Adrenal Fatigue and Exercise

Adrenal Fatigue Recovery Workbook

This valuable book gives you all of the tools that you need in order to identify, manage, and treat the symptoms of adrenal fatigue syndrome. AFS is a medical problem that most doctors don't really know how to diagnose. The symptoms are often seen as being too vague to mean anything to medical professionals, and therefore people who suffer from this debilitating condition often suffer alone, and without medication. And those that DO get medicated often get put on something useless for this condition such as antidepressants or sleeping pills, which just add issues on to what you are already experiencing. If you are feeling down, tired, or depressed for no reason, there is a good chance that you are suffering from Adrenal Fatigue Syndrome There is no need for you to bear that alone! Why would you want to do that when you have a valuable resource in your hands? This book has everything you need to get help!

Adrenal Fatigue Recovery Workbook Summary

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Adrenal Glands Anatomy

There are two adrenal glands, one situated above each kidney. Both glands have a rich arterial blood supply, mainly from the suprarenal arteries from the aorta, branches from the renal arteries, and branches from the phrenic vessels. The venous drainage is normally by a single vein, on the right side draining directly into the inferior vena cava, and on the left side into the left renal vein.

Adrenal Glands

The adrenal glands are paired organs that cap the superior borders of the kidneys (fig. 11.18). Each adrenal consists of an outer cortex and inner medulla that function as separate glands. The differences in function of the adrenal cortex and medulla are related to the differences in their embryonic derivation. The adrenal medulla is derived from embryonic neural crest ectoderm (the same tissue that produces the sympathetic Figure 11.18 The structure of the adrenal gland, showing the three zones of the adrenal cortex. The zona glomerulosa secretes the mineralocorticoids (including aldosterone), whereas the other two zones secrete the glucocorticoids (including cortisol).

Frank Z Stanczyk Philip Bretsky

In the human body, a balance exists between production and clearance of steroid hormones. Production of steroid hormones occurs de novo by biosynthetic pathways in specific endocrine glands, i.e., the adrenals and ovaries in women and the adrenals and testes in men. In addition, steroid hormones can be produced in peripheral (nonendocrine gland) tissues from circulating precursors that originate from the endocrine glands. Important sites of peripheral steroid hormone formation include the liver, kidney, breast, prostate, and sexual and nonsexual skin. After steroid hormones are secreted by the endocrine glands, they enter the systemic circulation, where they are mostly bound to proteins. The low-affinity bound and non-protein-bound (free) steroids, sometimes referred to as bioavailable steroids, are available for binding to steroid hormone receptors (progestogen, androgen, estrogen, glucocorticoid, mineralocorticoid) and if active, they exert a biological effect. Alternatively, they...

Conversion of Cholesterol to Pregnenolone

The first and rate-limiting step in the biosynthesis of steroid hormones in the adrenals and gonads is the conversion of cholesterol to preg-nenolone (Figs. 2.1, 2.2). This reaction occurs in the mitochondrion and is catalyzed by the cholesterol side-chain cleavage cytochrome P-450 (P450scc) enzyme (also referred to as cholesterol desmolase or cholesterol lyase) in conjunction with auxiliary electron-transferring proteins, located in the inner mitochondrial membrane. This electron-transport system consists of three protein components reduced nicotinamide adenine dinucleotide phosphate (NADPH)-de-pendent reductase (ferredoxin reductase), ferre-doxin, and cytochrome P-450. Electrons are Figure 2.2 Biosynthesis of steroid hormones in the adrenals. Figure 2.2 Biosynthesis of steroid hormones in the adrenals.

Atypical Nuclear Receptors

Several structurally divergent members of the NR superfamily have been isolated. The human gene DAX-1, which lacks a conventional zinc finger DBD, encodes one of these atypical NRs. DAX-1 contains a region consisting of four repeats of alanine and glycine-rich sequences that likely binds DNA. It is responsible for dosage-sensitive sex- and X-linked adrenal hypoplasia, an inherited disorder of adrenal gland develop-ment.68 The LBD of DAX-1 is similar to typical members of the NR superfamily.

Function of Brown

The amount of brown fat in the body is greatest at the time of birth. Brown fat is the major site for thermogenesis (heat production) in the newborn, and is especially prominent around the kidneys and adrenal glands. Smaller amounts are also found around the blood vessels of the chest and neck. In response to regulation by thyroid hormone (see chapter 11) and norepinephrine from sympathetic nerves (see chapter 9), brown fat produces a unique

Glucocorticoid and Mineralocorticoid Receptors

Response, immune function, and mood (Tables 3.4, 3.5). Given the wide array of responses that these hormones (produced primarily by the adrenal gland) elicit, it is not surprising that the GR is expressed widely and that its function has been extensively explored. As discussed above (see Crosstalk Between Nuclear Receptors and Other Transcription Factors), analysis of bona fide target genes for GR has been complicated by the multiple mechanisms of transcriptional control that this receptor exhibits. For gluco-neogenic enzymes, the GR generally activates transcription through positively acting response elements. However, many of the actions of glu-cocorticoids are inhibitory, and this is partially achieved through binding to negative response elements within the promoters for genes such as prolactin and proopiomelanocortin. Most of the antiinflammatory effects of glucocorticoids involve another mechanism of repression, which does not seem to require the DBD of this receptor and...

