Endocrine system feedback

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-... 

GHRF and GHRIF are peptides secreted by hypothalamic neurons termed neuroendocrine transducers (the name is apt, as these interface between the nervous and endocrine systems). The factors that regulate their secretion are poorly understood but probably involve both nerve impulses originating from within the brain and feedback mechanisms, possibly involving pituitary hormones. 

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. 

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 ... 

In summary, PCBs can affect a wide variety of endocrine systems by directly affecting the components of the endocrine system such as hormones, metabolic enzymes, carrier proteins, receptors, endocrine glands, and feedback regulation systems. Effects on these components can lead to alterations in neurodevelopment, reproduction, and in induction of endocrine-sensitive tumors. 

The endocrine system is complex, involving many glands and hormones, which are interconnected by feedback mechanisms. The pituitary gland and the hypothalamus produce hormones that affect the activity of many other glands. There are many disorders of the endocrine glands. 

ENDOCRINE SYSTEM A number of endocrine tissues respond to PGs. In a number of species, the systemic administration of PGE increases circulating concentrations of adrenocorticotropic hormone (ACTH), growth hormone, prolactin, and gonadotropins. Other effects include stimulation of steroid production by the adrenals, stimulation of insulin release, and thyrotropinlike effects on the thyroid. The critical role of PGF in parturition relies on its ability to induce an oxytocin-dependent decline in progesterone levels. PGE works as part of a positive-feedback loop to induce oocyte maturation required for fertihzation during and after ovulation. 

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 ... 

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. 

Anabolic steroids are not only reinforcing drugs, as are many narcotics, but they also interfere with the normal function of the endocrine system, and as such are endocrine disruptors. The presence of exogenous anabolic steroids in the blood causes a negative feedback in the brain, specifically the hypothalamus and the pituitary. This feedback leads to a reduction in the synthesis of gonadotropins —water-soluble hormones that travel in the blood to the testes, where they stimulate the synthesis of testosterone. This reduction... 

FIGURE 23-11 Cascade of hormone release following central nervous system input to the hypothalamus. In each endocrine tissue along the pathway, a stimulus from the level above is received, amplified, and transduced into the release of the next hormone in the cascade. The cascade is sensitive to regulation at several levels through feedback inhibition by the ultimate hormone. The product therefore regulates its own production, as in feedback inhibition of biosynthetic pathways within a single cell. 

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-... 

Figure 18.2. Endocrine-immune inter-relationship in normal subject. The hypothalamic-pituitary-adrenal (HPA) axis is a feedback loop that includes the hypothalamus, the pituitary and the adrenal glands. The main hormones that activate the HPA axis are corticotrophin releasing factor (CRF), arginine vasopressin (AVP) and adrenocorticotrophic hormone (ACTH). The loop is completed by the negative feedback of cortisol on the hypothalamus and pituitary. The simultaneous release of cortisol into the circulation has a number of effects, including elevation of blood glucose for increased metabolic demand. Cortisol also negatively affects the immune system and prevents the release of immunotransmitters. Interference from other brain regions (e.g. hippocampus and amygdala) can also modify the HPA axis, as can neuropeptides and neurotransmitters.

The effect of stress on the endocrine and immune systems depends upon its duration and severity. Following acute stress, the rise in ACTH in response to the release of corticotrophin releasing factor (CRF) from the hypothalamus results in a rise in the synthesis and release of cortisol from the adrenals. The increase in the plasma cortisol concentration results in a temporary suppression of many aspects of cellular immunity. Due to the operation of an inhibitory feedback mechanism, stimulation of the central glucocorticoid receptors in the hypothalamus and pituitary causes a decrease in the further release of CRF, thereby decreasing the further... 

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.

---