The long-feedback mechanism is a principle of feedback as it is relevant to hormone balance in the human body. Among the best-known long-feedback mechanisms is the regulatory loop between thyroid hormones and TSH (thyrotropin). Disturbances within this control loop occur in Graves’ disease, among others.
What is the long-feedback mechanism?
Among the best-known long-feedback mechanisms is the regulatory loop between thyroid hormones and TSH. Feedback mechanisms in the sense of self-regulating feedback play a role in the human body, especially for the hormone system. Hormones regulate their own release during self-adjustment. Different types of feedback exist. One of them is the long-feedback mechanism, which corresponds to a physiological self-adjustment principle. Long-feedback plays a role, for example, in thyroid hormones and their effect on thyrotropin-releasing hormone release. Moreover, the long-feedback mechanism is a basic principle in the central control of the endocrine system. The hypothalamus is at the center of this control. This part of the brain belongs to the diencephalon and corresponds to the highest regulatory center of all vegetative and endocrine processes. Essentially, two circuits play a role in the hormonal control processes by the hypothalamus. In addition to the short-feedback mechanism, the hypothalamic-adenohypophyseal loop or pituitary loop, this includes the adenohypophyseal or pituitary-end-organ loop, which corresponds to a long-feedback mechanism.
Function and task
In the human body, different regulatory principles with feedback mechanism exist, so mainly within hormonal regulation. Different feedback levels are involved in this regulation. The hypothalamus is the top center of all hormonal feedback processes. The brain area contains receptive areas that receive information from the environment, from the central nervous system, and from the hormonal body periphery. The information from the body periphery usually corresponds to changes in hormone concentration. The totality of the above information is registered by the receptive fields of the hypothalamus. The connection between the periphery and the hypothalamus represents a long-feedback mechanism. Ultimately, information from the hypothalamus reaches the pituitary gland. This can either occur neurogenically via the tuberohypophyseal tract, or through the portal vasculature via hypophyseotropic hormones. The latter is the case with the releasing hormones and inhibiting hormones of the hypothalamus. These hormones are control hormones that exert a specific effect on the anterior pituitary. Releasing hormones are, for example, the hormones GHRH, GnRH, CRH and THR. Feedback information is received by the hypothalamus from the pituitary gland via a short-feedback mechanism rather than a long-feedback mechanism. The long-feedback mechanism between the hypothalamus and periphery also plays a role for glandotropic hormones, which are themselves an important regulatory principle within endocrine feedback. Because the pituitary gland also receives feedback information from the body periphery through a long-feedback mechanism, the gland can regulate the secretion of glandotropic hormones based on this information and thus influence the secretion of peripheral endocrine organs. Accordingly, the hypothalamic-pituitary system has multiple feedbacks and determines the activity of all glands by using the regulatory principle of glandotropic hormones. All regulatory stages of the system are controlled in terms of negative feedback. In short, the hormonal household is organized in regulatory circuits that continuously adapt to the current hormonal needs of the body. The hypothalamic-pituitary axis is the most essential example of this principle. The long feedback mechanism thus ultimately plays a role for all hormones and is ultimately also relevant for ovulation, for example. The long feedback effect of estrogens and progesterone is again retroactively related to the hypothalamic-pituitary system. Thus, the female cycle has two important control components. In addition to the long loop feedback of estrogens and progesterone on the system between hypothalamus and pituitary gland, the pulsatile release of the hormones GnRH, LH and FSH plays a role for ovulation.
Diseases and ailments
Due to the close interrelationships of individual control circuits, the disruption of a single hormone control circuit usually leads to the disruption of the entire hormone balance and related body functions. Thus, hyperthyroidism or hypothyroidism (hypero- and hypothyroidism), for example, may result from a deficiency or excess of TSH and thus refer to pituitary dysfunction. The long-feedback mechanism between thyroid hormones and thyrotropin-releasing hormones accounts for this relationship. Similarly, TSH-producing tumors can cause an excess of TRH, which in a sequel disrupts the thyrotropic regulatory circuit. Effects on the long-feedback mechanism between thyroid hormones and TRH are also seen in diseases such as Graves’ disease. In this disease, hyperthyroidism is associated with autoimmunological reactions. The patients’ immune system attacks TSH receptors within the thyroid follicles. Antibodies of the IgG type bind to the receptors and stimulate them permanently by mimicking the action of TRH. This results in increased thyroid activity due to the regulatory circuits. An oversupply of thyroid hormones results. In addition, the gland becomes larger and larger due to growth stimuli. Since the TSH present in the body is ineffective due to its inability to bind to receptors, various bodily functions ultimately become unbalanced. Due to the increased thyroid hormone concentration, the general TSH concentration decreases via the long feedback mechanism. At the same time, autoantibodies on the pituitary gland hinder TSH secretion. Although the TSH concentration decreases continuously, hyperthyroidism is present in the context of the disease. Cushing’s syndrome also leads to disturbances of the entire hormonal system. The disease is a disorder of the hypothalamic-pituitary-adrenocortical axis. Tumors of the anterior pituitary often secrete ACTH, which stimulates high plasma levels of cortisol. Patients suffer from elevated blood glucose levels, which may be associated with type II diabetes mellitus. Furthermore, osteoporotic changes as well as muscle weakness may occur. Truncal obesity with bull neck and full moon face are characteristic signs of Cushing’s syndrome.