Other Orphan Receptors

Preliminary analysis of the activities and expression patterns of members of the large family of orphan receptors suggests that many are involved in the regulation of liver-specific metabolism (i.e., HNF-4, PPARa, LXR, FXR, LRH-1, SHP-1, SXR, CAR), while others seem to play roles in steroidogenesis, sexual differentiation, and germ cell development (i.e., TR2, TR4, SF-1, GCNF, NGFI-B, DAX-1) or neural function and specification (ERR, ROR, TLX, photoreceptor nuclear receptor PNR ) (Tables 3.8, 3.9). It is likely that these receptors integrate and regulate gene expression by virtue of regulation of the activities of some of the previously mentioned NRs. Several orphans (COUPs, RevErbA) seem to function exclusively as negative regulators of transcription, silencing in trans or bound to DNA as homodimers, RXR het-erodimers, and even monomers.3 At least one receptor (CAR) is a constitutive activator, whose activity is repressed in a ligand-dependent man-ner.322 Several structurally...

Monoamines as Neurotransmitters

The regulatory molecules epinephrine, norepinephrine, dopamine, and serotonin are in the chemical family known as monoamines. Serotonin is derived from the amino acid tryptophan. Epinephrine, norepinephrine, and dopamine are derived from the amino acid tyrosine and form a subfamily of monoamines called the catecholamines (see fig. 9.8, p. 229). Epinephrine (also called adrenaline) is a hormone secreted by the adrenal gland, not a neurotransmitter, while the closely related norepinephrine functions both as a hormone and a neurotransmitter.

Hormones and sexual behavior in women

It seems convenient to begin the discussion of the human female with a summary of the hormonal changes occurring after puberty. We all know that women have a menstrual cycle, and any introductory physiology and even psychology textbook will provide us with an excellent description of the hormonal changes during the cycle. Suffice to mention that estradiol, the main follicular estrogen, is mainly secreted during the first half of the cycle with a peak around ovulation. Progesterone, produced by the corpus luteum, is elevated from shortly after ovulation until the beginning of menstruation, when it rapidly drops. This is the picture of the menstrual cycle generally divulged in textbooks and on Internet sites. However, in addition to producing estrogens and progesterone, the ovaries also produce androgens. In fact, human female blood contains several androgens, like dehydroepiandrosterone sulphate, dehydroepiandrosterone, androstenedione, testosterone and dihydrotestosterone. The...

The role of androgens in women

In order to observe a reduction in sexual behavior in women caused by androgen deficiency, a large decline in blood concentration appears to be necessary. There are indeed some women whose blood androgen concentration is extremely low. This is the case in women who have been subjected to adrenalectomy in addition to ovariectomy. Not only are the main sources of testosterone suppressed, but also most of the testosterone precursors that normally are transformed into testosterone in peripheral tissues are removed. The adrenal cortex is the main site of synthesis of these precursors, and extirpation of the adrenal will eliminate production of them. In adrenalectomized, ovariectomized women, sexual behaviors are much reduced (Waxenberg et al., 1959) and they can be restored by treatment with androgens. Severe androgen deficiency following treatment with cytotoxic agents in ovariectomized women has also been reported to markedly decrease sexual responsiveness (Kaplan and Owett, 1993). These...

And Parasympathetic Cardiac Controls

The suprarenal glands can also contribute to vasomotion. Because norepinephrine is released directly into the bloodstream from these endocrine glands, arteriolar constriction in the systemic organs can result. The human fight-or-flight response elicited under stressful or exciting circumstances originates within the hypothalamus and via hormones travels to the pituitary gland and later the adrenal cortex, where the agent cortisol is released into the bloodstream and adrenal medulla. It is in the medulla that cortisol activates the enzyme necessary to convert norepinephrine to epinephrine, which is released into the bloodstream to amplify increased sympathetic activity (2,3). Blood flow to the skin and other internal organs (like the stomach and intestines) is greatly decreased by increasing sympathetic (and decreasing parasympathetic) tonic activity flow to skeletal muscles and the heart increases considerably. This process can be thought of as simply delivering blood to the areas of...

Infective Endocarditis

Infective endocarditis is frequently complicated by thrombocytopenia. These patients are also at risk for septic emboli manifesting as thrombotic or hemorrhagic stroke, myocardial infarction, renal infarction, or even acute limb ischemia (de Gennes et al., 1990). Thus, the profile of macrovascular thrombosis and thrombocy-topenia characteristic of HIT can be mimicked, especially as heparin is often used to anticoagulate patients with septic endocarditis (Delahaye et al., 1990). Micro-embolization leading to multiple small infarcts or microabscesses, in such organs as muscles, adrenal glands, and spleen, is an additional feature of endocarditis (Ting et al., 1990) that is not seen in HIT. When endocarditis-associated thrombocytope-nia is unusually severe, potential explanations include platelet-reactive autoantibo-dies (Arnold et al., 2004) or procoagulant monocyte-stimulating factors secreted by microorganisms from within large vegetations (Selleng et al., 2006).

