ContributorsPrefaceChapter 1. The Structure of the Mammalian Adrenal Cortex 1. Introduction 2. Methodology 3. General Structure of the Normal Adult, Eutheria 4. Metatheria 5. General Features of Cell Organelles 6. Cytochemistry and Autoradiography at the Ultrastructural Level 7. The Embryonic Mammalian Adrenal Cortex: Morphology and Cytochemistry 8. The Fetal or Transient Cortex and the X Zone 9. Cytophysiology of the Mammalian Adrenal Cortex 10. Stimulation in Experimental Hypoadrenocorticism 11. Problems Associated with the Structure of the Mammalian Adrenal Cortex 12. Conclusion Acknowledgments ReferencesChapter 2. Steroidogenesis in the Zones of the Mammalian Adrenal Cortex 1. Introduction 2. Glucocorticoids 3. Mineralocorticoids: Acute Factors Affecting Secretion 4. Mineralocorticoids: Chronic Factors Affecting Secretion 5. The Renin-Angiotensin System 6. Functional Aspects of Adrenocortical Zonation 7. Inner Zone Function 8. Metatheria 9. Adrenocortical Sex Steroids and Gonadotrophins ReferencesChapter 3. Catabolism of the Adrenocortical Hormones 1. Introduction 2. Catabolic Transformations 3. Catabolism of Specific Hormones ReferencesChapter 4. The Adrenal Gland in Reptilia Part 1. Structure 1. Introduction 2. General Morphology 3. Histology 4. Ultrastructure 5. Seasonal Changes 6. The Pituitary-Adrenal Axis 7. The Hypothalamo-Hypophysial Axis References Part 2. Physiology 1. Adrenocortical Control Mechanisms 2. Corticomedullary Relationships 3. Water and Electrolyte Balance 4. Protein, Fat and Carbohydrate Metabolism ReferencesChapter 5. The Adrenal Cortex of Amphibia 1. Structure of the Adrenal Islets 2. Functions of Adrenocortical Secretions Acknowledgments ReferencesChapter 6. The Actions of Aldosterone 1. Introduction 2. Effects and Actions of Aldosterone 3. Mechanism of Action of Aldosterone 4. Conclusion ReferencesChapter 7. Aldosterone Secretion and its Clinical Disorders Part 1. Control of Aldosterone Secretion 1. Controlling Factors 2. Physiological Variations in Aldosterone Secretion Part 2. Disorders of Aldosterone Secretion 1. Primary Aldosteronism 2. Syndromes Resembling Primary Aldosteronism 3. Hypertension and Aldosteronism 4. Secondary Aldosteronism 5. Hypoaldosteronism References
8 The fetal or transient cortex and the X zone
Starkel and Wegrznowski (1910) first described a special region of the human adrenal cortex, the fetal or transient cortex. Reviews are available in Lanman (1953, 1957). Sucheston and Cannon (1968) gave the following characteristics of the fetal cortex: (a) large, polyhedral cells; (b) located between the maturing (permanent) cortex and the medulla; (c) its disappearance as an entity as the permanent cortical material gives rise to the post-natal and adult pattern. The involution means that adrenal weight falls considerably immediately after birth. The fetal cortex is seen not only in man, monkey and armadillo, but also in the sloth (Hartman, 1959), the cat (Davies, 1937), the leopard, tiger, lion and elephant seal (Deanesly, 1961) and the pig (Katsnel’son et al., 1963). Those species in which the inner part of the developing adrenal cortex does not show degenerative changes at birth or shortly thereafter are not regarded as possessing a transient cortex, two examples being the guinea pig and the rat. However, Nussdorfer (1970a,b) suggests that in the newborn rat adrenal cortex, dark cells of the zona juxta-medullaris are degenerating cells which might therefore be considered as a transient cortex.
In seeking the genesis of the transient cortex, chorionic gonadotrophin (hCG in man) has been implicated (Rotter, 1949a,b; Chester Jones, 1955, 1957; Lanman, 1957). The perfusion of the previable fetuses with an anti-hCG seemed to decrease the presumptive secretory activity (Johannisson, 1968). The problem is unresolved and probably, too, the transient cortex may depend on secretions of the anterior lobe of the pituitary. This is indicated by the human anencephalic embryo in which the brain is much reduced and the pituitary poorly developed or absent. Here the permanent cortex is normal and the transient cortex little developed or absent (Tähkä, 1951; discussion in Chester Jones, 1957). Satow et al. (1972) found only a few ACTH-like cells in the anterior pituitaries of anencephalics so ACTH cannot be ruled out as a controlling factor in the zone’s normal expression. Further, Lanman (1962) showed that the administration of ACTH to post-natal anencephalics resulted in the appearance of cells in the comparable area to the transient zone. In general, the ultrastructure shows no criteria associated with steroidogenesis though administration of ACTH gives changes compatible with this capacity (Johannisson, 1968). Thus, ACTH cannot be ruled out as a controlling factor of the embryonic adrenal cortex at one stage or another.
