cyclic-gmp and Hypothyroidism

Topics: Chromatography, Ion Exchange; Cyclic AMP; Cyclic GMP; Diabetes Insipidus; Extracellular Space; Glucagon; Humans; Hyperthyroidism; Hypoparathyroidism; Hypothyroidism; Immune Sera; Inosine Nucleotides; Iodine Radioisotopes; Methods; Nucleotides, Cyclic; Phosphorus Radioisotopes; Protein Kinases; Tritium; Vasopressins

Several studies have reported evidence of hormonal abnormalities in 25-35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. In the present study, we examined purinergic relaxation responses in hypothyroidism in an experimental rabbit model and compared them with controls to evaluate the possible involvement of the purinergic pathway.. The study comprised 20 male New Zealand white rabbits. The rabbits were divided into two equal groups. We tested the effects of ATP, alpha beta ATP, and adenosine precontracted with phenylephrine on the isolated corpus cavernosum preparations from control and hypothyroid rabbits. We also evaluated the effects of ATP, alpha beta ATP, and adenosine on the cGMP levels in the isolated corpus cavernosum preparations from control and hypothyroid rabbits.. T3, T4, and testosterone levels were significantly lower in hypothyroid rabbits. ATP, alpha beta ATP, carbachol, and electrical field stimulation (EFS)-induced frequency-dependent relaxation responses in the isolated rabbit corpus cavernosum strips precontracted with phenylephrine reduced significantly (P<0.05). Adenosine-induced relaxation responses did not change significantly in hypothyroid rabbits.. Reduction of relaxation response in hypothyroid rabbits corpus cavernosum can depend on a decreased release of nitric oxide (NO) from nitrergic nerves and endothelium.

Topics: Adenosine; Adenosine Triphosphate; Analysis of Variance; Animals; Cyclic GMP; Disease Models, Animal; Electric Stimulation; Female; Hypothyroidism; Impotence, Vasculogenic; Male; Muscle Relaxation; Muscle, Smooth, Vascular; Penis; Receptors, Purinergic; Testosterone; Thyroid Hormones; Thyroidectomy

The incidence of hormonal dysfunction as a cause of impotence remains controversial. However, several recent studies have reported evidence of hormonal abnormalities in 25-35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. There is some evidence suggesting that hypothyroidism may be a cause of impotence.. We aimed to investigate the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway in hypothyroidism in an experimental rabbit model and compared hypothyroid rabbits with controls to evaluate the possible involvement of the NO/cGMP pathway.. The study comprised 20 male New Zealand white rabbits. The rabbits were divided into two equal groups. The first group had hypothyroidism induced surgically by thyroidectomy for 6 weeks. The second group underwent a sham operation.. There was no significant change in the mean body weight of hypothyroid rabbits and controls. Triiodothyronine and thyroxine levels were significantly lower in hypothyroid rabbits. Plasma thyroid-stimulating hormone and prolactin levels were significantly higher in hypothyroid rabbits. Plasma total calcium and parathormone levels remained in the normal range in both groups.. Papaverine-induced concentration-dependent relaxations were similar in both groups. Carbachol-induced relaxation responses decreased in hypothyroid rabbits. There were significant differences between control and hypothyroid rabbits in frequency-dependent relaxations induced by electrical-field stimulation (EFS). YC-1-induced relaxation responses did not change significantly in hypothyroid rabbits. Concentration-dependent relaxations induced by diethylamine (DEA)/NO were similar in both groups. Amrinone-induced relaxation responses did not change significantly in hypothyroid rabbits.. Reductions of relaxant responses to EFS and carbachol in hypothyroid rabbits can depend on the decrease of released or synthesized NO from nitrergic nerves and endothelium.

