Cell population kinetics was studied by bromodeoxyuridine (BrdU) histochemical and 3H thymidine radioautographic labelling in dog thyroids. In-vivo labelling with BrdU and in-vitro labelling of incubated slices with 3H thymidine gave similar results. This validates the use of in-vitro labelling of slices for the study of cell kinetics in the thyroid. In-vitro labelling of human thyroid slices demonstrated a labelling index of 13.4 x 10(-5) for follicular cells; assuming an S phase of 10 h, this corresponds to a turnover time of the order of 8.5 years for the follicular cells. Stromal cells appear to turn over faster. These results show for the first time that human thyroid cells divide about five times during adulthood and therefore that the steady state level of thyroid cell mass results from a balance between cell division and cell loss. A shorter turnover time was found as expected in the thyroid of an adolescent and in follicular colloid nodules.
The thyroid cell is controlled by a variety of extracellular signal molecules, each interacting through specific receptors with a few intracellular signalling cascades. The main physiological control is exerted in all species by pituitary thyrotropin. Depending on the species, this regulation is complemented or modulated by a variety of hormones, neurotransmitters and local hormones.The main aspects of thyroid cell biology are controlled: the level of its function, the expression of its differentiation and growth and proliferation. In this short review we shall outline our knowledge about the first two aspects but mainly concentrate on the latter, using out own work on the dog thyroid as a framework.Control of the function of the thyrocyte The cyclic AMP system The function of the thyrocyte is mainly regulated by pituitary thyrotropin. The first and probably main target of this hormone is a receptor coupled adenylate cyclase. TSH by binding to its specific receptor at the outer side of the plasma membrane, presumably, as in other cells, activates the GTP binding transducing protein NS, which in turn activates the effector adenylate cyclase at the inner side of the membrane. Such systems have been very good studies for other hormones and neurotransmitters and their specific receptors. In the case of the thyroid, there are few detailed experimental data, and our knowledge on me¬ chanisms is mostly inferred from other model systems. The structure of the TSH receptor is still controversial with estimates about the molecular weight of its subunits varying between 25 000 to 150 000. It was even claimed at one time that this receptor was or included a specific ganglioside. A similar proposal for other tropic hormones and their receptors has been refuted. No detailed study has been carried out on thyroid NS and cyclase.TSH enhances cyclic AMP accumulation in thy¬ roid cells of various species, and this effect has been shown to activate as in other tissues cyclic AMP dependent protein kinases and to cause the phosphorylation of a discrete number of proteins. In the dog thyroid the main fundamental effects of TSH, the activation of thyroid hormone syn¬ thesis, i.e. iodide oxidation, protein iodination and iodotyrosines coupling, as well as the stimula¬ tion of thyroid hormone secretion are reproduced by cyclic AMP analogs and agents increasing cyclic AMP accumulation through non-thyroid specific mechanisms such as forskolin and cholera toxin. They are thus mediated by cyclic AMP. By ana¬ logy with the ß-receptor mediated action of nor¬ adrenalin they have been called ß-effects. For secretion, this conclusion applies to all species
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