Dr. Ron’s Research Review – March 14, 2012

This week’s research review focuses on thyrotropin-releasing hormone (TRH).

Thyrotropin-releasing hormone (TRH), also called thyrotropin-releasing factor (TRF), thyroliberin or protirelin, is a tropic, tripeptidal hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary.

A recent study examined the effects of long-term intraperitoneal injection of thyrotropin-releasing hormone (TRH) on aging- and obesity-related changes in body weight, lipid metabolism, and thyroid functions on anterior hypothalamus-lesioned obese mice and genetically obese mice. The treatment provoked a mobilization of triglycerides in the peripheral blood, a decrease of leptin and a loss of body weight. The weight loss did not depend on TSH-mediated stimulation of thyroid hormone secretion with consequent metabolic hyperthyroidism. The levels of blood cholesterol were not affected or even suppressed. Even at a very high dosage TRH did not affect the obesity of genetically obese mice. (Pierpaoli and Lesnikov 2011)

Walter Pierpaoli published a report on the experimental evidence that, while melatonin alone exerts a low-level age-postponing activity, its age-delaying effects are greatly enhanced and accelerated when given in combination with a pineal peptide, thyrotropin-releasing hormone (TRH). (Pierpaoli, Bulian et al. 1999)

An increase of serum GH concentration followed TRH injection in patients with primary hypothyroidism. (Hamada, Uoi et al. 1976)

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Articles

Increase of serum GH concentration following TRH injection in patients with primary hypothyroidism

            (Hamada, Uoi et al. 1976) Download

The effect of TRH administration on serum GH was studied in 6 normal subjects, 13 patients with primary hypothroidism and 6 thyrotoxic subjects. Although no appreciable changes of serum GH were noted in the normal subjects, TRH administration provoked an increase of serum GH in 6 out of 13 patients with primary hypothyroidism. Serum GH levels in response to TRH administration were decreased in patients who were euthyroid following treatment with a preparation of desiccated thyroid. In patients with hyperthroidism, no significant response of serum GH was observed at 30 or 60 min after TRH administration. Some of the patients with hyperthyroidism showed a slight increase in serum GH at 120 min after TRH injection. These results suggest that hypothalamo-pituitary function regulating GH secretion is altered in patients with primary hypothyroidism.

Effects of long-term intraperitoneal injection of thyrotropin-releasing hormone (TRH) on aging- and obesity-related changes in body weight, lipid metabolism, and thyroid functions

            (Pierpaoli and Lesnikov 2011) Download

Adult adipose mice, high fat diet-fed (HFD) mice, anterior hypothalamus-lesioned obese mice and genetically obese mice, were injected daily with thyrotropin releasing hormone (TRH). The treatment provoked a mobilization of triglycerides in the peripheral blood, a decrease of leptin and a loss of body weight. The weight loss did not depend on TSH-mediated stimulation of thyroid hormone secretion with consequent metabolic hyperthyroidism. The levels of blood cholesterol were not affected or even suppressed. Even at a very high dosage TRH did not affect the obesity of genetically obese mice. The ubiquitous tripeptide TRH may thus constitute a key element in the hormone-controlled regulation of body weight and fat stores in the adult and aging body.


Thyrotrophin Releasing Hormone Accelerates and Enhances the Age-Postponing Effects of Melatonin

         (Pierpaoli, Bulian et al. 1999) Download

Studies over a period of several years have suggested an age-postponing effect of circadian nocturnal administration of melatonin and of young-to-old pineal grafting in rodents. Of the two procedures, the effect of pineal grafting was significantly more pronounced. Also, old-to-young and young-to-old pineal transplantation in normal or pinealectomized recipients suggested that the pineal itself contains the capacity to prevent or to accelerate the course of aging depending on the age of the donor and/or of a recipient when the pineal is transplanted. This observation prompted the idea that the "program of aging" might be governed by the capacity of the pineal to maintain the control of central neuroendocrine functions and to constantly synchronize the synthesis and release of hormones according to a strict circadian periodicity and seasonal rhythmicity. This report deals with the experimental evidence that, while melatonin alone exerts a low-level age-postponing activity, its age-delaying effects are greatly enhanced and accelerated when given in combination with a pineal peptide, thyrotropin-releasing hormone (TRH). This peptide may be a key element in the mechanism by which both melatonin and pineal grafting might postpone aging. In fact, as suggested by our data here, TRH could be one of the basic mediators in the brain (pineal-hypothalamic-hypophyseal axis) and in peripheral endocrine glands (e.g., the β, insulin-producing cells in the pancreas). TRH may directly translate the light and temperature-mediated environmental stimuli into rapid energy-adapting biochemical processes which constantly monitor cell functions relating to energy production, in particular those required for thermoregulation. We show here that this energy-monitoring action of TRH is not thyroid mediated. We also show that TRH is not itself a toxic agent even when administered daily for long periods at a very high pharmacological dosage.


References

Hamada, N., K. Uoi, et al. (1976). "Increase of serum GH concentration following TRH injection in patients with primary hypothyroidism." Endocrinol Jpn 23(1): 5-10.

Pierpaoli, W., D. Bulian, et al. (1999). "Thyrotrophin Releasing Hormone Accelerates and Enhances the Age-Postponing Effects of Melatonin." Journal of Anti-Aging Medicine 2(4): 343-348.

Pierpaoli, W. and V. A. Lesnikov (2011). "Effects of long-term intraperitoneal injection of thyrotropin-releasing hormone (TRH) on aging- and obesity-related changes in body weight, lipid metabolism, and thyroid functions." Curr Aging Sci 4(1): 25-32.