Topics: Animals; Carbachol; Cyclic GMP; Disease Models, Animal; Electric Stimulation; Hypothyroidism; Impotence, Vasculogenic; Male; Muscle Relaxation; Muscle, Smooth, Vascular; Nitric Oxide; Nitroprusside; Papaverine; Penis; Rabbits; Thyroidectomy; Vasodilator Agents

Thyroid disease has profound effects on cardiovascular function. Hypo- and hyperthyroidism, for example, are associated with reduced and increased maximal endothelium-dependent vasodilation respectively. We therefore hypothesized that the capacity for vascular nitric oxide (NO) formation is decreased in hypothyroidism and increased in hyperthyroidism. To test this hypothesis, rats were made hypothyroid (HYPO) with propylthiouracil or hyperthyroid (HYPER) with triiodothyronine over 3-4 months. Compared with euthyroid control rats (EUT), HYPO exhibited blunted growth and lower citrate synthase activity in the soleus muscle; HYPER exhibited left ventricular hypertrophy and higher citrate synthase activity in the soleus muscle (P<0.05 for all effects). The capacity for NO formation was determined in aortic extracts by formation of [3H]L-citrulline from [3H]L-arginine, i.e. NO synthase (NOS) activity. Thyroid status modulated NOS activity (EUT, 36.8 +/- 5.5 fmol/h per mg protein; HYPO, 26.0 +/- 7.9; HYPER, 64.6 +/- 12.7; P<0.05, HYPER vs HYPO). Expression of endothelial and neural isoforms of NOS was modulated by thyroid status in a parallel fashion. Capacity for responding to NO was also determined via measuring cGMP concentration in aortae incubated with sodium nitroprusside. Stimulated cGMP formation was also modulated by thyroid status (EUT, 73.0 +/- 20.2 pmol/mg protein; HYPO, 152.4 +/- 48.7; HYPER, 10.4 +/- 2.6; P<0.05, HYPER vs HYPO). These data indicate that thyroid status alters capacities for both formation of and responding to NO. The former finding may contribute to previous findings concerning vascular function in thyroid disease states.

Topics: Animals; Aorta; Citrate (si)-Synthase; Cyclic GMP; Endothelium, Vascular; Hyperthyroidism; Hypothyroidism; Immunohistochemistry; Male; Muscle, Skeletal; Nitric Oxide; Nitric Oxide Synthase; Nitroprusside; Rats; Rats, Sprague-Dawley; Thyroid Diseases; Vasodilator Agents

Hyper- and hypothyroid states occasionally induce skeletal muscle dysfunction i.e. periodic paralysis and thyroid myopathy. The etiology of these diseases remains unclear, but several findings suggest that the catecholamine-beta-receptor-cAMP system or other messenger systems are disturbed in these diseases. In this context, we evaluated changes in the cyclic 3',5'-nucleotide metabolic enzyme, cyclic 3',5'-nucleotide phosphodiesterase (PDE) and calmodulin concentrations in skeletal muscles of hyper- and hypothyroid rats. Activities of cyclic AMP-PDE were low in skeletal muscle both from hyper- and hypothyroid rats, and calmodulin concentration was high in hyperthyroid and low in hypothyroid rats, as compared with normal rats. DE-52 column chromatographic analysis showed that the cGMP hydrolytic activity in peak I and the cAMP hydrolytic activity in peak II were decreased in hypothyroid rats, whereas cAMP hydrolytic activity in peak III was unchanged. The cAMP hydrolytic activity in peak III was decreased in hyperthyroid rats, but the activities in peaks I and II were unchanged. These findings indicate that cAMP and calmodulin may have some role in skeletal muscle function in the hyperthyroid state, and that cAMP and calmodulin-dependent metabolism may be suppressed in the hypothyroid state.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Animals; Calmodulin; Cyclic AMP; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 1; Hydrolysis; Hyperthyroidism; Hypothyroidism; Male; Muscle, Skeletal; Rats; Rats, Wistar; Thyroid Diseases

In order to study the effect of Baji Zibugao (BJZBG, a medicinal plaster mainly consisting of Radix Morindae Officinalis) on the endocrine functions of hypothyroid rabbits, we determined the serum levels of thyroxine (T4), triiodothyronine (T3), cAMP, cGMP and corticosterone in three groups of rabbits: total thyroidectomized and untreated (group I), total thyroidectomized and treated with BJZBG (group II) and controls (group III). The results showed: (1) The serum level of T4 in group I and II after operation was significantly lower than that before operation (P < 0.005), and the serum level of T3 in group I was also lower than that before operation (P < 0.02), but the change of T3 in group II after operation was not significant (P > 0.05); (2) The serum cAMP level in group I after operation decreased and the cGMP level increased (P < 0.025), but the changes of cAMP and cGMP level in group II after operation were not significant (P > 0.05), (3) The change of serum corticosterone level in group I or II after operation was not remarkable (P > 0.05).

