Endocrine system feedback control

Reports of the effects of Li+ upon the thyroid gland and its associated hormones are the most abundant of those concerned with the endocrine system. Li+ inhibits thyroid hormone release, leading to reduced levels of circulating hormone, in both psychiatric patients and healthy controls [178]. In consequence of this, a negative feedback mechanism increases the production of pituitary TSH. Li+ also causes an increase in hypothalamic thyroid-releasing hormone (TRH), probably by inhibiting its re-... 

The nervous system has several properties in common with the endocrine system, which is the other major system for control of body function. These include high-level integration in the brain, the ability to influence processes in distant regions of the body, and extensive use of negative feedback. Both systems use chemicals for the transmission of information. In the nervous system, chemical transmission occurs between nerve cells and between nerve cells and their effector cells. Chemical transmission takes place through the release of small amounts of transmitter substances from the nerve terminals into the synaptic cleft. The transmitter crosses the cleft by diffusion and activates or inhibits the postsynaptic cell by binding to a specialized receptor molecule. In a few cases, retrograde transmission may occur from the postsynaptic cell to the presynaptic neuron terminal. 

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. 

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.

Q10 Many endocrine secretions are controlled by negative feedback systems. When the thyroid is stimulated and thyroid hormone concentration increases, it inhibits production of TSH to reduce further stimulation of the gland. As thyroid hormone secretion then diminishes, the negative feedback on the anterior pituitary is reduced and TSH secretion increases again. Basically, in... 

Hierarchical control and feedback control, both positive and negative, are a fundamental feature of endocrine systems (Figure 13.2). Each of the major hypothalamic-pituitary-hormone axes is governed by negative feedback ... 

When self-regulating physiological systems (generally controlled by negative feedback systems, e.g. endocrine, cardiovascular) are subject to interference, their control mechanisms respond to minimise the effects of the interference and to restore the previous steady state or rhythm this is homeostasis. The previous state may be a normal function, e.g. ovulation (a rare example of a positive feedback mechanism), or an abnormal function, e.g. 

Regulation of Secretion Plasma Ca +is the major regulator of PTH secretion hypocalcemia stimulates and hypercalcemia inhibits PTH secretion. Sustained hypocalcemia also induces parathyroid hypertrophy and hyperplasia. Changes in Ca modulate PTH secretion by parathyroid cells via the calcium-sensing receptor (CaSR), a GPCR that couples with G -PLC and G. Occupancy of the CaSR by Ca inhibits PTH secretion thus, the extracellular concentration of Ca is controlled by an endocrine negative-feedback system, the afferent limb of which senses the ambient activity of Ca and the efferent hmb of which releases PTH that then acts to increase Ca. The active vitamin D metabolite calcitriol directly suppresses PTH gene expression. 

The hypothalamus secretes releasing and inhibitory substances into the anterior pituitary vasculature, thereby regulating anterior pituitary function. Pituitary secretions are also controlled by feedback control via circulating hormones. Endocrine systems influenced by the anterior pituitary are ... 

FIGURE 24.6 A simple feedback control system involving an endocrine gland and a target organ. 

On a whole-body basis, metabolism is controlled by an integrated system consisting of a nervous system with a fixed physical structure and an endocrine system secreting hormones that travel to various target tissues. At the cellular level, control is exerted by manipulation of the active enzyme supply and by feedback inhibition. 

The presence of feedback systems in endocrine function is important from a pharmacologic perspective. Drugs can be administered that act through the intrinsic feedback loops to control endogenous hormone production. A primary example is the use of oral contraceptives, when exogenous estrogen and proges-... 

Many compounds have been implicated as male reproductive toxicants, but their sites and mechanisms of action are not well understood. The classification of male reproductive toxicants as direct or indirect is useful to help define the primary site of toxicity (Figure 6). A direct toxicant would primarily target the testicular cells, the excurrent duct system of the male reproductive tract, or mature spermatozoa. An indirect toxicant would cause reproductive toxicity by acting on hypothalamic/pituitary neuroendocrine controls or on extragonadal systems. Since the testis is subject to hormonal control and feedback loops, the action of indirect toxicants on endocrine homeostasis can ultimately damage testicular cell types. 

Hormones are molecules organisms use to convey information between cells. When target cells are distant from the hormone-producing cell, such molecules are called endocrine hormones. To ensure proper control of metabolism, the synthesis and secretion of many mammalian hormones are regulated by a complex cascade mechanism ultimately controlled by the central nervous system. In addition, a negative feedback mechanism precisely controls various hormone syntheses. A variety of diseases are caused by either overproduction or underproduction of a specific hormone or by the insensitivity of target cells. 

In fact, ACTH secretion is regulated by a neuro-hormonal mechanism and a humoral feedback mechanism. The neurohormonal control of ACTH secretion involves what has been referred to as a third-order neuroendocrine mechanism. Three steps are involved in this control. A stimulus (stress, for example) brings the central nervous system to secrete a hormone (CRF), which acts on another endocrine structure in the anterior lobe of the hypophysis where it induces the secretion of second hormone (ACTH), which ultimately acts on the target endocrine gland—the adrenal cortex [40, 56-60]. 

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