Feedback Control of the Anterior Pituitary

Anterior pituitary secretion of ACTH, TSH, and the gonadotropins (FSH and LH) is controlled by negative feedback inhibition from the target gland hormones. Secretion of ACTH is inhibited by a rise in corticosteroid secretion, for example, and TSH is inhibited by a rise in the secretion of thyroxine from the thyroid. These negative feedback relationships are easily demonstrated by removal of the target glands. Castration (surgical removal of the gonads), for example, produces a rise in the secretion of FSH and LH. In a similar manner, removal of the adrenals or the thyroid results in an abnormal increase in ACTH or TSH secretion from the anterior pituitary.

Hellevi Peltoketo Veli Isomaa Debashis Ghosh Pirkko Vihko

Estrogen and steroid metabolism in the target or surrounding cells therefore determine the availability of estrogens in breast tissue. The ovary is the single primary source of estradiol (E2) in the circulation of premenopausal women, but circulating estrone (E1) and androgens originating from the adrenal gland are also converted to E2 in peripheral tissues such as adipose tissue and muscles, including smooth muscle cells of the vena cava.15-18 Breast adipose and epithelial cells also contain enzymes needed for the production in situ of E2 from circulating precursors,7,16 which may further enhance estrogen action in the tissue. After menopause, in particular, estrogen biosynthesis in peripheral tissues has a major role in estrogen action.19 Finally, nutriment may contain compounds with estrogenic and or antiestrogenic effects.20

Cerebrospinal Fluid Marker Concentrations

Metastatic yolk sac tumor. The patient is a 28-year-old man. In November 1998, he presented to another hospital with a leftside testicular mass 8 cm in diameter. He underwent orchiectomy, but details on histopathology, marker status, and postoperative therapy are not available. In November 2001, he presented to our medical center with cough and shortness of breath. Chest radiography demonstrated multiple pulmonary metastases and a mediastinal mass. A transbronchial biopsy specimen showed an undifferentiated malignancy consistent with yolk sac tumor, as well as elements suggestive of teratoma (A). The serum a-fetoprotein (AFP) concentration was 8,967 ng mL, the human chorionic gonadotropin level was 7 mIU mL, and lactate dehydrogenase was 197 U L. Computed tomography (CT) of the chest, abdomen, and pelvis confirmed the presence of bilateral lung metastases and a mediastinal mass and demonstrated metastases to the liver, spleen, and right adrenal gland (B and C). Magnetic...

Challenges to Fetal Wellbeing Maternal Stress

Of the cortisol in fetal blood is derived from the mother, at least through mid-gestation (Gitau et al, 1998 Kajantie et al, 2003). Thus, it seems reasonable to postulate that the excessive transfer of adrenal corticosteroids is a major mediator of negative effects. It can hamper growth and protein synthesis, with many adverse effects on the immature brain and immune system (Munck et al, 1984). In rodent studies it is often possible to mitigate these effects of stress, and even to nutritional challenges during pregnancy, by removing the mother's adrenal glands or by pharmacological blockade of the actions of corticosteroids (Langley-Evans, 1997).

Diagnosis and Staging

Rapid progress in the 1990s in laparoscopic surgery included the development of laparoscopic ultrasound probes. Laparoscopy provides the advantage of a visual inspection to exclude the presence of extrahepatic disease on the peritoneal surfaces in the abdominal cavity, and laparo-scopic ultrasonography can be performed on the liver and spleen and, in selected instances, on retroperitoneal structures such as the kidneys, adrenal glands, and pancreas. Laparoscopic evaluation and laparoscopic ultrasonography have further reduced the rate of unnecessary exploratory laparotomy and thus increased the proportion of patients who undergo successful hepatic resection at the time of laparotomy. Like intraoperative ultrasonography, laparoscopic ultrasonography reveals small primary or metastatic liver tumors not visualized on preoperative CT or MR imaging studies in up to 15 of patients.

Neuroendocrine Systems

Corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), and gonadotropin-releasing hormone stimulate the release of a further set of glandotropic hormones ( hormones regulating a remote endocrine target gland) into the general circulation. Their binding to specific endocrine cells in the anterior pituitary induces the secretion of adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), and luteinizing hormone follicle-stimulating hormone, respectively. These latter hormones, in turn, trigger the release of glucocorticoids, thyroid hormones, and sex hormones at their endocrine target glands, i.e., the adrenals, the thyroid gland, and the gonads. Hypothalamic neurons containing growth hormone (GH)-releasing factor or the GH-inhibiting hormone (also called somatostatin) regulate pituitary GH secretion. For prolactin, no releasing factor has been discovered, but TRH stimulates prolactin secretion as well. Dopamine secreted by the tuberoinfundibular...

The Hypothalamic PituitaryAdrenal Axis

Cortisol, secreted by the adrenal gland, is a major stress hormone and exerts vital effects on the cardiovascular, immune, and metabolic systems. Cortisol stimulates hepatic gluconeoge-nesis, amino acid, and free fatty acid mobilization and inhibits glucose uptake by muscle and adipose tissues. It furthermore alters immune functions by upregulating the expression of anti-inflammatory proteins and dampening levels of pro-inflammatory substances. However, permanently enhanced HPA axis activity has been linked to health impairments (Charmandari et al, 2004 Puetz, 2008).

