Normal and Altered Endocrine System Function Normal Endocrine System Function

The timing of reproduction is thought to be under the direct control of the hypothalamus of the brain (for an in-depth discussion see [26, 27]) (Fig. 1). Pulsatile secretions from the hypothalamus of gonadotropin releasing hormone (GnRH) are known to induce the synthesis and release of gonadotropins (GtHs) from the pituitary. In most vertebrates, these gonadotropins are called follicle-stimulating hormone and luteinizing hormone (FSH and LH, respectively) because of their original association with ovarian follicle development and the beginning of the luteal or postovulatory phase in mammals. GtHs are carried in the blood to the gonads, where they induce production of steroid hormones, such as progestins, androgens, and estrogens, as well as gamete growth and differentiation. Androgens and estrogens play a major role during sexual differentiation of the embryo [28]. In the adult, these steroid hormones are responsible for the formation of gametes and development of secondary sex characteristics including reproductive behavior [26, 27]. Steroid hormones are lipophilic and do not dissolve easily in water. A very small percentage of the hormones are free in the blood, and most are carried bound to serum binding proteins (SBPs), such as sex hormone binding globulin. Hormones bound to SBP are protected

Fig. 1. Four hierarchical levels of endocrine system function include control (hypothalamus and pituitary of the brain), production (gonad), availability (steroid hormone metabolism/ xenobiotic detoxification and serum binding protein synthesis in the liver), action (receptors in the brain, gonad, and liver). The potential for alteration of steroid hormone concentration exists at each of these levels

Fig. 1. Four hierarchical levels of endocrine system function include control (hypothalamus and pituitary of the brain), production (gonad), availability (steroid hormone metabolism/ xenobiotic detoxification and serum binding protein synthesis in the liver), action (receptors in the brain, gonad, and liver). The potential for alteration of steroid hormone concentration exists at each of these levels from degradation by the liver and are also thought to function as a reserve of available hormone. The concentration of SBPs and the rate of degradation and excretion from the organism regulate the availability of steroid hormones to their target tissue [22, 29, 30]. Hormone action, thus a biological response, results from the binding of a hormone with its receptor (Fig. 2). Most commonly, steroid hormones move through the cell membrane and bind intracellular receptors. This hormone-receptor complex attaches to a particular site on the DNA (hormone response elements) and induces transcription [26]. Recently, membrane-bound steroid hormone receptors have been discovered [31-35]. Various nongenomic functions, such as ion channel regulation and enzyme activation, have been proposed as additional functions for steroid hormones. In summary, the brain controls steroid synthesis, steroid production is in the go-nads, the liver regulates steroid availability, and steroid action is a function of receptor location.

There are several axes that are under the control of the hypothalamus - pituitary regions of the brain. These include the reproductive, growth, thyroid, and stress axes (Fig. 3).Any chemical that can mimic an endogenous compound has the potential to interact with and potentially disrupt the normal functioning of any of these axes. In addition, there are two nonsteroid hormone members of the nuclear receptor superfamily: retinoic acid and vitamin D3.Both systems have been shown to have the potential for disruption by xenobiotics [36].

Ciclo Vida Rana

Fig. 2. Steroid hormone action depicted at the cellular level. Most of the steroid hormones are transported in the blood bound to serum binding proteins, whereas most endocrine disrupting chemicals (EDCs) that have been examined circulate freely. Both steroid hormones and EDCs can bind to membrane-bound or intracellular receptors. Membrane-bound receptors help regulate cellular activity and provide a rapid response to changes in the extracellular environment. Intracellular receptors regulate transcription and the response period is relatively slower compared to the action of the membrane-bound receptors

Fig. 2. Steroid hormone action depicted at the cellular level. Most of the steroid hormones are transported in the blood bound to serum binding proteins, whereas most endocrine disrupting chemicals (EDCs) that have been examined circulate freely. Both steroid hormones and EDCs can bind to membrane-bound or intracellular receptors. Membrane-bound receptors help regulate cellular activity and provide a rapid response to changes in the extracellular environment. Intracellular receptors regulate transcription and the response period is relatively slower compared to the action of the membrane-bound receptors

These hormone systems do not work in isolation, but cross talk or interaction between these axes is known to occur, and together they control development and reproduction in an organism [37,38].

The potential for endocrine system disruption is complex and can occur in different organs (e.g., the hypothalamus, pituitary, and gonad and liver), and at different biochemical levels (e.g., receptors, serum binding proteins, enzymes for synthesis or degradation, hormone response elements) [35, 36]. Given the fact that endocrine axes are related by their interactive effects on both develop-

Environmental Signals

Naturally occuring Human introduced

AXES

BRAIN

HYPOTHALAMUS

tropin-releasing factors PITUITARY GLAND

tropins

TARGET TISSUE

SERUM BINDING PROTEINS

INTERNAL SIGNALS

hormones

ORGANISM

Stress

Thyroid

Reproduction Growth

CRH 1

ACTH i

CBG 1

Adrenal tl-^jj Interrenal Thyroid

TBG 1

T4 T3

GnRH

1 GtH

Gonads

SHBG

GHRH 1

GH 1

, Liver

Development and Reproduction

Fig. 3. These four endocrine axes (stress, thyroid, reproductive, and growth) are related because they control the development and reproduction in a typical vertebrate. Each of these axes integrates external signals from the environment, transduced by the hypothalamus and pituitary of the brain, into internal signals or hormones produced by the target tissues. EDCs have the potential to alter the normal function of any of these axes. Furthermore, since these axes are known to interact, modification of one axis could affect another axis ment and reproduction, the disruption of one axis could impact another axis (e.g., the stress axis and its effect on the reproductive axis [39]).

Body Detox Made Easy

Body Detox Made Easy

What exactly is a detox routine? Basically a detox routine is an all-natural method of cleansing yourbr body by giving it the time and conditions it needs to rebuild and heal from the damages of daily life and the foods you eat and other substances you intake. There are many different types of known detox routines.

Get My Free Ebook


Post a comment