINERALOCORTICOIDS 182
HYPERTENSION INDUCED BY EXOGENOUS MINERALOCORTICOIDS OR MINERALOCORTICOID-LIKE SUBSTANCES 186
MINERALOCORTICOIDS IN ESSENTIAL HYPERTENSION 188
CONCLUSION 193
Acknowledgement 193
References 193
Chapter 9 Biochemical investigation of adrenocortical dysfunction 201
INTRODUCTION 201
CUSHING'S SYNDROME 202
Acknowledgement 217
References 218
Chapter 10 Interactions between the adrenal cortex and medulla 221
INTRODUCTION 221
ANATOMICAL RELATIONSHIPS BETWEEN ADRENAL CORTEX AND MEDULLA 221
EFFECT OF THE ADRENAL CORTEX ON CATECHOLAMINE SYNTHESIS 223
EFFECTS OF THE ADRENAL MEDULLA ON CORTICAL FUNCTION 226
INTEGRATION OF CORTEX AND MEDULLA IN THE RESPONSE TO STRESS 228
ADRENAL CORTEX AND MEDULLA, RENAL FUNCTION AND ELECTROLYTE HOMEOSTASIS 231
ENDOGENOUS OPIATES AND THE ADRENAL CORTEX AND MEDULLA 236
GLUCOCORTICOIDS AND ADRENAL CATECHOLAMINES: MECHANISMS OF TARGET ORGAN INTERACTIONS 237
CLINICAL IMPLICATIONS OF THE POTENTIATING EFFECT OF CORTICOSTEROIDS ON ADRENERGIC ACTION 239
SUMMARY AND CONCLUSIONS 241
References 242
Chapter 11 Pharmacokinetics of natural and synthetic glucocorticoids 248
PRINCIPLES OF CLINICAL PHARMACOKINETICS 248
PHARMACOKINETICS OF GLUCOCORTICOIDS 254
EFFECTS OF DISEASE ON GLUCOCORTICOID PHARMACOKINETICS 274
EFFECTS OF SIMULTANEOUSLY ADMINISTERED DRUGS ON GLUCOCORTICOID PHARMACOKINETICS 281
EFFECTS OF AGE ON GLUCOCORTICOID PHARMACOKINETICS 284
Index 296

Textauszug

2

The adrenal cortex in the fetus and neonate

Jeremy S.D. Winter

Publisher Summary

Fetal adrenal has the same intrinsic properties and responds to the same pituitary regulatory mechanisms as in postnatal life. The transformation of fetal zone cells occurs within a band of small, dense cells, which are deficient in smooth endoplasmic reticulum. The essential role of the fetal adrenal is to be able to secrete sufficient amounts of cortisol and aldosterone to permit survival immediately after parturition. The major factors that militate against the maintenance of appropriate free cortisol levels in utero include the inhibition of 3β-hydroxysteroid dehydrogenase activity by placental and intra-adrenal steroids and rapid placental and peripheral metabolism of cortisol to cortisone. The characteristic zonal morphology of the fetal cortex reflects a response to the necessarily high levels of plasma adrenocorticotropic hormone (ACTH), as a reduction in ACTH release is consistently followed by rapid adrenal involution. In the normal course of events, this occurs after parturition as the fetal zone becomes transformed to zona fasciculata. Neither the fetal pituitary nor the adrenal cortex possesses unique properties and functions; however, each is forced to perform its usual tasks in a somewhat difficult environment.

INTRODUCTION

During fetal life the human adrenal cortex reaches a size that is, relative to body size, 10–20 times larger than that of the adult. The bulk of this enlargement is contributed by a histologically distinct central fetal zone, which involutes rapidly after birth. These developmental peculiarities, which were recognized by the early years of this century (Elliott and Armour, 1911; Thomas, 1911), have stimulated considerable and sometimes fanciful speculation regarding the physiological role of this gland during fetal life and the factors which regulate its growth and function. In recent years attention has been focused on its massive production of dehydroepiandrosterone (DHA) and other Δ5-3β-hydroxysteroids, and the subsequent metabolism of these steroids by the fetal liver and the placenta. Diczfalusy (1964) developed from such data the concept of a cooperative fetoplacental steroidogenic unit, in which the role of the fetal adrenal was to secrete DHA as an essential substrate for placental oestrogen biosynthesis.

Implicit in this concept is the notion that DHA production must be regulated by some factor of pituitary or placental origin unique to the fetal environment, or that the fetal adrenal cell itself has special steroidogenic properties which disappear spontaneously after birth. This review will present data which indicate instead that the fetal adrenal has much the same intrinsic properties, and responds to the same pituitary regulatory mechanisms, as in postnatal life. These recent observations lead to the alternative hypothesis that the apparent functional and structural peculiarities of the fetal adrenal cortex represent necessary adaptations to metabolic circumstances which derive from the intrauterine environment itself and which disappear at birth.

MORPHOLOGY OF THE FETAL ADRENAL

The primordium of the adrenal cortex appears at about 25 days’ gestation in an area of celomic mesothelium just medial to the urogenital ridge and the developing mesonephros. Initially, the gland is composed of apparently immature cells with poorly developed endoplasmic reticulum, and mitotic activity can be observed throughout. The adrenal enlarges rapidly (Figure 2.1), and by 6–8 weeks’ gestation one can differentiate an inner fetal zone from the outer definitive zone.

