The ultrashort feedback mechanism is a regulatory circuit of endocrine secretion in autocrine and paracrine glands. In this feedback loop, a hormone inhibits its own secretion without intermediate steps or other hormones. Dysregulation in the ultra-feedback mechanism can result from diseases such as Graves’ disease.
What is the ultrashort feedback mechanism?
The regulatory circuit is critical for the paracrine secretion mode in addition to the autocrine secretion modes. Autocrine hormones inhibit or stimulate the secreting gland cell. Glands and glandular cells produce secretions. They are either endocrine or exocrine in nature. Endocrine glands produce hormones or hormone-like substances that are released into the body through various modes of secretion. To keep the budget in balance, the secretion of glandular cells in the human organism is regulated by various regulatory circuits. One of these regulatory circuits is the so-called ultrashort feedback mechanism, which plays a role especially for endocrine secretion. In this control loop, a hormone inhibits its own secretion. In addition to autocrine secretion modes, the regulatory loop is also critical for paracrine secretion modes. Autocrine hormones inhibit or stimulate the secreting gland cell. In paracrine hormone secretion, the hormone binds to the receptors of tissues in the immediate vicinity. In the ultrashort feedback mechanism, regulation occurs without the intermediate step of another hormone. This distinguishes the feedback loop from other regulatory mechanisms. Other physiological feedback loops include short-feedback, long-feedback, or ultralong-feedback.
Function and task
Control loops establish equilibrium in physiological milieus. In the endocrine system in particular, this balance is crucial because individual hormone secretions influence each other. Thus, the misregulation of a single hormone can throw the entire hormonal balance out of balance and cause numerous complaints that can even have life-threatening consequences. In addition to hormonal balance, the regulatory circuit of the ultrashort feedback mechanism regulates immunological processes and individual processes at synapses of excitable cells. In the hormonal field, for example, an ultrashort feedback mechanism underlies LH and FSH secretion. The autoregulatory properties in the incretion (internal secretion) of the hypothalamic hormones GnRH and galanin are also due to the mechanism. A less typical ultrashort feedback is the regulatory circuit of CRH secretion in the hypothalamus. Here, the ultrashort loop shows up as a positive feedback loop, allowing CRH to inhibit its own secretion during stress. One of the best known and most typical examples of the ultrashort feedback mechanism is the Brokken-Wiersinga Prummel regulatory loop, which results in auto-inhibition of the TSH hormone. The regulatory mechanism is also referred to as the Prummel-Wiersinga regulatory circuit. Pituitary TSH binds to thyrotropin receptors located on folliculostellar cells in the tissue of the anterior pituitary in this ultrashort feedback mechanism. Presumably, this inhibits the secretion of TSH in all thyrotropic cells via thyrostimulin. This regulatory circuit corresponds to a segment of the thyrotropic regulatory circuit and not only prevents excessive TSH secretion, but also gives the TSH level pulsatility (pulsatility). Any ultrashort mechanism in the human body can theoretically fail or be misregulated by disease processes, thus upsetting hormone balance. Thus, failed ultrashort feedback can be symptomatic in the context of various diseases. One of the best-known examples of a disease affecting ultrashort feedback is Graves’ disease.
Diseases and conditions
Like all dysregulations in the hormonal field, Graves’ disease manifests itself in a variety of complaints and affects various processes in the patient’s body. The disease is an autoimmune thyreopathy associated with HLA-DR3 and other autoimmune disorders. The leading symptom of Graves’ disease is excessive antibody production on the follicular cells of the thyroid gland. These antibodies correspond to the IgG type and mimic the action of TSH. The TSH receptors of the thyroid gland are thus strongly and permanently stimulated.The ultrashort feedback mechanism is thus no longer capable of autoregulation of hormone production. The continuous stimulation of the TSH receptors leads to a chronic growth stimulus that favors goiter. This is a pathological enlargement of the thyroid gland associated with hyperfunction of the organ. The glandular cells henceforth secrete excessive amounts of T3 and T4. With this secretion they cause thyrotoxicosis. Due to the external binding of the antibodies produced, endocrine orbitopathies or pretibial myxedema also develop outside the thyroid gland. Due to the dysregulations in the TSH regulatory circuit, the secretion of the TSH hormone is also suprimed by antibodies in the pituitary gland suppressing individual TSH receptors. In addition to weight loss despite increased appetite, diarrhea, hyperhidrosis, polydipsia, and heat intolerance, symptoms may include tremor, decreased performance, or restlessness. Since the thyroid hormone also has an effect on the cardiovascular system, cardiac arrhythmias often develop in addition. Hair may fall out and muscles may ache. Knowledge of the ultrashort feedback mechanism for autoregulation of TSH is important for the physician in Graves’ disease, especially for interpretation of TSH levels. Patients with Graves’ disease have lower TSH levels because their TSH receptor autoantibodies bind to the TSH receptors and thus act directly in the pituitary gland. Thus, they inhibit the release of TSH through euthyroidism in the sense of immunogenic TSH suppression. Thus, although a significantly higher TSH level would be expected in view of the low FT4 concentrations in the patients’ blood, their level remains decreased. The treatment of hyperthyroidism in Graves’ disease thus proves to be a tightrope walk, and the TSH level can no longer be used as an exclusive criterion for assessing the current metabolic situation. The treating physician must address this in order to follow an appropriate path of therapy and to correctly assess the success of therapy.