Virginia H. Black

Accumulation of very long chain fatty acids in X-linked and neonatal forms of adrenoleukodystrophy (ALD) appears to be a consequence of deficient peroxisomal oxidation of very long chain fatty acids. Peroxisomes were readily identified in liver biopsies taken from a patient having the X-linked disorder. However, in liver biopsies from a patient having neonatal-onset ALD, hepatocellular peroxisomes were greatly reduced in size and number, and sedimentable catalase was markedly diminished. The presence of increased concentrations of serum pipecolic acid and the bile acid intermediate, trihydroxycoprostanic acid, in the neonatal ALD patient are associated with a generalized diminution of peroxisomal activities that was not observed in the patient with X-linked ALD.

Abstract Smooth endoplasmic reticulum appears in interstitial cells and Sertoli cells of 22–24d testes of fetal guinea pigs before the beginning of morphological differentiation of the male reproductive tract at 29d (Price et al., '67), and before the appearance of demonstrable 3β‐hydroxysteroid dehydrogenase, an enzyme important in steroid biosynthesis, in the interstitial cells at 29d (Ortiz et al., '66). This enzyme has not yet been demonstrated in the Sertoli cells. The smooth reticulum of the interstitial cells increases in amount, filling the cells with tubules by 27d, and later forming some fenestrated cisternae which are occasionally seen in whorls. In Sertoli cells, the tubular reticulum shows signs of degeneration at 26d. After this time the cisternal endoplasmic reticulum in these cells increases in amount and by 45d is predominantly smooth‐surfaced. Yet it is never as prominent as the smooth reticulum of the interstitial cells. Scattered clusters of ribosomes or polyribosomes are seen on the surface of the tubular reticulum of these differentiating cells. These polyribosomes become more widely spaced as the smooth‐surfaced areas increase and may be associated with the production of smooth membranes. Smooth endoplasmic reticulum is known to play a role in the production of steroid hormones, and therefore the extensive development of smooth reticulum in fetal interstitial cells is consistent with experimental evidence that implicates these cells as the chief source of steroid hormones governing male reproductive tract differentiation.

Abundant membrane-bounded granules, 0.1-0.45 microm in diameter, occur among the elements of the smooth-surfaced endoplasmic reticulum in zona fasciculata and zona reticularis adrenocortical cells of guinea pigs. Acid phosphatase cannot be cytochemically demonstrated in them, and they are therefore distinct from lysosomes. Incubation in medium containing 3,3'-diaminobenzidine results in dense staining of the granules, identifying them as peroxisomes. These small peroxisomes increase in number as fetal adrenocortical cells differentiate, and they appear to arise from dilated regions of endoplasmic reticulum. They maintain interconnections with the smooth endoplasmic reticulum and with one another.

Comparison of the fine structural features of guinea pig adrenocortical cells as seen in thin sections with those revealed by freeze-fracture confirms the structural appearance of steroid-secreting cells as interpreted from thin sections and reveals significant new features of the membranous organelles. Smooth-surfaced endoplasmic reticulum appears as a network of tubules, interwoven or in parallel, and as cisternae, fenestrated and non-fenestrated. These elements are tightly packed in the deeper cortical cells, excluding other organelles from their domain. Tubules and fenestrated cisternae possess randomly distributed intramembranous particles on their PF faces, while closely packed non-fenestrated cisternae possess aggregates of particles interspersed with aparticulate regions on their PF faces. These differences in particle distribution suggest functional specialization among the various forms of reticulum. Mitochondria appear as elongated structures of varying shape. Freeze-fracture reveals that all their cristae have circular origins from the inner membrane. Sinuous tubules, which appear as tubules in section, and straight tubules, which appear as lamellae in section, arise from single sites. Flattened sac-like cristae may have multiple circular origins. Definite contact points seen between inner and outer membranes may facilitate passage of molecules, including steroids, into the mitochondrial compartments. Lysosomes and peroxisomes, which are easily identified in thin sections with the aid of cytochemistry, are difficult to identify with certainty by freeze-fracture. Single membrane-bound granules of slightly smaller diameter than mitochondria may represent lysosomes. Smaller granules interconnected with the tubular reticulum, as well as dilated regions of this organelle, may represent peroxisomes. Plasma membranes show no indication of tight junctions but do have abundant gap junctions which show a zonal differentiation: small gap junctions throughout the cortex, medium-sized regularly shaped gap junctions in zona fasciculata externa, and large irregular gap junctions in zona fasciculata interna and zona reticularis. The large junctions cover planar areas as well as surfaces of projections of one cell into another. Such junctions may allow passage of ions as well as of low-molecular-weight substances between the cells, facilitating or even amplifying the response to trophic hormone stimulation.