Hormones are chemical messengers synthesized in the endocrine glands and secreted into extracellular body fluids. Hormones are transported to hormone-responsive cells, where they bind to a hormone receptor, and the hormone-receptor complex regulates and modulates differentiated functions. Hormones play critically important function in human health. Hormones and polypeptide growth factors are important regulatory substances that are involved in the regulation of cell growth and differentiation, as well as in the control of specific metabolic processes. The gonadotropin-releasing hormone (GnRH), also referred to as luteinizing hormone-releasing hormone (LHRH), is a decapeptide that plays a key role in human reproduction. The hormone is released from the hypothalamus and acts on the pituitary gland to stimulate the biosynthesis and secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Parathyroid hormone (PTH) is produced in the parathyroid, and plays an important role, acting on the bone and the kidney which are its target organs to control the blood calcium and phosphate ion levels. PTH and vitamin D are the principal regulators of calcium and phosphorus homeostasis. The metabolic actions of the hormone and vitamin D are interrelated.
Parathyroid hormone maintains extracellular fluid calcium concentration by increasing the rate of bone destruction with mobilization of calcium and phosphate from bone, increasing renal tubular resorption of calcium, increasing intestinal absorption of calcium and decreasing renal tubular resorption of phosphate. These actions account for all important clinical manifestations of parathyroid hormone excess or deficiency. Prolactin, also known as luteotropic hormone (LTH) or luteotropin, is a protein hormone produced by the pituitary gland of mammals and acts with other hormones to initiate secretion of milk by mammary glands. Adrenocorticotropic hormone (ACTH), also known as corticotropin, is a polypeptide hormone formed in the pituitary gland. ACTH is known to regulate the activity of the outer region (cortex) of the adrenal glands. Corticotropin stimulates secretion of glucocorticoids such as cortisol in humans (or corticosterone in rodents), and has little control over secretion of aldosterone, the other major steroid hormone from the adrenal cortex. ACTH binds to the MC-2R adrenocorticotropic hormone receptor expressed in the adrenal gland. The steroid glucocorticoid is produced by adrenal fasciculata-reticula cells in the adrenal glands, and is secreted in response to an increase in the level of plasma adrenocorticotropic hormone (ACTH). Glucocorticoids are involved in carbohydrate, protein, and fat metabolism, have been shown to have anti-inflammatory properties, and are hypersecreted during stress. Dopamine, also known as hydroxytyramine, is a nitrogen-containing, organic compound formed during the metabolism of the amino acid tyrosine. Dopamine functions as a neurotransmitter. The effects of the deficiency of dopamine is manifest in the form of Parkinson's disease.
Corticosteroids are steroid hormones related structurally to cholesterol. These hormones are synthesized in the adrenal cortex and include the glucocorticoids (e.g. corticosteroids), the mineralocorticoids (e.g aldosterone) as well as weak androgens and estrogens. The adrenal function, like that of the thyroid gland, is under the control of the hypothalamus (HPT) and the pituitary (PIT). When corticosteroids (the naturally-occurring glucocorticoid) levels drop below a setpoint, the hypothalamus releases CRH (corticotropin releasing hormone) which stimulates adrenocorticotropic hormone (ACTH) release from the pituitary. ACTH is a tropic hormone which stimulates the synthesis and secretion of corticosteroid (it has minimal effects on aldosterone synthesis/secretion), and the growth of the adrenal gland. Cortisol is the primary glucocorticoid produced by the adrenal cortex gland. The ACTH then circulates to the adrenal cortex where it stimulates the production and release of Cortisol. Once secreted into the general circulation Cortisol inhibits the release of CRH and also inhibits sensitivity to CRH thereby establishing a negative-feedback control over the system. The actual effect of Cortisol on an organism is to alter metabolic functioning and the body's immune response. Increased cortisol levels alter organic metabolism in a number of ways. It results in an increased mobilization of amino acids from protein stores in extra hepatic cells. It also results in an increase in transport of these amino acids to the liver. The liver converts these amino acids to glucose through a process called gluconeogenesis and uses the amino acids to increase production of plasma proteins. The increase in cortisol levels also serves to mobilize fatty acids from adipose tissues in an attempt to shift cells in the metabolic systems from the utilization of glucose for energy and to the utilization of fatty acids instead. In addition to its metabolic function, increased levels of cortisol serve to suppress the immune system. Cortisol is a steroid hormone that is released from the zona fasciculata of the adrenal cortex in response to stress. Some of the stressors that stimulate release of this glucocorticoid hormone include drastic changes in temperature, or heavy exercising. Cortisol is considered such a reliable indicator of stress upon a system