The possible mediation by cyclic AMP of parathyroid hormone‐induced stimulation of mitotic activity and deoxyribonucleic acid synthesis in rat thymic lymphocytes

Abstract

Purified parathyroid hormone (PTH) strongly stimulates the initiation of deoxyribonucleic acid (DNA) synthesis and thereby raises the flow of cells into mitosis in rat thymic lymphocyte populations maintained i n vitro. These actions of PTH are potentiated by caffeine and inhibited by imidazole which indicates that the hormonal action is mediated by cyclic adenosine 3',5',-monophosphate (cyclic AMP). The feasibility of cyclic AMP being the mediator of PTH action is established by the observation that a low concentration ( 1 0 -7 M ) of dibutyryl cyclic AMP precisely mimics the stimulatory action of the hormone on DNA synthesis and cell proliferation.

Thymus-derived lymphocytes and their interactions with macrophages are required for the production of osteoclast-activating factor in the mouse.

“…Furthermore, at least one instance in which T cells or a thymic factor (or both) control bone resorption in vivo has been reported in the literature (34,35): osteopetrotic (op/op) rats, in which osteoclasts are present but not active, have been shown to resume normal osteoclastic bone resorption when injected with normal thymic cell suspensions, therefore also raising the possibility of a role for the T lymphocytes in osteoclast activation, both in vivo and in vitro. Finally, T lymphocytes have been shown to have receptors for PTH (36,37), calcitonin (38), and 1,25-(OH)2-vitamin D3 (39), the three major calcium-regulating hormones with specific effects on bone cells and bone remodeling; vitamin D metabolites have also been shown to have marked effects on the differentiation of cells of the Proc. NatL Acad Sci.…”

Parathyroid Hormone and the Cellular Immune System

“…Inhibition o f E rosette formation by P T H was also reported by Giacchino et al However, other investigators claimed that PT H has a stimulatory effect on T lymphocytes. PTH-induced stim ulation of mitotic activity and deoxyribonucleic acid syn thesis in rat T cells was reported in 1977 by Whitefield et al [25] who assumed that this action is mediated via cA M P . Perry [26] found that the amino-terminal frag ment activates mononuclear leukocytes, causing them to produce a substance that enhances bone resorption.…”

Cyclic 3′-5′-adenosine Monophosphate: Its Possible Role in Mammalian Cell Mitosis and Radiation-induced Mitotic G2-delay

“…Various hormones, and elevated concentrations of calium and magnesium, have been shown to exert a mitogenic action on thymus lymphocytes Youdale 1969, Whitfield, Perris and. The hormone action is dependent on the availability of calcium, but can be mimicked by c-AMP (Whitfield, MacManus and Rixon 1970) and apparently is due to a stimulation of the entry of cells into the DNA-synthetic S-phase of the cycle. Radiation-induced mitotic delay in these cells has also been found to be diminished by the same agents and mechanism of action (Whitfield, Rixon and Youdale 1969).…”