Topics: Animals; Cyclic AMP; Cyclic GMP; Drugs, Chinese Herbal; Female; Hypothyroidism; Rabbits; Thyroidectomy; Thyroxine; Triiodothyronine; Yang Deficiency

The regulation of T4 5'-deiodinase activity was studied in cultured GH4C1 cells. Enzyme activity was measured in cell sonicates as the release of radioiodide from [125I]T4. Enzyme activity was stimulated 2- to 3-fold by hypothyroid serum and activators of protein kinase C, such as TRH and phorbol esters. The hypothyroid serum effect was maximal by 3 h, whereas TRH and phorbol esters required 6 h to achieve a maximal effect. The hypothyroid serum effect was gone within 4 h of returning the cells to control medium. In contrast, the TRH and phorbol ester effects persisted 24-48 h after removal of those agents. Both T4 and rT3 were at least as potent as T3 in blocking the effect of hypothyroid serum. The stimulation of 5'-deiodinase induced by hypothyroid serum was additive with that induced by kinase C activators. Trifluoperazine blocked the effect of TRH and phorbol esters, but not that of hypothyroid serum. It is concluded that stimulation of 5'-deiodinase activity can occur by at least two independent mechanisms: one involving hypothyroidism and another involving activation of protein kinase C. The relative potencies of various iodothyronines for abolishing the hypothyroid effect differ markedly from the relative binding affinities of these agents for the nuclear T3 receptor, suggesting that this thyroid hormone effect may not be mediated by the classical nuclear thyroid hormone receptor.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Animals; Calcimycin; Cell Line; Colforsin; Cyclic GMP; Dose-Response Relationship, Drug; Enzyme Activation; Hypothyroidism; Iodide Peroxidase; Phorbol Esters; Pituitary Neoplasms; Protein Kinase C; Rats; Tetradecanoylphorbol Acetate; Thyroid Hormones; Thyrotropin-Releasing Hormone; Thyroxine; Trifluoperazine; Triiodothyronine; Triiodothyronine, Reverse

Adipocyte membranes from hypothyroid rats showed increased low Km cAMP phosphodiesterase activity compared to normals, provided that the subcellular fractionations were done in isotonic, as opposed to hypotonic, buffers. The enhanced cAMP phosphodiesterase activity in hypothyroid membranes was nearly normalized by incubation with a 10-fold excess of cGMP. Preincubation of hypothyroid adipocytes with cGMP also restored to normal the blunted lipolytic response to micromolar concentrations of epinephrine. DEAE-Sephacel chromatography of detergent-solubilized membrane-bound cAMP phosphodiesterase showed a 2.5-fold enhancement in hypothyroid membranes of a form of the enzyme that was completely inhibited by cGMP; the enzymatic elution profiles of the soluble fractions showed no difference between normal and hypothyroid fat pads. The results suggest a possible regulatory role of cGMP in adipocytes in the hypothyroid state.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; 3',5'-Cyclic-GMP Phosphodiesterases; Adipose Tissue; Animals; Bucladesine; Cell Membrane; Cyclic GMP; Cytosol; Dibutyryl Cyclic GMP; Epinephrine; Hypothyroidism; Kinetics; Lipolysis; Male; Rats; Thyroid Gland

Previous observations that cyclic 3',5'-nucleotide phosphodiesterase activity exists in mammalian sera including human serum prompted us to investigate the phosphodiesterase levels in sera of patients with various thyroid disorders. Both serum cyclic AMP phosphodiesterase (cAMP-PDE) and cyclic GMP phosphodiesterase (cGMP-PDE) activities measured in a low substrate concentration were elevated 3-fold in subacute thyroiditis and slightly in hyperthyroidism, compared to the normal. Slight decreases of these enzyme activities were observed in primary hypothyroidism. PDE activities were positively correlated with the value of T3-RSU and serum thyroid hormone levels in hyper- and hypothyroidism. Altered enzyme activities returned to normal during the course of recovery. Identical results were obtained when plasma was tested. These results suggest that serum PDE activities may be partly related to the thyroid function.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; 3',5'-Cyclic-GMP Phosphodiesterases; Cyclic AMP; Cyclic GMP; Humans; Hyperthyroidism; Hypothyroidism; Thyroid Diseases; Thyroid Neoplasms