Figure 2.1 Adrenal gland weights during human development. (From Neville and O’Hare, 1982, Courtesy of the Publishers, The Human Adrenal Cortex)

Thereafter mitotic activity appears to be restricted to the definitive zone (Crowder, 1957), which is composed of small basophilic cells retaining many of the ultrastructural characteristics of the earlier immature adrenal cells. These cells contribute centripetally via an indistinct transitional zone (Johannisson, 1968) to an enlarging fetal zone, which eventually occupies over four-fifths of the total gland volume. As the adrenal continues to enlarge, mainly due to expansion of the fetal zone, it assumes an extended, flattened form which permits growth without any further increase in total cortical thickness (Dhom, Ross and Widok, 1958).

The large eosinophilic cells of the fetal zone, in contrast to those of the definitive zone, are well differentiated for active steroidogenesis. They show abundant cytoplasm, which is packed with a convoluted network of smooth endoplasmic reticulum, a prominent Golgi apparatus and numerous large mitochondria with a predominantly tubulovesicular internal structure. The development of this fetal zone is clearly ACTH-dependent; it is absent in the anencephalic fetus, but can be restored by administration of ACTH (Johannisson, 1968)

STEROIDOGENESIS BY THE FETAL ADRENAL CORTEX

Substrates

By term, the fetus is producing 100–200 mg of steroid daily, a rate which is several times higher than that of a resting adult (Simmer et al., 1964; Siiteri and MacDonald, 1966). Cholesterol, the obligate precursor for all steroidogenesis, can be synthesized in the fetal adrenal (Bloch and Benirschke, 1959); it is not produced to any degree by the placenta, which uses maternal cholesterol as the substrate for progesterone synthesis. Because in situ perfusion studies suggested that neither circulating acetate nor free cholesterol were efficient precursors for fetal steroidogenesis (Solomon et al., 1967), it has been generally accepted that pre-formed steroids of placental origin had to be provided to the fetal adrenal. Thus, placental pregnenolone was considered to be the natural substrate for DHA, while progesterone was considered to be necessary for any cortisol production by the fetus (Diczfalusy, 1969).

Certainly, fetal tissues can utilize both pregnenolone and progesterone, and there is a significant arteriovenous difference in cord serum levels, indicating some metabolism (Harbert et al., 1964; Hagemenas and Kittinger, 1973); but recent evidence indicates that, just as in the adult, the major substrate for the fetal adrenal is circulating low density lipoprotein (LDL), which is assimilated by a process that first involves binding to specific membrane receptors, and then absorptive endocytosis and hydrolysis to release free cholesterol (Simpson et al., 1979; Carr et al., 1980b). Some cholesterol sulfate may also be derived from this process, and can be metabolized directly to sulfated pregnenolone and DHA (Korte, Hemsell and Mason, 1982).

LDL cholesterol is primarily produced in the fetal liver (Carr and Simpson, 1981b). Cord serum LDL concentrations are considerably lower than those of adults (Winkler, Schlag and Goetze, 1977; McConathy and Lane, 1980), which presumably reflects a high rate of clearance and utilization for steroidogenesis, since levels are much higher in anencephaly (Parker et al., 1980). In addition to this circulating cholesterol, up to 30% of fetal adrenal steroidogenesis may be derived from de novo cholesterol synthesis within the adrenal itself (Carr and Simpson, 1981a). Pituitary ACTH regulates cholesterol availability both by stimulating de novo biosynthesis (Carr, MacDonald and Simpson, 1980) and by increasing the number of LDL receptors (Ohashi, Carr and Simpson, 1981). The fetal zone, as befits its active steroidogenic role, contains more LDL-binding sites per cell and shows a higher rate of de novo cholesterol synthesis than the definitive zone (Carr, Ohashi and Simpson, 1982).

Steroidogenic pathways

The fetal adrenal cortex has the same repertoire of steroidogenic enzymes and uses the same pathways for corticoid and androgen biosynthesis as the adult gland (Yoshida et al., 1978). However, there are striking differences in relative enzyme activity, most notably a marked reduction in 3β-hydroxysteroid dehydrogenase (HSD) activity (Solomon et al., 1967), while the activities of the various cytochrome P-450 associated mixed function oxidases that accomplish the subsequent steps in cortisol synthesis are unimpaired (Shibusawa et al., 1978, 1980). Thus, when pre-formed progesterone is available as a precursor, the major end-products are cortisol, corticosterone and 16-hydroxyprogesterone (Figure 2.2); some aldosterone can also be produced (Dufau and Villee, 1969). However, the major end-product of pregnenolone or cholesterol metabolism is DHA (Figure 2.3). This relative deficiency of 3β-HSD is particularly marked in the inner fetal zone, which also shows a high capacity to sulfurylate the Δ5-3β-hydroxysteroids that are produced (Seron-Ferre et al., 1978; Korte, Hemsell and Mason, 1982). Thus in fresh ACTH-stimulated fetal zone cells the principal steroids produced are DHA sulfate, pregnenolone, pregnenolone sulfate and 17-hydroxypregnenolone, while cortisol is secreted in lesser amounts (Mason, Hemsell and Korte,...

Produkt-Details

• Erscheint lt. Verlag: 22.10.2013
• Sprache: englisch
• Themenwelt: Sachbuch/Ratgeber ► Gesundheit / Leben / Psychologie ► Krankheiten / Heilverfahren
• Themenwelt: Medizin / Pharmazie ► Allgemeines / Lexika
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete
• ISBN-10: 1-4831-9211-3 / 1483192113
• ISBN-13: 978-1-4831-9211-6 / 9781483192116