Drugs Affecting Endocrine Function

Although the detailed features of the interactions involved in cortisol secretion are still unknown, some observations indicate that the irregular behavior of cortisol levels originates from the underlying dynamics of the hypothalamic-pituitary-adrenal process. Indeed, Ilias et al. [514], using time series analysis, have shown that the reconstructed phase space of cortisol concentrations of healthy individuals has an attractor of fractal dimension dj = 2.65 0.03. This value indicates that at least three state variables control cortisol secretion [515]. A nonlinear model of cortisol secretion with three state variables that takes into account the simultaneous changes of adrenocorticotropic hormone and corticotropin-releasing hormone has been proposed [516]. 

The Model These observations prompted us to model cortisol plasma levels [517] relying on the well-established erratic secretion rate [518] and the circadian rhythm, while other factors controlling cortisol secretion are also considered but not expressed explicitly  

Our dynamic model consists of (11.12) and (11.13). The physical meaning of the time delay in (11.12) is that the cortisol concentration c(t) affects other physiological parameters of the hypothalamic-pituitary-adrenal process (not present in equation 11.12), which in turn affect, via the feedback mechanism, cortisol concentration thereby cortisol controls its own secretion [438]. This cycle is postulated to last time t°, and that is how the concentration c° (t) at time t — t° arises. 

The value assigned to t° corresponds to about one cortisol secretion burst per hour in accordance with experimental observations [518]. The simulations were performed by a numerical solution of (11.12) and (11.13). This simulation exhibits the circadian rhythm, as well as the pulsatile nature of the cortisol secretion system. 

As we have already mentioned (cf. Chapter 3), one of the most important features of nonlinear dynamics is the sensitivity to initial conditions. A measure to verify the chaotic nature of a dynamic system is the Lyapunov exponent [32], 

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Compounds Affecting Rq>roduction Compounds that can affect reproductive function include several drugs and occupationally important chemicals such as solvents and pesticides as well as a number of environmentally relevant com-fxrunds. A group of chemical compounds that has received much attention recently is endocrine disrupters, many of which are halogenated hydrocarbons, e.g., PCBs. These are known to induce feminization in fish and other animal species.1.5/ There is intense debate about the significance of these compounds to human health. Tobacco smoke and ethyl alcohol also have major effects on human reproduction, the effects of alcohol being especially important. Table 5.17 lists compounds that may disturb the functions of female and male reproductive functions. 

Roti E, Gnudi A, Braverman LE, The placental transport, synthesis and metabolism of hormones and drugs which affect thyroid function. Endocrine Rev 4 131 (1983)... 

Drug/Lab test interactions Certain endocrine and liver function tests may be affected by estrogen-containing OCs. Expect these similar changes with larger doses Increased sulfobromophthalein retention. 

L-Tyrosine metabolism and catecholamine biosynthesis occur laigely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andUpid metabolism. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bile acids and the detoxification process of aromatic drugs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabolism related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

In vitro, the capillary endothelial cells of the pancreas are still attached to the outer rim of whole islets postisolation and, with conditioned medium, may be coaxed to proliferate outward onto extracellular matrix-coated plastic plates for further mechanistic studies and functional analyses. The isolated capillary endothelial cells can be characterized by examining a-1 proteinase inhibitor and nephrin expression via immunocytochemistry or flow cytometry (Zanone et al., 2008). Not only do these endothelial cells play a role in drug candidate-induced effects on insulin secretion and glucose regulation of islets, but they also act as the regulators of leukocyte recruitment into the islets. The pancreatic microvasculature is therefore likely to play a role in the altered physiology of the endocrine and exocrine pancreas if affected by drug candidate exposure. 

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