cholecystokinin and Hypothyroidism

The rat has been a useful model for studying neuronal and metabolic abnormalities associated with fetal and neonatal hypothyroidism produced by treatment of the mother with antithyroid medication. The neonates are then maintained on this medication via the mother's milk until weaning and subsequently through the drinking water. We have determined the concentrations and contents of immunoreactive cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in the brain and gut of groups of rats exposed to antithyroid medication from day 16 of gestation. The neonates were sacrificed at 2, 4, 8 and 12 weeks. Compared to controls total body weight was greatly reduced in methimazole (MMI)-treated rats, all of whom were hypothyroid as evidenced by marked reduction of T4 and increase in TSH. Discontinuation of MMI-treatment after 8 weeks resulted in normalization of T4 and TSH and a dramatic weight gain but at 12 weeks the brain weights of the MMI-treated rats were reduced by 17% and the brain contents, of CCK and VIP were similarly reduced. Tissue weights throughout the gut were 1/2 or less than those of control rats. Since VIP but not CCK concentrations in the gut of MMI-treated animals were significantly greater than those of the control animals, it would appear that there was greater loss of mucosal tissue with its endocrine content of CCK than of neuronal tissue with its greater content of VIP.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Animals; Animals, Newborn; Body Weight; Brain Chemistry; Cholecystokinin; Digestive System; Female; Hypothyroidism; Methimazole; Organ Size; Pregnancy; Radioimmunoassay; Rats; Rats, Inbred Strains; Vasoactive Intestinal Peptide

The influence of long-term changes in thyroid state on insulin secretion was investigated in vivo in mice. Hyperthyroidism was induced by daily injections of L-triiodothyronine and hypothyroidism by a single injection of 131I. Four different insulin secretagogues were used to characterize the insulin secretory response, i.e. glucose, the beta 2-adrenoceptor agonist terbutaline, the cholinergic agonist carbachol and the synthetic C-terminal octapeptide of cholecystokinin, CCK-8. In the hyperthyroid mice the plasma glucose level was moderately decreased. Despite this lower glucose level the insulin response to terbutaline and glucose were potentiated by about 200%. Insulin response to CCK-8 and carbachol was less enhanced, by about 100 and 50%, respectively. Liver and muscle glycogen levels were markedly reduced. The hypothyroid animals showed reduced insulin responses to all secretagogues; after terbutaline by 100%, after carbachol by 70%, after glucose and CCK-8 by 50%. Plasma glucose and muscle glycogen levels were normal, whereas liver glycogen levels were moderately enchanced. Insulin release induced by beta-adrenoceptor stimulation was most markedly affected by the thyroid state, which thus may be of importance for the balance between the beta- and alpha-adrenoceptors of the insulin cell. Since thyroid activity influenced the insulin response to all secretagogues it cannot be excluded that the thyroid state also exerts effects not related to the adrenoceptors.

Topics: Adrenergic beta-Agonists; Animals; Carbachol; Cholecystokinin; Female; Glucose; Hyperthyroidism; Hypothyroidism; Insulin; Insulin Secretion; Mice; Parasympathomimetics; Sincalide; Terbutaline