that many physiologists define stress as an event that elicits increased levels of Cortisol. Glucocorticoid hormones play a critical role in a variety of bodily functions. Cortisol's ability to suppress the immune response may be exploited clinically to treat various inflammatory conditions such as allergies and arthritis. Cortisol may also be used in organ transplant operations to reduce the chance of organ rejection. Cortisol is essential for life; it helps an organism cope more efficiently in its environment. Cortisol is important in glucose and energy balance as well as moderating inflammatory response and immune mechanisms, in addition to many other functions. Cortisol is a critical hormone for controlling stress. In humans, cortisol is essential for life. Normally, cortisol secretion from the adrenal gland is rhythmic, with maximal blood levels in the early morning hours, and a decline to half of the peak value in the afternoon. During stress, excretion of cortisol is greatly increased to cope with serious whole body insult. However, sustained elevation of cortisol in circulation has detrimental effects on the immune system and on the ability of the body to cope with stress and disease. Pregnenolone is a steroid precursor produced in the human adrenal gland and in the human brain. Pregnenolone is produced in the desired amounts only if a person's body has adequate amounts of cholesterol, vitamin A, thyroid hormone, and enzymes. If these levels are insufficient, a low supply of pregnenolone will result. Of all steroidal hormones, pregnenolone has the greatest memory-enhancing effect, and can improve post-learning memory function at a dose 100 times lower than other memory-promoting steroids.
Androgens are another class of hormones. Androgens perform a wide range of beneficial functions throughout the body. Androgen refers to a family of male sex hormones which include, without limitation, dihydrotestosterone, androstenedione and testosterone. In the liver, they decrease the production of sex hormone-binding globulin and other hormone-binding globulins. Androgens serve to stimulate the proliferation of bone cells in vitro, a function that becomes increasingly beneficial with age, as peak bone mass in men is in their mid-twenty's and linearly declines with age after that point. Androgens such as testosterone, play a key role in the development of male sexual characteristics such as growth of the penis, muscles and beard as well as deepening of the voice. Testosterone secreted by the Leydig cells was also known to bind to specific receptors in the Sertoli cells and this binding was known to be important in sperm production. Androgens are the hormones of choice in helping restore lost sex drive, although estrogens alone may help some women. Several reports in the literature establish the beneficial effects of androgen therapy on sexual function. Testosterone is quantitatively and qualitatively the most important androgen synthesized in the body. It is formed mainly in the testicles and in small amounts in the adrenal glands and in women in the ovaries. Testosterone's effects include maintenance of muscle and bone mass, improving and/or enhancing sexual function and psychological well being among others. As males grow older, especially after the age of 35, a slow decline in testosterone levels is observed which is accompanied by symptoms that have been associated with the condition known as "andropause". Symptoms of andropause include lethargy, depression, lack of sexual desire and function, and loss of muscle mass and strength. Increasing testosterone levels therefore can be useful to treat any of the mentioned conditions. In males, testosterone is responsible for the development of the male characteristics during fetal, neonatal and pubertal maturation and finally for attaining the male phenotype and for androgen-dependent functions. Testosterone has been shown to lower cholesterol and normalize the abnormal electrocardiograms of patients. Testosterone can also improve diabetic retinopathy as well as lower the insulin requirements of diabetic patients and decrease the percentage of body fat. Administration of testosterone to men has been reported to decrease risk factors for heart attack and low testosterone is also correlated with hypertension, obesity, and increased waist-to-hip ratio. The hematologic and immunologic effects of androgens include the stimulation of the production of erythropoietin in the kidneys, which increases hemoglobin concentrations. A weak androgen known as danazol is used to treat endometriosis in women due to its direct antiprogestational effects on the endometrium. Testosterone treatment may help to decrease the symptoms of autoimmune disease. Additionally, increasing testosterone levels can be useful in treating certain types of breast cancer in women. Androstenedione is an adrenal steroid hormone. Pregnenolone is a precursor for dehydroepiandrosterone. Dehydroepiandrosterone (DHEA) is a precursor of androstenedione. Androstenedione is a direct precursor of estrone and testosterone in target tissues that possess the appropriate receptors and enzymes. Androstenediols are direct precursors for testosterone after oral administration in adult humans. 19-Norandrostenedione is a precursor for 19-nortestosterone, which has anabolic actions similar to testosterone, with less androgenic actions.