Topics: Adolescent; Adult; Aged; Cyclic AMP; Cyclic GMP; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged

Plasma levels and 24-h urinary excretion of cyclic AMP and cyclic GMP were measured in 18 patients with hyperthyroidism, 7 patients with hypothyroidism and 25 normal subjects. Mean plasma and urinary levels of both cyclic AMP and cyclic GMP were significantly positive correlations between the serum thyroid hormone levels and plasma and urinary cyclic nucleotide concentrations were also found, suggesting that the elevated extracellular cyclic nucleotide levels in hyperthyroidism are probably a consequence of increased secretion of thyroid hormones. In the hypothyroid patients the extracellular cyclic nucleotide concentrations did not differ significantly from those of the normal subjects.

Topics: Adolescent; Adult; Aged; Cyclic AMP; Cyclic GMP; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyroid Hormones

Topics: Age Factors; Animals; Animals, Newborn; Choline; Cyclic GMP; Female; Guanylate Cyclase; Hypothyroidism; Lung; Phosphoric Diester Hydrolases; Rats; Rats, Inbred Strains; Thymidine; Thyroid Hormones; Triiodothyronine

The effect of insulin-induced hypoglycaemia and methacholine on plasma cAMP and cGMP levels was studied in normal volunteers, hyperthyroid and hypothyroid patients. A significant positive correlation existed between the maximal increase in plasma cAMP and the maximal decrease in plasma glucose in normals during insulin-induced hypoglycaemia. Therefore, the plasma cAMP response is considered to be dependent on the degree of hypoglycaemia, rather than the dose of insulin. The cAMP response to hypoglycaemia was significantly higher in hyperthyroid patient, and was lower in patients with hypothyroidism than in normals. The cAMP response of the hyperthyroid patients was normalized when their hyperthyroidism was controlled after 3 months of treatment. The plasma level of cGMP was slightly elevated during hypoglycaemia, but there was no significant difference between controls and hyperthyroid patients. The cGMP response to methacholine, which is probably mediated by cholinergic receptors, was significantly potentiated in hyperthyroid patients. The cAMP response, which is presumably dependent on endogenous catecholamines secreted during methacholine-induced hypotension, was also enhanced in hyperthyroid patients. It is likely that beta-adrenergic receptor responses and cholinergic receptor responses are both enhanced in hyperthyroidism.

Topics: Adolescent; Adult; Blood Glucose; Catecholamines; Cyclic AMP; Cyclic GMP; Female; Humans; Hyperthyroidism; Hypothyroidism; Insulin; Male; Methacholine Compounds; Middle Aged; Receptors, Adrenergic, beta

Topics: Acetylcholine; Animals; Blood Pressure; Catecholamines; Cyclic AMP; Cyclic GMP; Epinephrine; Humans; Hyperthyroidism; Hypothyroidism; Insulin; Isoproterenol; Physical Exertion; Propranolol; Rats; Stress, Physiological; Tyramine

Evidence is presented that the postnatal rat lung is receptive to several hormones. Experimental diabetes caused a significant depression in lung glucose oxidation rate which was normalized by exogenous insulin therapy. Diabetes also depressed the rate of amino acid incorporation into lung protein; in vitro, insulin stimulated synthesis of selective protein species by the diabetic lung. These results, together with the demonstration of pulmonary receptor sites for insulin and the observation that diabetes selectively affects the ultrastructure of only two cell types in the lung, suggest that insulin may be an important regulator of lung function. That androgens and oestrogens may also exert an effect on the lung is suggested by the presence of distinct receptor activities for these hormones, which appear to be influenced by serum titres of the gonadal steroids. The lung is capable of generating a considerable amount of cyclic GMP in vitro. This ability appears to be dependent upon continued protein synthesis and is influenced by the endocrine state of the animal. Certain steroid hormones are capable of altering cyclic GMP production by the lung when introduced in vitro.

