Hormones are your body's chemical messengers that travel in your bloodstream to tissues or organs. They control important bodily functions and affect many different processes, including:
Growth and development
Endocrine glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, thymus, thyroid, adrenal glands, and pancreas. In addition, men produce hormones in their testes and women produce them in their ovaries.
Hormones are powerful. It takes only a tiny amount to cause big changes in cells or even your whole body. That is why too much or too little of a certain hormone can be serious.
The endocrine system provides an electrochemical connection from the hypothalamus of the brain to all the organs that control body metabolism, growth and development, and reproduction. Endocrine Glands are those glands which have no duct and release their secretions directly into the intercellular fluid or into the blood. The collection of endocrine glands makes up the endocrine system.
The endocrine and nervous systems often work toward the same goal. Both influence other cells with chemicals (hormones and neurotransmitters). However, they attain their goals differently. Neurotransmitters act immediately (within milliseconds) on adjacent muscle, gland, or other nerve cells, and their effect is short-lived. In contrast, hormones take longer to produce their intended effect (seconds to days), may affect any cell, nearby or distant, and produce effects that last as long as they remain in the blood, which could be up to several hours.
The following figure shows major hormonal organs (fig 1). Hypothalamus secretes hormones that regulate the function of the anterior pituitary gland.
The pituitary gland produces:
-Thyroid stimulating hormone (TSH)
- Adrenocorticotropic hormone (ACTH) that stimulate the adrenal cortex
- Gonadotropic hormones that regulate egg and sperm production, and sex hormones production
- Prolactin that regulates milk production during breastfeeding
- The growth hormone regulates cell division. protein syntheses and bone growth
One out of 10 people suffers from thyroid dysfunction, half of which go undiagnosed. Most People with hypothyroidism can take thyroid hormone medication but still suffer from fatigue, weight gain, depression, constipation, dry skin, hair falls, cold hands and feet…..
The most common cause of hypothyroidism in the United State is an autoimmune disorder called Hashimoto’s disease, in which the immune system attacks and destroys thyroid gland tissue. Except that, there are many different patterns of low thyroid function, only one of which can be resolved with thyroid medication. Hypothyroidism involves not only the gland itself but other organs and systems. Low thyroid affects bone metabolism, fat burning, high cholesterol and male reproduction (Fig.2).
Figure 1. Major organs that produce hormons
Figure 2. Some of the functions that depend on activity of thyroid. Low hormonal level depresses function of other organs
The thyroid is very sensitive to the slightest alterations in the body and, in turn, impact to other body systems. It looks like a vicious cycle. Irregular immune function, brain chemistry, poor blood sugar metabolism, gastrointestinal disorders, liver and gallbladder function, adrenal problems, anemia, hormonal imbalances significantly depress thyroid function. It looks like alteration in thyroid function depletes body systems and organs.
The brain secretes thyroid releasing hormone (TRH) and thyroid-stimulating hormone (TSH), which regulate secretion the thyroid hormones T4 (thyroxine) and T3 (triiodothyronine). The thyroid produces 93% of T4 and 7% of T3. The body converts T4 into T3 which is used by cells nuclei and switch on or off genetic control. The thyroid hormones are tyrosine-based hormones that are primarily responsible for the regulation of metabolism. Iodine is necessary for the production of T3 and T4. A deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as goiter. The major form of thyroid hormone in the blood is T4, which has a longer half-life than T3; T4 is converted to the active T3 (three to four times more potent than T4) within cells by deiodinases that are selenium-containing enzymes. Thus, dietary selenium is essential for T3 production. Hypothyroidism is the condition that results from under-production of thyroxin by the thyroid gland either because the gland is naturally underactive or because radioiodine therapy or surgery for an overactive gland has resulted in underactivity.
Most conversions of T4 into T3 happened in the liver (60%). This conversion depends on liver health. The intestines convert about 20% of T4 into T3 but only in the healthy gut and presence of enough healthy intestinal microflora. Thus, the health of many body systems depend on health of liver and gastrointestinal tract (fig.4).