All hormones are found in both men and women. Each sex has more of some and less of others. The female hormones, estrogen and progesterone, are known to drop drastically to very low levels after menopause. Menopause is a biological process in which a woman's ovaries reduce but do not completely stop their production of female sex hormones. Menopause is diagnosed when menstruation ceases permanently. During a woman's reproductive life, a delicate and complex interplay of hormones are timed and controlled by the hypothalamus. The hormones that participate in the feedback system regulating the menstrual cycle include estrogens and progesterone, the pituitary gonadotropins FSH (follicle stimulating hormone) and LH (luteinizing hormone), and gonadotropin-releasing hormone (GnRH) from the hypothalamus. Progesterone is a naturally occurring progestin-type hormonal steroid. It has certain unique properties and provides unique pharmacological activities when administered. Progesterone provides certain advantages based on being a naturally occurring compound. Progesterone is useful to alleviate postmenopausal symptoms. Administration of combinations of progesterone or a synthetic progestin and an estrogen can be useful either as a contraceptive or as a hormone replacement. Progesterone may help with emotional and psychological symptoms, libido, headache, rhinitis, sore throat, sinusitis, skin dryness, alopecia (thinning hair), glaucoma, and auto-immune disorders. It may improve a lipid profile, cause new bone formation, decrease risk of coronary vasospasms, and is often effective for pre-menstrual syndrome. Women who have progesterone deficiency may show signs such as weight gain, hot flashes, sleeplessness, hypothyroidism, yeast infections, and fibrocystic breasts. Estrogen is primarily a female sex hormone, and is responsible for the growth of female sexual characteristics and female reproductive functions. Estrogen is made in the ovaries as well as fat cells, muscle cells and skin. Estrogen deficiency symptoms include vaginal dryness, problems with memory, hot flashes, night sweats, depression, lethargy, and fatigue. Estrogen is produced before and after menopause. Estrogens play a major role in hormonal contraception, in menopausal hormone replacement therapy (HRT), and for treating gynaecological diseases and andrologic diseases (e.g. prostatic carcinoma). For HRT and contraception, estrogens are mainly used together with a gestagen, e.g. levonorgestrel, desogestrel, norethisterone, cyproterone acetate, chlormadinone acetate, dienogest. Estradiol is the main estrogen secreted by the female gonad during the fertile years of life. Estradiol is a potent mammalian estrogenic hormone produced by the ovary. It triggers the production of gonadrotropins leading to ovulation. Estradiol is a female sex hormone that stimulates the appearance of secondary female sex characteristics in girls at puberty. Estradiol controls growth of the lining of the uterus during the first part of the menstrual cycle, cause changes in the breast during pregnancy, and regulate various metabolic processes. Increasing estradiol can treat various conditions, including menopausal symptoms, estrogen deficiencies in women and inflammation of the vagina. Estradiol has been isolated from the follicular fluid of sow ovaries, and from the urine of pregnant women and mares. It makes up 10%-20% of the estrogen in younger women. Estradiol is thought to be important to protect cardiovascular and cognitive function. Natural estrogens (estradiol, estrone, estrone sulfate, esters of estradiol, estriol) are bio-available to only a very small extent when administered orally. The estrogen dose in the HRT must very often be matched individually. The quick elimination of substances from the blood is also problematical in nature.
