Inhibitory Action of Oestrogen on Calcium-Induced Mitosis in Rat Bone Marrow and Thymus

Abstract

In the male rat injections of CaCl-2 and MgCl-2 stimulated mitosis in bone marrow and thymus tissue. The magnesium salt was also mitogenic in the normal female, but calcium only exerted its mitogenic effect after ovariectomy. Oestradiol, but not progesterone replacement therpy abolished calcium-induced mitosis in the ovariectomized rat. The inability of calcium to stimulate cell division was also apparent in the thyroparathyroidectomized female rat, suggesting the oestradiol blockage did not operate via some indirect action on the calcium homeostatic hormones calcitonin or parathyroid hormone. When thymic lymphocytes derived from male or female rats were isolated and maintained in suspension, increased calcium or magnesium concentrations in the culture medium stimulated the entry of cells into mitosis. Addition of oestradiol to the culture medium abolished the mitogenic effect of increased calcium levels, but had no effect on magnesium-induced proliferation. These experiments suggested that oestradiol might act at the cell surface to prevent the influx of calcium but not magnesium ions into the interior of the cell and thus to block the sequence of biochemical events which led to the initiation of DNA synthesis and culminate in mitosis.

Optical measurement of membrane potential

“…The effects of extracellular calcium concentrations, as well as steroids, on the membrane potential of lymphocytes was then studied . It had been observed earlier (Smith et al, 1975) that elevation of plasma calcium concentrations stimulates thymic lymphopoiesis in the male, but not in the female rat. However, in vitro, increasing extracellular calcium stimulated proliferation without regard to sex.…”

Inhibition of Magnesium-Induced Mitogenesis by Testosterone

“…The mitogenic action of calcium is not evident in female rats, which can be attributed to the presence of oestrogen (Smith et al 1975). This can be simulated in the culture system by addition of 0-1 µg oestradiol/ml to the cell suspension (Morgan & Perris, 1974).…”

“…This response can be elicited in vivo by injections of calcium or magnesium chloride (Smith, Gurson, Riddell & Perris, 1975). Similarly, in isolated suspension cultures of thymic lymphocytes an increase in the calcium or magnesium concentration also evokes this response (Morgan & Perris, 1974).…”

“…However, since calcium-induced mitogenesis is clearly blocked by the ambient oestrogen levels in the intact female (Smith et al 1975) it is likely that lower physiological concentrations might well be effective in vitro. Nevertheless these properties of the steroids still provide useful tools for selectively discriminating magnesium-dependent mitogenic processes from other proliferative axes.…”