dihydroergotoxine and Hypothyroidism

Monolayer cultures were prepared from the anterior pituitary (AP) lobes of normal male rats and male rats made hypothyroid by treatment with aminotriazole. After 3 days in culture, the cells from hypothyroid animals showed significantly greater TSH and PRL secretory activity and significantly less GH secretory activity than did parallel euthyroid cultures. The responses of euthyroid and hypothyroid cultures to dopaminergic agonists and antagonists were examined. Bromocriptine, apomorphine, and dopamine (DA) inhibited euthyroid TSH secretion by approximately 30%, whereas each drug inhibited hypothyroid TSH secretion by approximately 60% (P less than 0.01 for each drug). In contrast, the three agonists were less effective in inhibiting PRL secretion from hypothyroid cells (P less than 0.05 for each drug). The rank order of potency [bromocriptine greater than (+)butaclamol greater than apomorphine greater than DA greater than (-)butaclamol] shown against secretion was the same for TSH and PRL in both euthyroid and hypothyroid cell cultures and is typical of a DA receptor-mediated process. The binding of [3H]dihydroergocryptine (DHE) to DA receptors on euthyroid and hypothyroid cells was examined under the same conditions in which the secretory responses were determined. One micromolar concentration of (+)butaclamol was used to define nonspecific binding. Specific binding was saturable and stereospecific in each case. The rank order of potency of dopaminergic agonists and antagonists in competing for [3H] DHE binding was the same as that demonstrated against the secretion of TSH and PRL. Each compound displaced significantly more [3H]DHE from hypothyroid cells than from euthyroid cells (P less than 0.05 for each drug). Construction of adsorption isotherms for [3H]DHE binding to DA receptors on euthyroid and hypothyroid cells and subsequent Scatchard analysis revealed a 3- to 4-fold increase in receptor number without a significant change in affinity. Immunohistochemistry on AP lobes before and after dispersion revealed an increase in thyrotrophs and thyroidectomy cells in hypothyroid rats relative to those in control animals. In euthyroid animals thyrotrophs were 10.1% of the total AP cell population, in hypothyroid animals they plus the thyroidectomy cells were 36.3% of the total AP cells. Therefore, the increased number of DA receptors per lobe could be accounted for by increased numbers of thyrotrophs. The mechanism of the altered sensitivity to DA induced

Topics: Animals; Apomorphine; Bromocriptine; Cells, Cultured; Dihydroergotoxine; Dopamine; Hypothyroidism; Male; Pituitary Gland, Anterior; Prolactin; Rats; Rats, Inbred Strains; Receptors, Dopamine; Structure-Activity Relationship; Thyrotropin

Topics: Adipose Tissue; Animals; Cell Membrane; Cricetinae; Cyclic AMP; Dihydroergotoxine; Hyperthyroidism; Hypothyroidism; Kinetics; Male; Mesocricetus; Receptors, Adrenergic; Receptors, Adrenergic, alpha; Thyroid Gland; Thyroxine; Triiodothyronine

The regulation of adrenergic receptors in rat heart was measured in rats made hyperthyroid by injection with thyroxine and made hypothyroid by addition of propylthiouracil to the drinking water. Hyperthyroid rats display cardiac hypertrophy and a decrease in epididymal fat pad weight. The maximal beta-receptor level of ventricular membranes, as determined by (-)-[3H]dihydroalprenolol binding, was increased 60% by thyroxine treatment and decreased about 30% by propylthiouracil treatment. The affinity of the beta receptor was unchanged after thyroxine or propylthiouracil treatment. The maximal activity of the isoproterenol-stimulated adenylate cyclase (EC 4.6.1.1) varied with thyroid state in a manner parallel to the increase in beta-adrenergic binding sites. Thyroxine treatment also increases by 2-fold the beta receptors in isolated rat fat cells. Propylthiouracil treatment lowered the level of alpha receptors in heart by 30% as measured by [3H]dihydroergocryptine binding, but increased the affinity about 2.5-fold. The highest level of alpha receptors was seen in control hearts. These studies indicate that thyroxine may control the turnover of beta-adrenergic receptors in heart and fat cells and regulate physiological responses in these tissues via a hormone-hormone interplay system. Thyroxine treatment reduced the activity of the membrane-bound Mg2+-ATPase (EC 3.6.1.3) and 5'-mononucleotidase (EC 3.1.3.5) but appears to increase the activity of the (Na+ + K+)ATPase (EC 3.6.1.4).

Topics: Adenosine Triphosphatases; Adenylyl Cyclases; Adipose Tissue; Alprenolol; Animals; Cell Membrane; Dihydroergotoxine; Heart; Hyperthyroidism; Hypothyroidism; Male; Propylthiouracil; Rats; Receptors, Adrenergic; Sympathomimetics; Thyroxine