Melatonin is another hormone that decreases substantially with advancing age. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone synthesized and secreted principally in the pineal gland. Melatonin reaches its peak levels before the onset of the cortisol peak in humans. The production of melatonin declines with age. Melatonin is a natural hormone which is synthesized by the body and exists in every cell. It is derived from serotonin, a neurotransmitter which in turn is converted from an amino acid by the pineal gland. Age adversely affects the ability to synthesize melatonin and this decline is believed to play a prominent role in the aging process. Melatonin is involved in the coordination of photoperiod and physiological processes, e.g. in animals which use changes in the photoperiod to time their thermoregulation and reproduction, temporal signals to the thermoregulatory and reproductive systems are controlled by the daily rhythm in the duration of melatonin during the dark phase. Numerous studies have shown that melatonin has a potent influence on gonadal activity. Melatonin exerts suppressively on pigment cells or female gonad and acts as a synchronous factor of biological clock while taking part in transmittance of photoperiodic code. Therefore, melatonin is considered to be possibly used for the therapy of diseases related with melatonin activity, such as reproduction and endocrinic disorders, sleep-awake rythm disorders, jet lag syndrome and various disorders related to ageing. Melatonin exhibits strong antioxidant properties, particularly with regard to peroxyl and hydroxyl radicals, and there is evidence that it is also a potent inhibitor of nitric oxide. Nitric oxide is believed to play an important role in the stimulation of free radical damage. Melatonin protects cells by stimulating glutathione peroxidase which converts reduced glutathione to its oxidized state, thus inhibiting the production of hydroxyl radicals. Studies have shown that melatonin is a more powerful antioxidant than vitamins E and C as acting as a "free-radical scavenger" and for protection against aging. Melatonin is also more efficient than vitamin E as a scavenger of the peroxyl radical, which contributes to massive lipid destruction in cell membranes. Melatonin also protects against a variety of degenerative and age-related neurological conditions of the brain, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and depression. Melatonin has also been shown to prevent cataracts. Melatonin has been used by itself and as adjuvant treatment for cancer, heart disease, stroke and Alzheimer's disease with some successes. Melatonin has also been studied for its antioxidant activity and for formulation into dermocosmetics for improving the appearance of the skin or for protecting the skin against the deleterious effects of irradiation with UV rays.
The hormone dehydroepiandrosterone (DHEA) is produced from cholesterol in the adrenal glands and serves a wide variety of functions, providing health and longevity benefits. It is a hormone that the body converts on demand into such hormones as estrogen, progesterone, testosterone, and androstenedione. Dehydroepiandrosterone (DHEA) and its sulfated form, dehydroepiandrosterone-sulfate (DHEAS) are the principal circulating steroids in humans. These two steroids are synthesized in the adrenal cortex. DHEAS is thought to be the storage form of DHEA, and can be converted to DHEA by the action of a sulfatase. DHEA can serve as a substrate for the production of androgenic steroids, both in the steroidogenic organs (adrenal glands, gonads and placenta) and in peripheral tissues, such as the skin, liver and brain. DHEA is weakly active as a sex hormone but is a precursor within the body for the androgen testosterone in the male and for estrogenic hormones such as estrone and estradiol in the female. DHEA is rapidly sulphated to DHEA sulphate before release into the circulation and it is this latter species which constitutes the main circulating form of the steroid. DHEA is synthesized from pregnenolone in a two step reaction by cytochrome P450c17 (CYP17). Insulin-like growth factor I (IGF-I) has been reported to increase transcription of the CYP17 gene in cultured Leydig cells, although expression of the 313-hydroxysteroid dehydrogenase gene (which encodes an enzyme involved in the conversion of DHEA into androgenic steroids and 17-alpha-hydroxypregnenolone into cortisol) was not affected. Insulin-like growth factor I (IGF-I) also increases choriogonadotropin-stimulated production of testosterone by Leydig cells. DHEA and DHEAS levels normally peak in the second or third decade of life, declining by 80% or more of peak levels by age 70. Low levels of DHEA and DHEAS are associated with a variety of disease conditions, including Alzheimer's Disease and cardiovascular disease. DHEA and its derivatives have been described as treatments for a wide variety of conditions, including memory dysfunction, prostatic hypertrophy, immune dysfunction, alopecia, for inhibiting platelet aggregation, and minor and major depression as well preventatives for cancer and cardiovascular disease. Direct administration of DHEA, DHEAS and their derivatives can lead to serious side effects. For example, acne, hair loss, hirsutism and deepening of the voice have been reported with use of DHEA in women. Excess DHEA may stimulate the growth of prostatic cancer in men. A natual metabolite of DHEA is 7-keto dehydroepiandosterone (7-keto DHEA), also known chemically as 3-beta-acetoxyandrost-5-en-7,17-dione. 7-keto DHEA has therapeutic applications in immune modulation, immune enhancement through T-cell upregulation, memory enhancement, and weight loss and management by means of its theromagenic-enhancing action.