The X zone of the mouse adrenal cortex has intrigued many workers over the years and it has been made the more enigmatic by the interesting and extensive studies of Delost and his co-workers on this and other species (Delost, 1955, 1956; Delost et al., 1972; Delost and Delost, 1954; Chirvan-Nia, 1967). The early history of the mouse adrenal has been fully documented by Chester Jones (1957), and Shire (1970) covers later aspects. Briefly the mouse adrenal cortex possesses a juxta-medullary zone comprising cells with acidophilic cytoplasm and prominent basophilic nuclei, varying in expression according to age and sex. The zone is generally referred to as the X zone (Howard-Miller, 1927) but it has other names (“boundary zone” Waring, 1935; “interlocking zone” Roaf, 1935; “androgenic zone” Grollman, 1936; “sexual zone” Cano Monasterio, 1946; Botella Llusia and Cano Monasterio, 1950). The name “transient zone” (Whitehead, 1933) has come back into favour to describe the X zone of some mammals and the fetal cortex as a blanket term until such time as functions are ascribed thereto (Sucheston and Cannon, 1968). The blood system of the mouse adrenal cortex with a hypertrophied X zone has been displayed by Gersh and Grollman (1941; Fig. 44). The fine structure of the X zone has been described in the young female mouse by Ross (1967), Sato (1967) and Hirokawa and Ishikawa (1974). In contrast to the cells of the zona fasciculata (and the human transient zone), those of the X zone are smaller. Large numbers of variously shaped mitochondria are observed throughout the cytoplasm. They are round, oval, elongated, club-shaped, ringshaped or dumbbell-like and range from 0.4 to 2.6 μm in diameter. Most have lamelliform cristae.
Fig. 44 The vascular pattern of a hypertrophied mouse adrenal gland containing an X zone. The mouse was given powdered thyroid extract mixed with the diet at two weeks of age and kept on it for two further weeks. The resultant marked adrenocortical hypertrophy was most striking in the X zone. Anastomoses between the capillaries in the periadrenal fat and those in the capsule were more numerous than in normal animals. In addition, several capillaries extending between the kidney and the adrenal capsule were visible. The blood vessels in the capsule and the zona glomerulosa conform in other respects to the normal pattern. In the zona fasciculata the capillaries were more definitely orientated longitudinally and more numerous than normal. As the capillaries approach the X zone, they increase in diameter and become progressively wider as they converge to join the first-order collecting vein in the medulla. The function of the X zone is unknown and this type of preparation has not been investigated with recent methods for the determination of hormones. (From Gersh and Grollman, 1941.)
Although the X zone cells may, perhaps, be identified earlier (Waring, 1935), they form a clearly recognizable juxta-medullary area at about 14 days of age in the mouse. The zone then quickly increases in size as does the rest of the cortex. In the male, the X zone collapses by the direct action of androgens produced at maturity (Deanesly and Parkes, 1937; Chester Jones, 1949b). This collapse is achieved by pycnosis of the nuclei and shrinkage of cell cytoplasm, the whole settling down on the medulla and the connective tissue trabeculae forming a perimedullary capsule. Thus the young adult mouse has no X zone but a connective tissue capsule surrounding the medulla. Castration before puberty removes endogenous testicular androgens and the enhanced gonadotrophin secretion allows the X zone to continue development under the influence of the LH fraction which is trophic to the X zone and which is not controlled by ACTH (Chester Jones, 1949a). Post-pubertal castration of the adult mouse shows the capacity of the gonadotrophin to act upon the inner cells of the zona fasciculata to give a wide secondary X zone (Chester Jones, 1949a, 1955).
In unmated females, the X zone does not disappear at puberty. The extent of the X zone, up to 50% in some strains, and the time after puberty at which it may degenerate in the unmated female depends on the strain (Chester Jones, 1957; see Shire, 1970 for literature and discussion). The collapse of the zone is generally by “fatty degeneration”. The postnatal development of the X zone has been analysed by Müntener and Theiler (1974) and Hirokawa and Ishikawa (1974). At 0–5 days of age, all inner cortical cells contain mitochondria with vesiculo-tubular cristae and electron-lucent liposomes. The first sign of the developing X zone is the appearance of small groups of special cells in the juxta-medullary region at 8 days. They contain nuclei of irregular outline and some parallel stacks of flattened SER to form a thin but clearly identified layer at 10–11 days. The typical X zone cells are characterized by the formation of peculiar mitochondrial complexes (Ross, 1967; Sato, 1967, 1968) and the possible mechanism of formation is given in Fig. 45. Tubular or vesicular SER tend to be packed and take a flattened cisternal form and these parallel stacks often organize into a whorled pattern. The typical, uninvoluted X zone has very few lipid droplets. In this condition it might be expected to produce steroids though this has not been shown. The transformation of mitochondrial cristae from vesicular or vesiculo-tubular to lamellar does not support steroidogenic activity though the whorled pattern of the SER might do so (see Christensen, 1965; Bjersing, 1967; Ross, 1967).
Fig. 45 A possible mechanism for the formation of the peculiar mitochondrial complex in the X zone of the mouse adrenal cortex. The complex shows a regular repeating pattern of an ER cisterna, outer and inner mitochondrial membranes, a longitudinal crista, inner and outer mitochondrial membranes in that order. The arrows indicate the direction of the process. (From Hirokawa and Ishikawa, 1974.)
The X zone of the mouse in most strains disappears during days 7 to 12 of the first pregnancy; thus multigravidae do not have an X zone. The results of Chester Jones (1952) gave support to the idea that ovarian androgens were the prime cause of this rapid disappearance. It should, however, be pointed out that the problems of the trophic hormone for the X zone and its responses to steroids remain unresolved. Whilst it has become a...
