Hormone negative feedback control

When the concentration of the free form of a hormone decreases, then more of this hormone will be released from the binding proteins. The free hormone is the biologically active form. It binds to the target tissue to cause its actions and is involved with the negative feedback control of its secretion. The binding of hormones to plasma proteins has several beneficial effects, including ... 

Thyroid hormone production is regulated by TSH secreted by the anterior pituitary, which in turn is under negative feedback control by the circulating level of free thyroid hormone and the positive influence of hypothalamic thyrotropin-releasing hormone. Thyroid hormone production is also regulated by extrathyroidal deiodination of T4 to T3, which can be affected by nutrition, nonthyroidal hormones, drugs, and illness. 

There are also a few examples of positive feedback mechanisms in the endocrine system.25 43 In a positive feedback loop, rising concentrations of one hormone cause an increase in other hormones, which, in turn, facilitates increased production of the first hormone. The primary example of this type of feedback occurs in the female reproductive system, where low levels of estrogen production increase the release of pituitary hormones (LH, FSH).10 43 Increased LH and FSH then facilitate further estrogen production, which further increases pituitary hormone secretion, and so on (see Chapter 30). Positive feedback mechanisms are relatively rare, however, compared with negative feedback controls in the endocrine system. 

FIGURE 28-1 Negative feedback control in the hypothalamic-pituitary-endocrine pathways. Excitatory and inhibitory effects are indicated by (+] and H, respectively. Negative feedback loops occur owing to inhibition of the endocrine hormone on the pituitary and hypothalamus. 

FIGURE 29-2 Negative feedback control of glucocorticoid synthesis. Cortisol limits its own synthesis by inhibiting the release of corticotropin-releasing hormone [CRH] from the hypothalamus and adrenocorticotropic hormone [ACTH] from the anterior pituitary. 

Thyroid hormone release is subject to the negative feedback strategy that is typical of endocrine systems controlled by the hypothalamic-pituitary axis. Increased circulating levels of the thyroid hormones (T4, T3) serve to limit their own production by inhibiting TRH release from the hypothalamus and TSH release from the anterior pituitary.30,35 This negative feedback control prevents peripheral levels of thyroid hormones from becoming excessively high. 

Figure 18.3. Endocrine-immune inter-relationship in depression. In depression, the hypothalamic-pituitary-adrenal (HPA) axis is up-regulated with a down-regulation of its negative feedback controls. Corticotrophin releasing factor (CRF) is hypersecreted from the hypothalamus and induces the release of adrenocortico-trophic hormone (ACTH) from the pituitary. ACTH interacts with receptors on adrenocortical cells and cortisol is released from the adrenal glands adrenal hypertrophy can also occur. Release of cortisol into the circulation has a number of effects, including elevation of blood glucose. The negative feedback of cortisol to the hypothalamus, pituitary and immune system is impaired. This leads to continual activation of the HPA axis and excess cortisol release. Cortisol receptors become desensitized leading to increased activity of the pro-inflammatory immune mediators and disturbances in neurotransmitter transmission.

Steger RW, Silverman AY, Siler-Khodr TM, Asch RH (1980) The effects of A9-tetrahydro-cannabinolon the positive and negative feedback control of luteinizing hormone release. Life Sci 27 1911-1916... 

Disappearance of the negative feedback control of hormones leads to uncontrolled hormone secretion. For example, ovarian failure—as it happens in menopause—is caused by the luteinizing hormone and follicle-stimulating hormone levels increase due to the lack of negative feedback effects of the gonadal hormones. 

Cholesterol biosynthesis is affected by dietary and hormonal factors as well as by various external influences. Cholesterogenesis is enhanced by radiation, thyroid hormones, hypophysectomy, various metal ions and surface active agents. Biosynthesis is inhibited by fasting, thyroidectomy, vanadium salts, and by feeding of cholesterol or some of its steroid precursors. These influences were reviewed by Kritchevsky et al. (1960). In most cases cholesterol synthesis from acetate is more severely inhibited than is synthesis from mevalonate, suggesting that the inhibition occurs at an early step in cholesterol biosynthesis. The inhibition of cholesterol biosynthesis by cholesterol feeding was shown to possess the characteristics of a negative feedback control system (Bucher et al., 1959). 

Adrenal hormone production is controlled by the hypothalamus and pituitary gland. Corticotropin-releasing hormone (CRH) is secreted by the hypothalamus and stimulates secretion of adrenocorticotropic hormone (ACTH), also known as corticotropin from the anterior pituitary. ACTH, in turn, stimulates the adrenal cortex to produce cortisol. When sufficient or excessive cortisol levels are reached, a negative feedback is exerted on the secretion of CRH and ACTH, thereby decreasing overall cortisol production. The control of adrenal androgen synthesis also follows a similar negative-feedback mechanism. 

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