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MONOAMINE OXIDASE (MAO) AND THYROID STIMULATING HORMONE (TSH)

I've run across some studies indicating that monoamine oxidase inhibitors (MAOIs) which are used as antidepressant drugs can suppress TSH levels in a fairly high percentage of patients. Monoamine oxidase (MAO) seems depressed in many cases of hyperthyroidism and at an excess in manic depression. I intend to accumulate studies here dealing with these issues in an attempt to figure out what is going on between MAO and TSH.

 

Psychiatry Clin Neurosci 1995 Aug;49(4):231-6

Effects of antidepressants on thyroid stimulating hormone release in rats under ether stress.

Kadono Y, Kaneda H, Maeda K

Department of Psychiatry, Kobe University Medical School, Japan.

We found inhibitory effects of antidepressants (clomipramine, maprotyline, mianserin and zimelidine) and 5-hydroxytryptophan (5-HTP) on thyroid stimulating hormone (TSH) release induced by ether stress in freely moving rats. We confirmed that ether stress suppressed the plasma TSH levels after 30 min. We then injected intravenously 250 ng thyrotropin releasing hormone (TRH), 0.1 mg/kg clomipramine, 2.5 mg/kg maprotyline, 2.5 mg/kg mianserin, 0.5 mg/kg zimelidine and 25 mg/kg 5-HTP simultaneously. These materials blocked the influences on plasma TSH levels by the ether stress. Serotonergic antidepressants (clomipramine, zimelidine) and 5-HTP (precursor of serotonin) had a higher potency against the ether stress. These results suggest that antagonizing effects against the ether stress may involve the serotonergic system in the pituitary gland.

 

Endocrinol 1994 Nov;143(2):303-8

Thyroid iodide transport is reduced by administration of monoamine oxidase A inhibitors to rats.

Cabanillas AM, Masini-Repiso AM, Costamagna ME, Pellizas C, Coleoni AH

Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Argentina.

The present work was addressed to study a possible relationship between monoamine oxidase (MAO) and the thyroid iodide transport mechanism. Normal rats treated with clorgyline (a selective MAO-A inhibitor) or tranylcypromine (a non-selective MAO inhibitor) showed a significantly diminished thyroid MAO activity, while deprenyl and pargyline (MAO-B inhibitors) did not modify the thyroidal enzyme activity with respect to the control group. Under these conditions, in vivo iodide transport was reduced both by clorgyline and tranylcypromine administration whereas it remained unchanged after treatment with MAO-B inhibitors. The effect of MAO inhibitors on thyroid MAO activity and in vivo iodide transport was also evaluated in rats treated with exogenous thyrotrophin (TSH) after endogenous TSH secretion blockade produced by T4 administration. In this condition, thyroid MAO activity was significantly lowered by clorgyline and was not modified by deprenyl. In contrast to the results observed in normal rats, in vivo iodide transport in TSH-treated rats remained unaltered after treatment either with clorgyline or deprenyl. MAO activity evaluated in bovine thyroid follicles in primary culture was highly sensitive to low concentrations of clorgyline (< 10 nmol/l) and relatively insensitive to deprenyl, a finding that indicates a predominance of the MAO-A isoform in the follicular cells in culture. When clorgyline (0.1 and 1 mumol/l) or deprenyl (1 mumol/l) were added to the culture medium, no modifications in the active transport of iodide were observed. These results indicate the absence of a direct linkage between thyroid MAO activity and the active iodide transport.

 

J Endocrinol 1991 Oct;131(1):25-31

Rat thyroid monoamine oxidase (MAO) is regulated by thyrotrophin: evidence that the main form of the enzyme (MAO-A) is not directly involved in iodide organification.

Cabanillas AM, Masini-Repiso AM, Coleoni AH

Catedra de Quimica Clinica I, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Argentina.

The characteristics and regulation of monoamine oxidase (MAO) were studied in rat thyroid tissue. A measured Michaelis constant (Km) value of 102 mumol/l was similar to the Km values found in other tissues. Maximal velocity (Vmax) was 1.028 nmol/mg protein per min. It is known that MAO is present as two isoenzymes, A and B, which are sensitive to clorgyline and deprenyl respectively. The in-vitro effect of graded concentrations of these selective MAO inhibitors was used to estimate the relative proportion of A and B isoenzymes. Clorgyline strongly decreased thyroid MAO activity at concentrations as low as 1 pmol/l while the effect of deprenyl was observed only at concentrations higher than 10 mumol/l. These results indicated that MAO-A is the main form of the enzyme in the rat thyroid. In-vivo administration of L-thyroxine (5.6-224 nmol/kg) significantly reduced thyroid MAO activity at doses equal to or greater than those which have been reported to inhibit iodine output from the thyroid. Increased TSH levels, induced either by exogenous TSH or methimazole administration, resulted in a significant increase in thyroid MAO activity. Theophylline, a phosphodiesterase inhibitor and dibutyryl cyclic AMP were also able to stimulate MAO activity when administered in vivo. Iodide organification (protein-bound 131I) in vivo as well as the relative proportion of the different thyroid iodo-compounds were not affected in animals with reduced or increased thyroid MAO activity induced by clorgyline or theophylline respectively. It was concluded that rat thyroid MAO activity is under the influence of TSH.

 

Br J Pharmacol 1989 Feb;96(2):465-9

Monoamine oxidase activity and triiodothyronine biosynthesis in human cultured thyroid cells.

Kraiem Z, Sadeh O, Youdim MB

Endocrine Research Unit, Carmel Hospital, Haifa, Israel.

1. The proposal that monoamine oxidase (MAO) is a source of peroxide in thyroid hormone biosynthesis has been examined by use of isolated cultured human thyroid cells which retain the ability to secrete triiodothyronine (T3) in response to thyroid stimulating hormone (TSH). 2. The results demonstrated the presence of MAO A and B in human thyroid cells which oxidized 5-hydroxytryptamine and 2-phenylethylamine, respectively, and were selectively inhibited by the MAO inhibitors clorgyline and (-)-deprenyl. 3. Addition of propylthiouracil to the culture system induced a 61% reduction in TSH-stimulated T3 secretion, indicating that the bulk of such secretion apparently derives from de novo iodothyronine synthesis. 4. The MAO A and B substrate, tyramine, was ineffective in stimulating T3 secretion. 5. The selective MAO inhibitors, clorgyline and (-)-deprenyl, alone and in combination, and in the presence and absence of tyramine, failed to inhibit basal as well as TSH-stimulated T3 secretion in cultured human thyrocytes. 6. It is therefore apparent that even though thyroid MAO A and B enzyme reactions result in the generation of H2O2, this H2O2 does not seem to play a significant role in T3 biosynthesis.

 

Horm Metab Res 1983 Apr;15(4):191-3

Effect of hypophysectomy and administration of TSH on the activity of monoamine oxidase in the thyroid gland of rats.

Knopp J, Torda T

The thyroid monoamine oxidase (MAO) activity was measured in rats after hypophysectomy and TSH treatment to find out whether the thyroid MAO activity can be modified with TSH. Hypophysectomy decreased MAO activity in the thyroid gland of rats. The administration of TSH (2.5 U kg-1 daily for 5 days) to hypophysectomized rats increased MAO activity and fully compensated the absence of the pituitary. These data suggest that the thyroid gland MAO activity is under the regulatory influence of TSH.