The ENS is Derived from the Neural Crest

The restriction of the levels of the premigratory crest that contribute precursors to the ENS raises the possibility that the crest cells in these regions might be predetermined to migrate to the bowel and give rise to enteric neurons and or glia. Such a predestination, however, is not supported by experimental evidence, which indicates instead that premigratory crest cells are pluripotent. For example, when levels of the crest are interchanged so as to replace a region that normally colonizes the gut with one that does not, the heterotopic crest cells still migrate to the bowel and there give rise to neurons the pheno-types of which are ENS-appropriate, not level of origin-appropriate 62, 63 . An analogous process, moreover, is seen when the interchange of crest cells is reversed. Vagal and sacral crest cells give rise to non-enteric neurons in ectopic locations, such as sympathetic ganglia, when they are grafted so as to replace crest cells at other axial levels. Clones derived from...

Treatment of Early Stage Stage I Esophageal Cancer

Noninvasive studies are quite helpful in identifying patients with meta-static disease. At presentation, 25 of patients with esophageal cancer have metastatic cancer. At autopsy, the most frequent locations of metastatic cancer, in decreasing order of incidence, are the lymph nodes (73 ), lung (52 ), liver (42 ), adrenal glands (20 ), bronchus (17 ), and bone (14 ) (Anderson and Lad, 1982). The presence of metastatic cancer is the worst prognostic factor in terms of long-term survival (Table 15-1). The median survival time of patients with metastatic esophageal cancer is less than 7 months. Because of this short survival, surgical resection is seldom performed, even for palliative purposes, in patients with metastat-ic cancer.

Hypothalamic PituitaryAdrenal Axis HPA Interactions

In addition to effects on the anterior pituitary and adrenal cortex via CRH release from the hypothalamus, pro-inflammatory cytokines also affect the anterior pituitary and adrenal cortex directly, resulting in similar end-organ effects (release of corticosterone from the adrenal cortex). For example, IL-6 is synthesized and released within the human adrenal gland itself, promoting glucocorticoid release (Path et al, 2000). The multitude of sites of action allows pro-inflammatory cytokines several pathways of promoting a similar end-organ response so that even if higher level actions of cytokines on hypothalamic or anterior pituitary structures are inhibited (for example, via antagonism by a Th2 cytokine such as IL-10), some level of glucocorticoid release into the circulation is preserved. In turn, glucocorticoid actions on cytokines help to maintain homeostasis via negative feedback loops. For example, cortisol inhibits cellular synthesis and release of pro-inflammatory cytokines,...

Pharmacological Toxicological Effects 51 Pharmacology

Although the effects of synephrine and C. aurantium differ slightly in hemodynamic studies, the relative content of synephrine compared to octopamine and tyramine (at least 100 times more synephrine) in C. aurantium products substantially outweighs the effects of octopamine and tyramine (18). Although synephrine is found endogenously in the adrenal glands (24), the function is still unclear (20). The binding of synephrine to various adrenergic receptors is shown in Table 2.

Wilms tumour gene function in development and differentiation

The wtl gene shows a definable pattern, both temporal and spatial, of expression in the developing kidney. Its expression is first detectable in the intermediate mesenchyme lateral to the coelomic cavity of 13-somite early 9-day embryos, then in the urogenital ridge (early mesonephric tubules). The uninduced metanephric mesenchyme shows wtl expression by 11 days and soon this is followed by enhancement of its expression in the induced mesenchyme of the kidney and markedly in the nephrogenic condensations later in the development of the kidney, it is restricted to the glomeruli (Armstrong et al., 1993). No expression is found in the proximal or distal tubules and loop of Henle. The genital ridge, fetal gonad and mesothelium are other major sites of wtl expression. No expression is found in fetal heart, skin, adrenal gland, stomach, liver, eye or muscle (Pritchard-Jones et al., 1990). The suppression of myogenesis during kidney development may also be a normal function of wtl (Miyagawa...

Androgens And The Androgen Receptor

The testis, which produces testosterone, and adrenal glands, which produce androstenedione, dehydroepiandrostene, and dehydroepiandro-stene sulfate, contribute to the bulk of circulating androgens. These are converted in the prostate or peripherally by 5a-reductase to DHT, which is approximately 10 times more active than testosterone.13

Sexual motivation theoretical framework

Tail Withdrawal Rat

In addition to producing the behavioral responses of approach and withdrawal, incentive stimuli may activate visceral responses mediated by the autonomous nervous system or by the endocrine system. Examples of such actions of incentive stimuli may be the autonomous response of erection produced by an appropriate sexual incentive. Men and male primates and even male rats frequently respond with erection to stimuli emitted by a sexually receptive female. Similarly, negative incentives like an aggressive intruder may produce an endocrine response such as release of corticosteroids from the adrenal gland cortex as well as sympathetic responses such as release of catecholamines from the adrenal medulla and increases in heart rate and blood pressure. Thus, besides producing organized activity in skeletal muscles incentives may, or may not, produce visceral responses of many kinds.