Topics: Adrenalectomy; Animals; Cyclic GMP; Cytosol; Diabetes Mellitus, Experimental; Hormones; Hypothyroidism; Insulin; Lung; Organ Specificity; Rats; Receptors, Androgen; Receptors, Estrogen

Topics: Animals; Cats; Cyclic AMP; Cyclic GMP; Electric Stimulation; Female; Guinea Pigs; Heart; Hypothyroidism; In Vitro Techniques; Male; Myocardial Contraction; Myocardium; Papillary Muscles; Phenoxybenzamine; Propylthiouracil; Rats; Receptors, Adrenergic; Receptors, Adrenergic, alpha; Time Factors

Topics: Animals; Body Weight; Brain; Cyclic AMP; Cyclic GMP; Hypothyroidism; Liver; Male; Muscles; Rats; Thyroxine; Time Factors

Urinary cyclic AMP, cyclic GMP and creatinine excretion were measured in 38 patients with hyperthyroidism, 32 patients with hypothyroidism and in 57 normal subjects. The excretion of both cyclic nucleotides was significantly increased in hyperthyroid females, but not in hyperthyroid males. The cyclic nucleotides/creatinine ratios, however, were uniformly elevated in both male and female hyperthyroid subjects and this was due, in part, to decreased creatinine excretion. Cyclic AMP excretion was significantly decreased in the hypothyroid subjects, but the cyclic AMP/creatinine ratios were not significantly different from normal. There were no significant alterations in cyclic GMP and cyclic GMP/creatinine ratios in the male hypothyroid patients, but ratios in the female patients were slightly greater than in the normals. These results demonstrate that hyper- and hypothyroidism may be associated with appreciable alterations in urinary cyclic nucleotide levels and that there may be sex-related differences in the patterns of urinary excretion of these nucleotides. The cyclic nucleotide levels herein described in patients with hyper- and hypothyroidism are qualitatively and, in some instances, quantitatively similar to those found in patients with hyper- and hypoparathyroidism, respectively.

Topics: Creatinine; Cyclic AMP; Cyclic GMP; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Sex Factors

Evidence is presented that modulation of the maximum velocity of a particulate low K-m cyclic adenosine 3':5'-monophosphate (cyclic AMP) phosphodiesterase by thyroid hormones is one mechanism for the regulation of the responsiveness of rat epididymal adipocytes to lipolytic agents such as epinephrine and glucagon. Fat cells of propylthiouracil-induced hypothyroid rats are unresponsive to lipolytic agents and the V-max of particulate low K-m cyclic AMP phosphodiesterase of these cells is elevated above normal. In vivo treatment of hypothyroid rats with triiodothyronine restores to control values both the lipolytic response of the fat cells to epinephrine and the V-max of the particulate bound low K-m cyclic AMP phosphodiesterase. No similar correlation is found with the soluble high K-m cyclic AMP phosphodiesterase. The phosphodiesterases of fat cells from normal and hypothyroid rats respond identically in vitro to propylthiouracil, triiodothyronine, methylisobutylxanthine, or theophylline, although the particulate low K-m cyclic AMP phosphodiesterase is inhibited to a greater extent than soluble cyclic guanosine 3':5'-monophosphate phosphodiesterase activity. Protein kinase of fat cells from hypothyroid rats can be stimulated by cyclic AMP to the same total activity as observed in fat cells of normal rats. However, less of the protein kinase in fat cells from hypothyroid rats was in the cyclic AMP-independent form. This shift in the equilibrium of protein kinase forms is consistent with an increased activity of low K-m cyclic AMP phosphodiesterase and probably results from a lowering of the lipolytically significant pool of cyclic AMP.

Topics: Adipose Tissue; Animals; Bucladesine; Cyclic AMP; Cyclic GMP; Epinephrine; Glycerol; Hypothyroidism; Kinetics; Lipid Mobilization; Male; Phosphoric Diester Hydrolases; Propylthiouracil; Protein Kinases; Rats; Theophylline; Thyroid Gland; Thyroid Hormones; Time Factors; Triiodothyronine; Xanthines