Human growth hormone (hGH), also known as somatotropin, is a protein hormone produced and secreted by the somatotropic cells of the anterior pituitary. Human growth hormone plays a key role in somatic growth through its effects on the metabolism of proteins, carbohydrates and lipids. In addition to its effects on somatic growth, hGH has been shown to stimulate hematopoiesis (proliferation, maturation and function of erythroid, mycloid and lymphoid lineages). In its mature form it consists of 191 amino acids, has a molecular weight of 22,000 and thus is more than three times as large as insulin. This hormone is a linear polypeptide containing two intrachain disulfide bridges. The major biological effect of hGH is to promote growth. The organ systems affected include the skeleton, connective tissue, muscles and viscera such as liver, intestine and kidneys. Growth hormone exerts its action through interaction with specific receptors on cell membranes. Growth hormones affect the metabolic processes of the body by increasing the rate of cellular protein synthesis and decreasing protein degradation, as well as by increasing the rate of use of fatty acids and decreasing the rate of use of carbohydrates for production of energy in the body. Human growth hormone is the most abundant hormone produced by the anterior pituitary lobe, accounting for as much as eight to ten percent of the dry weight of the gland. The physiological effects of human growth hormone are macroscopic, extending beyond cellular, chemically mediated events. One example of this is the effect of human growth hormone on whole body growth. GH as well as thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and the like are under the control of the hypothalamus. It has been found that secretion of each pituitary hormone is specifically stimulated by the corresponding releasing hormone (RH) secreted from hypothalamus. Growth hormone releasing hormone factor is a peptide of 44 amino acids. There are analogs containing 27-40 amino acids. It is one of a group of peptides secreted by the hypothalamus, and it normally stimulates pituitary growth hormone release. It is important in normal growth and development during childhood. The hypothalamus regulates many of the functions of the anterior pituitary by secreting a corresponding hypothalamic releasing factor which stimulates the secretion of the anterior pituitary homones. Recombinant human proteins have become important pharmaceuticals. The combination of recombinant DNA technology and large-scale processes has enabled production of proteins that might otherwise have been impossible or too expensive to obtain from natural sources.
Hormone intake by humans can occur through consumption of pharmaceutical compositions, foodstuffs, nutritional supplements and nutraceuticals. Such hormones include phytoestrogens, or nonsteroidal estrogens, steroidal estrogens and progestins. Phytoestrogens comprise, for example, genistein, daidzein and glycitein, and their respective glucoside, malonylglucoside and acetylglucoside derivatives. Estrogens and progestins are known to be used for hormone replacement therapy (HRT) and in contraceptive medications. Estrogens play a major role in hormonal contraception, in menopausal hormone replacement therapy (HRT), and for treating gynaecological diseases (e.g. mammary carcinoma) and andrologic diseases (e.g. prostatic carcinoma). It is now well known that hormone replacement therapy (HRT), such as estrogen treatment, improves or reverses the adverse effects of the decrease in sex steroid secretion by the ovaries during menopause in women. For HRT and contraception, estrogens are mainly used together with a gestagen, e.g. levonorgestrel, desogestrel, norethisterone, cyproterone acetate, chlormadinone acetate, dienogest. Estrogens have also been shown to improve mood and psychological well-being in postmenopausal women and they also prevent atrophic changes in the genital tract. Estrogens have been shown to effect arterial tone and this may help to explain the reduction in hot flushes observed in postmenopausal women with estrogen therapy. Natural products with anti-estrogen activity include catechin polyphenols, tocotrienols, isoflavones and similar flavonoid compounds such as citrus flavonoids and saponin flavones, phytosterols, resorcyclic acid lactones, indoles, saponins, glucarates and guaianolides from Asteraceae species. Substances with anti-DHT-activity include zinc salts, Saw Palmetto berry (Serenoa repens), Pygeum africanum, and green tea (Camellia sinensis). Natural products with anti-estrogen activity and substances with anti-DHT activity may further include whole herbs or plants, parts thereof, powders thereof, and semi-purified extracts as well as purified extracts.
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