Patterns Of Tumor Spread

Aortocaval

Other sites of bloodborne metastases include the brain, the liver, and bone. Metastases in unusual sites may be identified in patients with both seminomas and NSGCTs. Unusual sites of disease are most commonly seen in relapsed patients who have undergone previous treatment for metastatic disease. It is therefore important that the radiologist be aware of the patient's previous history and current clinical symptoms. Unusual sites include the kidneys, adrenal glands, muscles, spleen, prostate, pericardium, pleura, and peritoneum (Figure 6-7).16

Lymph Node Metastases

CT images showing unusual sites of metastic disease. Unusual sites of metastatic disease. A, Diffuse peritoneal infiltration with omental cake in a case of nonseminomatous germ cell tumor (NSGST). B, Bilateral adrenal gland involvement from relapsed semi-noma. C, Right psoas muscle metastasis from an NSGCT. D, Pleural disease from disseminated seminoma. Figure 6-7. CT images showing unusual sites of metastic disease. Unusual sites of metastatic disease. A, Diffuse peritoneal infiltration with omental cake in a case of nonseminomatous germ cell tumor (NSGST). B, Bilateral adrenal gland involvement from relapsed semi-noma. C, Right psoas muscle metastasis from an NSGCT. D, Pleural disease from disseminated seminoma.

The importance of testicular hormones in men

They were normally offered a penalty rebate if they accepted castration. This practice was considered inhumane in many societies and castration is almost never performed anymore. In Norway, the procedure may still be legally performed after demand by the individual and approval by a committee, but no demand for castration has been presented since 1974. The situation is probably similar in many other countries. During the first half of the last century, though, castration of sexual offenders was regularly performed in Europe and some scientists profited from this to evaluate sexual behavior in these long-term castrates. It should be noted that all these castrations were performed post-pubertally. Thus, we do not know what the effects of prepubertal castration might be. Data from studies of castrated men in several European countries are unequivocal in the way that they all show that the intensity of sexual behaviors, including sexual dreams and fantasies, was much reduced (e.g....

Latent Viral Genome Load Defining the Risk of Recurrence

The mouse model has revealed that infection history matters (Reddehase et al. 1994). Mice infected as neonates within 24 h after birth showed delayed clearance of acute, productive infection in organs and prolonged persistence in the salivary glands, whereas fully immunocompetent mice infected as adults rapidly controlled acute infection in all organs and showed a shortened persistence in the salivary glands. Months later, during replicative latency, this different history of primary infection was reflected by high or low load of viral genomes, respectively, in organs including lungs, spleen, heart, kidney, adrenal glands, and salivary glands. Importantly, viral DNA load is a predictor of the risk of virus recurrence after hematoablative total-body y-irradiation, with high or low load predicting high or low incidence of recurrence, respectively. Recurrence turned out to be a focal and stochastic event occurring independently in different latently infected organs, thus leading to all...

T187m R227q F234l F194l

Several other androgen-signaling genes have been preliminarily studied in the context of prostate cancer risk. Testosterone is synthesized from cholesterol in a series of enzymatic steps involving several of the cytochrome P-450 enzymes.64 The enzyme cytochrome P-450c17 catalyzes two sequential reactions of the biosynthesis of T, in both the gonads and the adrenals. The first step is the conversion of pregnenolone to 17-hydroxypregnenolone (hydroxylase activity), and the second is its subsequent conversion to C19 steroid dehydroepiandrosterone (lyase activity), a steroid with androgenic activity.64 The CYP17 gene on chromosome 10 encodes the P-450c17 enzyme involved in these two sequential reactions in T biosynthesis.65 A T-to-C transition SNP exists in the 5'-UTR of the CYP17 gene (A2 allele).66 While the functional relevance of this polymorphism is in dispute, it has been linked to polycystic ovarian cancer risk in women, male pattern baldness in men,66 various estrogen metabolic...

Cell Tropism of Other Cytomegaloviruses

Under conditions of severe immunosuppression, murine CMV-infected cells were found in lung, liver, spleen, kidneys, adrenals, gastrointestinal tract, brain, salivary gland, and fibroblasts, epithelial cells, neuronal cells, glial cells, ependy-mal cells hepatocytes and endothelial cells were identified as predominantly infected cell types within these tissues (Reddehase et al. 1985 Podlech et al. 1998 van Den Pol et al. 1999 Podlech et al. 2000). Likewise, a broad target cell range including fibroblasts, SMC, EC, macrophages was found with rat CMV (Kloover et al. 2000 van der Strate et al. 2003 Streblow et al. 2007).

Regulation of Cholesterol to Pregnenolone Conversion

Calcium as intracellular messengers.12 Steroid hormone biosynthesis in the adrenals is stimulated by the pituitary hormone corticotropin, which binds to its receptor at the cell surface and activates adenyl cyclase to increase intracellular cAMP. The latter compound serves as an intracellular messenger to transduce both the acute and the long-term effects of corticotropin. Following the conversion of cholesterol to preg-nenolone by the mitochondrial side-chain cleavage system, the adrenals and gonads can transform pregnenolone to either progesterone or 17a-hydroxypregnenolone. The formation of progesterone from pregnenolone is catalyzed by the enzyme 3jS-hydroxysteroid oxidoreductase commonly referred to as 3j6-hydroxysteroid dehydrogenase (3jS-HSD) in combination with A5,4-iso-merase, in the presence of the cofactor (NAD + ). In addition, 3jS-HSD catalyzes the formation of other A4-3-ketosteroids from corresponding A5-3j6-hydroxysteroids, which leads to the formation of androgens,...

