Adrenocortical cell deletion: The role of ACTH

Apoptosis: A Basic Biological Phenomenon with Wideranging Implications in Tissue Kinetics

“…Fully developed apoptotic bodies show closely packed organelles, which may themselves be condensed (Kerr, 1972b;Wyllie et al, 1972a), but which are apparently intact, both chemically (Kerr, 1965(Kerr, , 1967Ballard and Holt, 1968) and structurally ( Fig. 7 and 11; Klion and Schaffner, 1966;Farbman, 1968;Kerr, 1969Kerr, , 1971Kerr, , 1972a and b; Kerr and Searle, 1972a;Wyllie et al, 1972a;Wyllie et al, 1972b). Lucent cytoplasmic vacuoles and dense masses of nuclear material are seen in some bodies (Fig.…”

“…We have so far studied the evolution of the process with the electron microscope in the normal neonatal rat adrenal (Wyllie et al, 1972a), in embryonic mesenchyme (Crawford, Kerr and Currie, 1972), in both human (Kerr and Searle, 1972a and b) and animal neoplasms, in the adrenal cortex following ACTH withdrawal (Wyllie et al, 1972b), and in various types of liver and adrenal * We are most grateful to Professor James Cormack of the Department of Greek, University of Aberdeen, for suggesting this term. The word " apoptosis " (:T6:cToaIa) is used in Greek to describe the " dropping off " or " falling off " of petals from flowers, or leaves from trees.…”

“…However, examination of the serial changes that take place in several experimental models (Kerr, 1971;Crawford et al, 1972;Wyllie et al, 1972b) suggests that the process is completed fairly rapidly: bodies may form and disappear within 24 hours. Partly degraded remnants of apoptotic bodies are difficult to discern histologically and electron microscopy shows that bodies that can be detected with the light microscope comprise only a small fraction of the total number of cell remnants present (Kerr and Searle, 1972b).…”

“…It is also found in many of the tissues of healthy animals (Kerr, 1965(Kerr, , 1971(Kerr, , 1972aWyllie, Kerr and Currie, 1972a), and its focal appearance at specific times during normal ontogenesis indicates that it is implicated in the fashioning of developing organs and digits, and in the involution of phylogenetic vestiges in the embryo (Glucksmann, 1951;Saunders, 1966;Farbman, 1968;Webster and Gross, 1970). It is prominent in the adrenal gland following withdrawal of adrenocorticotrophic hormone (ACTH) (Wyllie et al, 1972b), and it is involved in other types of atrophy (Kerr, 1971). Thus, although the development of this distinctive type of necrosis, which has previously been called shrinkage necrosis on morphological grounds (Kerr, 1965(Kerr, , 1971, can, in fact, be triggered by noxious agents (Kerr, 1971), it often appears spontaneously or in response to known physiological stimuli, and it is clear that its implications in tissue kinetics are of widely ranging importance.…”

Mechanisms of adrenal gland growth: signal integration by extracellular signal regulated kinases1/2

“…Notably, ACTH induced growth occurred both on the level of cell number and cell size in the rat adrenal gland: exogenous ACTH resulted in a hypertrophic effect of cells from the inner zona fasciculata and medulla but had hyperplastic effects in cells from the outer region of the zona fasciculata indicating also site specific effects of ACTH (Ulrich-Lai et al 2006). On the other hand, reductions in ACTH, by hypophysectomy (Cater & Stack-Dunne 1953) or by continuous activation of the negative feedback loop through glucocorticoid administration, lead to decreased adrenal gland weights, which was thought to be mainly due to an induction of apoptosis ( Wyllie et al 1973, Tchen et al 1977. Although ACTH is a central regulatory element in the hypothalamic-pituitary-adrenal axis, lately other POMC-derived peptides have sparked interest.…”