The Pituitary is not the only producer of TSH. Invasive Bacterial species promote T-cell differentiation, which cause lymphocyte production of an immunoreactive Thyrotropin (irTSH). Low serum thyroxine (T4) levels and increased thyrotropin (TSH) polymorphism suggests an impaired Hypothalamic-Pituitary-Thyroid axis (HPT). Though thyroid atrophy due to chronic under-stimulation could explain the low T3 response to TRH in secondary hypothyroidism known as the Hypothalamic-Pituitary-Thyroid Axis (HPT). It is difficult to reconcile thyroid under-stimulation with normal or increased plasma TSH unless immunoreactive Thyrotropin (irTSH) has low biological activity.
Many patients suffer with hypothyroidism or hormonal symptoms resulting from hypothalamic-pituitary diseases caused by inflammatory processes with impaired blood flow to the Hypothalamus-Pituitary and immune cell activation and production of irTSH.
Immune Cell Regulation of Thyroid Hormones
The low T3 response associated with the hypothyroidism of Hypothalamic-Pituitary-Thyroid Axis (HPT Axis) dysfunction with normal or increased plasma TSH is due to the immunoreactive Thyrotropin (irTSH) having low biological activity. The Pituitary is not the only producer of TSH. Lymphocyte produce an immunoreactive Thyrotropin (irTSH) when exposed to invasive bacteria.
Immune cells (lymphocytes, monocytes and macrophages, granulocytes and mast cells) produce store and secrete numerous hormones.,, Immune cells secrete a thyrotropin (TSH), which is immunologically similar to TSH produced by the pituitary and responds to stimulatory and suppressive feedback in a manner similar to normal TSH but has low or absent biological activity.
The difference in these hormones produced by various stimuli implies that the immune systems may serve a sensory function. Different stimuli (viruses, bacteria, tumors, etc.) would elicit different homeostatic changes in the hormones the immune cells produce. This in turn would alter metabolic functions within the body. The changes in metabolic function would depend on which hormone the Lymphocytes produce.
The end result of this system would be different patterns of physiologic responses that are determined by the particular immune response. Aberrant control of this system might also lead to disease and immune dysregulation. For instance, lymphocyte production of irTSH could be involved in disorders, such as Grave and Hashimoto diseases, which have both immune and thyroid components.,
The immune cells (first of all lymphocytes) have the same machinery which is present in the thyroid gland. This is supported by the fact that thiamazole, an antithyroid drug can influence T3 production by immune cells. Thiamazole (methimazole) inhibits the enzyme thyroperoxidase, which have a key role in T3 synthesis.. This means that thyroperoxidase is also present in the immune cells.
Invasive Bacterial species promote T-cell differentiation, which cause lymphocyte production of an immunoreactive Thyrotropin (irTSH). The thyroid hormone, triiodothyronine (T3) is present in immune cells.,, Not only lymphocytes of the blood, but also the peritoneal fluid and thymus contain this hormone. In addition, T3 is found in other members of the immune system, such as monocytes, macrophages, granulocytes and mast cells.
The cells do not take up T3 (produced by the thyroid gland) from the blood circulation but the hormone –in a bioactive form- is generated by immune cells. These cells have also enzymes for converting thyroxine (T4) to T3.
This means that there is a possibility of regulation of the function of these cells by the thyroid hormones produced by the thyroid gland, by the neighboring immune cells (paracrine regulation) or by autocrine regulation.
Lymphocytes produce immunoreactive thyrotropin (irTSH) when stimulated by bacterial LPS, or stimulated by thyrotropin releasing hormone (TRH). However, TSH regulates T3 concentration in the immune cells and this means, that TSH receptor is also present in (on) the immune cells.
The sensitivity of receptor is very high. A slight increase in TSH is enough for provoking 50% increase of T3 production in immune cells. Direct endocrine action could include a stimulation of thyroid T3 and T4 release followed by the physiologic changes that result from these hormones. Indirect actions on the immune system might then be mediated through these thyroid hormones. For example, leukocytes preferentially take up and deiodinate T3 and T4, and the free iodine is thought to be bacteriocidal for phagocytized organisms. Other indirect activities mediated through T4 are enhanced natural killer cell activity and tumor growth modulation., Thus, stimulation of lymphocyte ir TSH production might result in enhanced antibacterial and antitumor action.
At the same time irTSH can enhance the antibody response. The whole circuit, which is characteristic in the case of the thyroid gland can be found: TRH enhances TSH production of the immune cells, and this latter increases T3 production.
What is the function of the TSH-T3 production and reception in the immune system?
TSH-T3 has an effect on the number and maturation of immune cells. Experiments demonstrated the increasing concentration of growth hormone in the serum –caused by TSH-, which influenced the growth of lymphoid organs and the production of lymphocytes, while other experiments (in an other species) did not justify this.,
TSH is needed for antibody production, and functions as a lymphokine and it regulates the immune response. Thyroid hormone deficiency reduced lymphocyte production and receptor binding capacity, however T4 inhibits T cell cytokine production. T3 regulates dendritic cell maturation and function and helps to express interleukin receptor on peripheral blood mononuclear cells.
Impaired HPT Axis
Hypothalamic activity, neuronal firing and hormone release are dependent on glucose utilization and energy metabolism being delivered by the blood. Hypothalamic ischemia causes decreased mitochondrial function. During chronic ischemia, the hypothalamus and midbrain have more severe neural cell loss than prefrontal cortex, striatum and hippocampus. Of the entire forebrain, the neurons of the hippocampus are the most vulnerable.
The hypothalamus and midbrain are very vulnerable to ischemia. Cerebral ischemia causes hypopituitary function altering the function of the multiple hypothalamic-pituitary axes.
- HPA – Hypothalamic-Pituitary-Adrenal
- HPT – Hypothalamic-Pituitary-Thyroid
- HPG – Hypothalamic-Pituitary-Gonadal
- HPD – Hypothalamic-Pituitary-Digestive
- HPAT – Hypothalamic-Pituitary-Adipose Tissue
- HPR – Hypothalamic-Pituitary-Renal
Hypothyroidism due to insufficient TSH stimulation can be termed central hypothyroidism and can be due 1) to pituitary insufficiency (secondary hypothyroidism) (HPT Axis), 2) to a hypothalamic defect (tertiary hypothyroidism), or 3) to the secretion of biologically TSH with poor responses by immune cells.