Pharmacological Toxicological Effects

Pseudohypericin has been shown to be a corticotropin-releasing factor (CRF)X receptor antagonist. CRF has been implicated as a pathogenic factor in affective disorders, with elevated levels that are normalized after treatment with antidepressants found in the cerebrospinal fluid of patients with depression. CRF acts on CRF1 receptors in the pituitary gland to stimulate the release of adrenocoticotropic hormone, which stimulates the release of glu-cocorticoid stress hormones from the adrenal glands (19). It is possible that St. John's wort's activity comes from pseudohypericin's ability to block the CRF1 receptor.

The Retroperitoneum

The body wall branches are segmental arteries in series with the posterior intercostal branches of the thoracic aorta.4 The inferior phrenic arteries supply the diaphragm and may send a branch to the adrenal gland. There are four pairs of lumbar arteries, which arise from the posterior abdominal aorta at the bodies of the four upper lumbar vertebrae. They pass laterally and posteriorly against the bodies of the vertebrae, posterior to the sympathetic trunk and posterior to the inferior vena cava on the right side as well.4 The anterior branches of the lumbar arteries are small and barely extend beyond the lateral border of the muscu-lus quadratus lumborum. Each artery also has a large posterior branch that accompanies the dorsal ramus of the corresponding spinal nerve and divides into spinal and muscular branches. The spinal branch passes through the intervertebral foramen and supplies the Branches of the abdominal aorta to paired viscera are the middle adrenal (suprarenal) arteries,...

Organ Development

Many organs, including the heart, liver, spleen, and adrenal glands, are undersized in germ-free rodents. Blood volume is decreased in these animals, perhaps leading to the decreased cardiac output and peripheral blood flow observed (Berg 1996 Savage 1977). Germ-free animals compared to those either conventionally raised or colonized with known species of bacteria show many differences in intestinal anatomy and morphology. Germ-free animals have decreased intestinal mass and surface area, thinner villi, and decreased rates of peristalsis. Intestines show compromised development of the vasculature (Stappenbeck et al. 2002) and abnormalities in glycosylation patterns, mucin production, and proliferation and differentiation of epithelial cells (Banasaz et al. 2002 Gordon et al. 1997). It is not currently known how the commensal microflora mediates these developmental changes.

Hydroxylase

The CYP11B isoenzymes are mitochondrial cytochrome P-450 enzymes. CYP11B1 is expressed at high levels and CYP11B2 at low levels in normal adrenal glands.70 The latter isoenzyme is dramatically increased in aldosterone-secreting tumors. In vitro studies show that both isoenzymes can convert DOC and 11-deoxycortisol to corticosterone and cortisol, respectively.

Fibroblasts

Fibroblasts are not only the standard cell culture system for propagation of HCMV to high titers (Mocarski et al. 2006), but they are also among the major targets of HCMV in vivo (Sinzger et al. 1995). Efficient replication in such a ubiquitous cell type opens the possibility for HCMV to replicate in virtually every organ. Consequently, infected connective tissue cells are assumed to contribute to efficient spread of HCMV in organs as different as adrenal glands, bone marrow, heart, kidney, liver, lung, pancreas, placenta, small bowel and spleen (Bissinger et al. 2002). If the particular property of cultured fibroblast to generate and release high titers of viral progeny also applies for infected connective tissue cells in vivo, then they might contribute greatly to the highly dynamic proliferation of HCMV during acute infections (Emery et al. 1999).

Conclusions

Although pathways of steroid hormone biosynthesis in the adrenals, ovaries, and testes have been known for a number of years, recently only have we begun to understand how genes control the enzymes associated with these pathways. Even less is known about how genes control the enzymatic steps involved in steroid metabolism. This is due to the fact that there are so many metabolites formed, as evident in the discussion on estrogens. Large interindividual differences exist in the metabolism of steroid hormones, which may be reflected in interindividual differences in estrogen action. The formation of so many metabolites raises the question of why it is necessary for the human body to form all of these metabolites. The usual answer to this question is that it is nature's way of detoxifying potent biologically active hormones. However, the metabolites might have important but unrecognized biological effects that are necessary for the action of some hormones. A clearer picture of the...

Ghsr Expression

The expression patterns of the type 1a and type 1b GHS-Rs were studied by ribonu-clease protection analysis in human and rat tissues and by in situ hybridization histochemistry in rhesus hypothalamus and rat brain and pituitary. Functional assessment of sucrose gradient-fractionated poly (A)+ mRNA from swine pituitary gave a single peak of GHS-R activity in the size range 1.6-2.3 kb (Fig. 7). However, attempts at detecting GHS-R mRNA by Northern blotting analysis have been unsuccessful, even though control mRNAs for other GPC-Rs could easily be detected. The authors attribute the difficulty in detecting GHS-R mRNA by Northern blotting analysis to its low abundance and potential size heterogeneity. TRH and GnRH receptors were also readily detected functionally. PCR amplification of the swine pituitary GHS-R cDNA sequences from among 11 pools of an unamplified pituitary cDNA library (110,000 individual cDNAs pool) resulted in GHS-R cDNA identification in only 4 of 11 pools. Therefore,...

