Thyrotropin (also called thyrotropin-releasing hormone, TRH, and protirelin) is a naturally occurring hormone produced by the hypothalamus. It stimulates the anterior pituitary gland to release thyroid stimulating hormone (TSH) as well as prolactin. It is used clinically as a treatment for diseases of the spine as well as to treat disturbances of consciousness (e.g. following traumatic brain injury). It is currently being investigated by the United States military as a potential treatment for depression.
Thyrotropin Releasing Hormone Receptors
TRH interacts with cell-surface receptors (called TRH-Rs) to produce its effects much like Sermorelin. There are two TRH-Rs. TRH-R1 is found in the brain, primarily in the hippocampus and on the anterior pituitary. TRH-R2 is found in the hypothalamus, but is only present in rodents and may play a role in feedback1. TRH-R1 is often referred to only as TRHR when discussing human physiology.
The function of TRH-R1 is identical in rodents and humans. That makes it possible to study the effects of TRH binding to the receptor in various regions of the brain. The effects of TRH depend not on the receptor it binds to, but depend upon where the receptor is located, an interesting and somewhat unique physiologic mechanism.
TRH and the Anterior Pituitary
TRH binding to TRHR in the anterior pituitary leads to the release of prolactin as well as the release of TSH. TSH then goes on to bind to receptors on the thyroid gland and cause release of thyroid hormones T3 and T4. Only T3 is active in causing further effects. T4, though inactive, is slowly metabolized to T3. Effects of T3 include
. Increasing cardiac output,
. Increasing heart rate,
. Increasing breathing rate
. Increasing basal metabolic rate,
. Increasing sympathetic activity,
. Improving neuron survival and differentiation, and
. Increasing metabolism of proteins and carbohydrates.
Clinically, synthetic thyroid hormone (called Synthroid) is used directly to treat hypothyroidism and very little else. Elevations in thyroid hormones can lead to increased fat loss and help fight obesity, but side effects have prohibited such use for synthetic thyroid hormone.
Prolactin is often associated with milk production and while that is one of its primary functions, prolactin has more than 300 different actions on the human body. In fact, it is secreted in response to eating, mating, ovulation, and nursing. Some studies have even shown that prolactin plays a major role in animal pair-bond formation in romantic relationships. Other functions of prolactin include-
. Water/salt balance,
. Immune system regulation,
. Cell cycle regulation (it acts as a growth factor),
. Sexual gratification,
. Myelin formation,
. Blood clotting,
. Blood cell formation, and
. Blood vessel development.
TRH and the Hippocampus
The hippocampus is a region of the brain found on the floor of each lateral ventricle in each cerebral hemisphere. Research suggests that it plays active roles in emotion, memory, and the function of the autonomic nervous system. It is one of the first regions in the brain to suffer damage in Alzheimer’s disease.
That TRHRs are found in the hippocampus is unsurprising because TRH has long been known to have anti-depressant and anti-suicidal properties. It has also been shown to have anti-aging properties in mice, which include improved kidney function, improved gonadal function, improved arousal (wakefulness) and improved memory2 .Learn more detailed updates at http://www.medicaldaily.com/thyroid-hormone-thyrotropin-plays-dual-role-metabolism-and-sensing-seasonal-changes-308452
Recently TRHRs have been found in the cerebellum, the part of the brain responsible for balance and coordination. Studies in rats have demonstrated an improvement in ataxic (uncoordinated) gate after administration of both TRH and TRH analogs3 .
TRH is a natural hormone with vast and diverse functions that result from the wide and varied distribution of TRH receptors. Administration of TRH, while stimulating thyroid hormone release, is not associated with the dramatic side effects found with direct thyroid hormone administration. This is because TRH is subject to feedback mechanisms at both the anterior pituitary and (indirectly) at the thyroid gland that attenuate its effects. Its effects in the hippocampus and cerebellum do not appear to be attenuated, however, and thus TRH is under active investigation as a potential treatment for depression, memory problems, and ataxic gate.
- Sun, Y., Lu, X. & Gershengorn, M. C. Thyrotropin-releasing hormone receptors — similarities and differences. J. Mol. Endocrinol.30, 87-97 (2003).
- Pierpaoli, W. Aging-reversing properties of thyrotropin-releasing hormone. Curr. Aging Sci.6, 92-98 (2013).
- Shibusawa, N., Hashimoto, K. & Yamada, M. Thyrotropin-releasing hormone (TRH) in the cerebellum. Cerebellum Lond. Engl.7, 84-95 (2008).