The Role of Hormones and Ions in the Physiological Control of Cellular Proliferation in Rat Erythropoietic and Lymphopoietic Tissues

Abstract

Physiological situations are described in which changes in the mitotic activities of rat bone marrow and thymus are precisely regulated by modulations of the calcium homeostatic system. In this context, other hormones are demonstrated to interact with those controlling calcium homeostasis. Erythropoietin and the antidiuretic hormone have been studied in depth and are shown to be co-ordinated with the parathyroid gland in the genesis and maintenance of the enhanced bone marrow mitosis which is necessary to restore lost red cell mass. Observations in vitro have led to hypotheses to explain the mechanisms of action of these hormones. Circadian variations in bone marrow and thymus mitotic activity are shown to closely parallel shifts in plasma calcium concentration. These calcium changes are probably dependent upon fluctuations in the activity of the parathyroid gland. The mitogenic properties of exogenous erythropoietin are largely mediated via elevations in calcium in the plasma. The bone marrow response to haemorrhage is dependent upon the co-ordinated actions of parathyroid hormone and calcium, erythropoietin and anti-diuretic hormone. Interrelationships between other erythropoietic stimulants or inhibitors and calcium homeostasis have been briefly investigated in the whole animal. Studies using in vitro bone marrow cultures suggest a role for cyclic adenosine 3’, 5’ — monophosphate in the intracellular mediation of mitogenic stimulants. Proliferative activity in the thymus following erythropoietic stimuli has a number of parallels with that in bone marrow. The functional Significance of this observation is not clear. Thus the hormones of the calcium homeostatic system, via their ability to modulate body mobile calcium, constitute an important control factor in the physiological regulation of cell proliferation in bone marrow and thymus.