And Disease

The overexpression of EPO occurs in a number of adaptive and pathologic conditions. In response to acute hypoxic stress, such as severe blood loss or severe anemia, EPO production can increase 100- to 1000-fold, although the maximal bone marrow response to such stimulation is only a 4- to 6-fold increase in RBC production (46). Overproduction of EPO with accompanying erythrocytosis may be an adaptive response to conditions that produce chronic tissue hypoxia, such as living at high altitude, chronic respiratory diseases, cyanotic heart disease, sleep apnea, smoking, localized renal hypoxia, or hemoglobinopathies with increased oxygen affinity (21). Paraneoplastic production of EPO from tumors and cysts, including renal carcinomas, benign renal tumors, Wilms' tumors, hepatomas, liver carcinomas, cerebellar hemangioblastomas, adrenal gland tumors, and leiomyomas, can also result in high plasma concentrations of the hormone.

Dax1 Shp1

Phenotypes of homozygous null mutations of the indicated mouse receptor genes are summarized where available, as are expression patterns for individual receptor genes. NGFI-B, nerve growth factor induced receptor B Nurr1, Nur related receptor 1 NOR, neuron derived orphan receptor COUP-TF, chicken ovalbumin upstream promoter transcription factor HNF4, hepatocyte nuclear factor 4 TR2 TR4, testis receptor 2, 4 GCNF, germ cell nuclear factor SF-1, steroidogenic factor 1 FTZ-F1, fushi tarazu factor 1 LRH1, liver receptor homolgous protein 1 ERR, estrogen related receptor ROR, retinoic acid related orphan receptor TLX, tailless related receptor X DAX-1, dosage sensitive sex reversal adrenal hypoplasia X chromosome region 1 SHP, small heterodimer partner AG, adrenal gland, THY, thymus PHN, paraventricular hypothalamic neuron CNS, central nervous system H, heart L, liver, LU, lung K, kidney I, intestine TS, testis OV, ovary G, gonads LY, lymph B, bone EMC, extraskeletal myxoid chondrosarcoma...

DNA viruses

Burkitt's lymphoma first presented as a maxillary tumour, initially believed to be a localized granuloma or round-cell sarcoma, but with recognition that deposits were present also in kidneys, adrenals and ovaries, the condition was identified as an unusual form of lymphoma. The tumour occurs only in a belt north and south of the equator where there is a high rainfall and very high levels of malarial infections. The discovery of EBV in cells cultured from Burkitt's lymphoma suggested that this was the causative agent, but the disease can occur in its absence. Furthermore, EBV infection affects 95 of the world population. The restricted geographical distribution of Burkitt's lymphoma implicates a cofactor and this is believed to be constant antigen stimulation from malarial infection stimulating the continuous recruitment of new B-cells which, under the influence of virus, avoid programmed cell death.

Cardiac Denervation

Cardiac denervation results in a blunting of the chronotropic response to exercise. With exercise, heart rate increases because of an increase in plasma catecholamines (released primarily from the adrenal glands) rather than from direct sympathetic stimulation of the sinus node. Thus, heart rate increase is delayed the heart rate peaks well after cessation of exertion and remains elevated until the circulating catecholamines can be metabolized (Fig. 8).

Glucocorticoids

Approximately 15-20 mg of cortisol is secreted daily. Corticotropin releasing hormone (CRF) from the hypothalamus is carried to the anterior pituitary gland in a portal venous system and stimulates release of ACTH. The ACTH circulates to the adrenal cortex where it stimulates synthesis and release of cortisol (very little cortisol is actually stored in the adrenal gland). Approximately 95 of glucocorticoid circulates bound to an a-globulin and the remainder is free steroid. A negative feedback effect from the free cortisol inhibits release of both CRF from the hypothalamus and ACTH from the anterior pituitary gland. There is a normal diurnal variation in glucocorticoid levels in 24 h with a trough at approximately 4 a.m. The main actions of glucocorticoids are

Adrenal medulla

Catecholamines are not essential for life but are essential for reaction to acute stress (preparation for 'flight or fight'). The sympathetic nervous system stimulates the adrenal medulla to release catecholamines directly into the circulation. In view of the anatomical position of the adrenal glands, this is directly into the upper inferior vena cava and directly to the heart for immediate effect. The main actions of catecholamines are

Healthy lifestyle

Obesity is associated with an increased risk of breast cancer in post-menopausal women, the mechanisms of which may be hormonal. It has been demonstrated that obese women metabolise androstenedione (from the adrenal gland) into oestrogen in the adipocytes. The circulating levels of oestrone are higher in obese post-menopausal women than non-obese individuals. In pre-menopausal women obesity may be associated with a reduced risk of breast cancer, although the reasons for this difference are unclear.

Gross anatomy

Anteriorly, the right kidney is covered on its medial aspect by the second part of the duodenum and the liver overlying the upper pole and hepatic flexure of the colon covering the lower part of the anterolateral aspect. The left kidney has the tail of the pancreas together with the edge of the greater curve of the stomach separated by the lesser sac on its medial aspect, the spleen lateral to this and the lower half of the kidney related to the splenic flexure of the colon. Both kidneys have the adrenal glands superomedially.

Pharmacokinetics

Studies of the distribution of 3H ginsenoside Rg1 following intravenous injection have been performed in mice (80). Tissue radioactivity was greatest in the kidney, followed by the adrenal gland, liver, lungs, spleen, pancreas, heart, testes, and brain. Plasma protein binding was 24 , and tissue protein binding was 48 in the liver, 22 in testes, and 8 in the brain.

Tumour

Adenocarcinoma of the kidney (also known as renal cell carcinoma) is the most common type of renal tumour. It can occur at any age, but is commonest in the sixth and seventh decade. About 60 of cases occur in men. Presenting symptoms can include haematuria, loin pain or a palpable mass. However, an increasing number of renal tumours are now diagnosed as incidental findings on CT or ultrasound scan, following investigation for other conditions (Fig. 19.6). Occasionally, a tumour will present with a paraneoplastic phenomena, such as thromboembolism, polycythaemia or anaemia. The primary tumour may metastasize directly to adjacent lymph nodes and the adrenal gland or distantly to the lungs and occasionally bone. Treatment of renal cell carcinoma depends on its stage, at presentation. If the tumour is confined to the kidney, radical nephrectomy (removing the kidney, perinephric fat and adrenal gland) is frequently curative. The operation can be

EiE2ATPases

Na K-ATPase is the receptor for the hormone ouabain, which is produced in the adrenal glands and involved in the regulation of blood pressure. The Na-gradient build by Na K-ATPase across the cell membrane is used to drive a Na Ca-exchanger, which reduces the cytosolic Ca-concentration. If Na K-ATPase is inhibited by ouabain, Ca transport out of the cell is reduced and the cytosolic Ca-concentration will increase. This will activate muscle contraction in the heart and in arterial walls, thus increasing pumped blood volume (inotropic effect) and blood pressure. Also, the hearts beating frequency is reduced.

Mortality

The initial spread of most germ cell tumors occurs to the lumbar para-aortic lymph nodes via the testic-ular lymphatics. Less frequently, direct lymphatic communication or hematogenous spread can occur, resulting in metastases to diverse areas. Two postmortem studies, one of 78 and the other of 154 patients with histologically confirmed germ cell tumors, found that metastatic disease often followed predictable patterns. In order of decreasing frequency, sites of metastases commonly reported were lungs (90 ), retroperitoneal lymph nodes (80 ), liver (70 ), mediastinal lymph nodes (65 ), brain (30 ), kidney (30 ), gastrointestinal tract (27 ), bone (20-30 ), adrenals (20-30 ), peritoneum (20 ), and spleen (10-20 ).1112 Less frequent sites of metastases include the pancreas, pleura, heart, pericardium, and vena cava.1112 The diaphragm, thyroid, breasts, eyes, skin, and spinal cord are rare reported locations for germ cell tumor spread.1112 Despite the great impact of platinum-containing...

Clinical Biology

The natural clinical history of prostate cancer is long, with projected transition from the first malignant cell in the prostate to distant metasta-tic disease taking more than 15 years in some cases and not occurring within the life span of a significant proportion of men.7 Important points at which the clinical course of the disease appears to accelerate include the development of metastases and the onset of resistance to primary hormone therapy. Local extension from primary prostate cancer may involve the bladder and seminal vesicles. This tumor also metastasizes through lymphatics to regional lymph nodes in the pelvis.8 Distant metastases commonly involve bone, especially the spine, but may involve distant lymph nodes and visceral organs, including the lung, liver, and adrenal glands.9

Glucocorticosteroids

Glucocorticosteroids have activity against prostate cancer. Their use as sole therapy is limited by long-term side effects including proximal myopathy, osteoporosis, and diabetes mellitus. While one study suggests they are as efficacious as flutamide in patients failing castration,140 in practice glucocorticosteroids are most often used as an adjunct to other therapy, such as aminoglutethimide or mitoxantrone. When used with aminoglutethimide, their primary role is to compensate for suppression of essential gluco-corticoid production by the adrenals.

HSD3B1 and HSD3B2

The enzyme 3 -hydroxysteroid dehydrogen-ase is a critical component of the androgen-me-tabolism pathway because it catalyzes andros-tendione production in steroidogenic tissues and converts active DHT into inactive metabolites in steroid target tissues. The HSD3B gene family has two genes and five pseudogenes, all of which map to chromosome 1p13.92-94 The HSD3B1 gene encodes the type I enzyme, which is exclusively expressed in the placenta and peripheral tissues, such as prostate, breast, and skin. The HSD3B2 gene encodes the type II enzyme, which is predominantly expressed in classical steroidogenic tissues, namely, the adrenals, testis, and ovary.93,95-98 A number of mutations in HSD3B2 have been found to cause congenital adrenal hyperplasia, a rare mendelian disease manifested by salt wasting and incomplete mas-culinization in males.99

And Growth Hormone

The anabolic effects of insulin are antagonized by glucagon, as previously described, and by the actions of a variety of other hormones. The hormones of the adrenals, thyroid, and anterior pituitary (specifically growth hormone) antagonize the action of As described in chapter 11, the adrenal gland consists of two parts that function as separate glands. The two parts secrete different hormones and are regulated by different control systems. The adrenal medulla secretes catecholamine hormones epinephrine and lesser amounts of norepinephrine in response to sympathetic nerve stimulation. The adrenal cortex secretes corticosteroid hormones. These are grouped into two functional categories mineralocorti-coids, such as aldosterone, which act on the kidneys to regulate Na+ and K+ balance (chapter 17), and glucocorticoids, such as hydrocortisone (cortisol), which participate in metabolic regulation.