Figure 3. Impact of adrenal imbalance,
leaky gut and blood sugar fluctuation on thyroid function
A tight relationship exists between thyroid and adrenals. Chronic adrenal stress affects communication between the brain and the hormonal glands, suppressing hypothalamus and pituitary gland hormone production and disrupt thyroid hormones metabolism; hampers the conversion of T4 to T3; decreases the sensitivity of cells to thyroid hormones (fig.3). Low thyroid function is almost always secondary to adrenal stress, low or high blood sugar, leaky gut.
Figure 4. Pathway of thyroid hormones metabolism
The adrenal glands are two glands that sit on top of your kidneys and are made up of two distinct parts: cortex and medulla (fig.5).
The adrenal cortex produces cortisol (which helps regulate metabolism and helps your body respond to stress) and aldosterone (which helps control blood pressure).
The adrenal medulla—the inner part of the gland—produces adrenaline (epinephrine), which helps your body react to stress.
Figure 5. Adrenal glands and hormones produced by the adrenal cortex and medula
The medulla and cortex are functionally different endocrine organs and have different embryological origins.
Epinephrine and Norepinephrine are synthesized from amino acid tyrosine. Both hormones have the same effect as sympathetic nerves. Epinephrine and norepinephrine are the flight/fight hormones that are released when the body is under extreme stress. Both hormones increase the rate and force of contraction of the heart increasing the blood pressure. The hormones also have important metabolic actions. Epinephrine stimulates the breakdown of glycogen to glucose in the liver, which results in the raising of the level of blood sugar. Both hormones increase the level of circulating free fatty acids.
The cortex produces glucocorticoids (cortisol), mineralocorticoids (aldosterone) and androgens (estrogens, testosterone, progesterone). All steroid hormones are synthesized from cholesterol (fig 6). Steroidogenesis is largely confined to the adrenal cortex, testicular cells, and ovarian cells. Steroidogenic cells can employ four potential sources of cholesterol for steroidogenesis:
synthesized by adrenal cortex itself;
cholesterol stored in lipid droplets;
uptake of circulating HDL;
uptake of LDL.
The cortex is under control of the brain, the medulla is under control of the nervous system.
Figure 6. Major pathways of steroid biosynthesis
Cortisol is a life sustaining adrenal hormone essential to the maintenance of homeostasis. Cortisone is the inactive steroid related to cortisol and the reversible interconversion of cortisone into cortisol. The conversion of cortisone to cortisol depends on the activity of enzymes produced in the liver and kidney. Cortisol is often referred to as the "stress hormone" as it is involved in the response to stress. This glucocorticoid shuttle also helps to initiate and regulate the anti-inflammatory response. Cortisol levels normally fluctuate throughout the day and night. It should be higher in the morning that makes you feel awake and energetic in the morning and ready for bed in the evening (Fig. 7).
Figure 7. Levels of cortisol from morning to midnight
If cortisol level is low in the morning people wake up tired and sleepy. A high level of cortisol in the evening makes people staying asleep or don’t sleep deeply. Cortisol is highly affects thyroid health, GI tract health, blood pressure, blood sugar levels, and other actions of stress adaptation.
The adrenal glands are key to our energy level and our immune responses. Things that create the adrenal exhaustion are stress, infections, particularly respiratory infections, inappropriate foods, lack of sleep. People can be born with tired adrenal glands (mostly if the mother had a stressful pregnancy). In post-menopause women (when the ovaries are shutting off), the adrenal glands begin producing androgens which are converted to estrogen.
Up to 80% of all adults suffer from some level of adrenal fatigue at some time. Dark circles under the eyes or the puffy bags under the eyes are a real indication of weak adrenals. The puffiness is a little more kidney related. Since the adrenals have a big influence on the fluid balance on the body, the puffiness can mean that the adrenals were the first to buckle.
TESTES AND TESTOSTERON
Testosterone (TS) in steroid hormone produces by testes. It maintains the primary and secondary sex characteristics in men. Its metabolites include estradiol and dihydrotestosteron, which is an androgenic hormone that is approximately three to ten times more potent than TS. In recent years there has been an explosive increase in prescriptions for TS replacement therapy in adult men thought to have adult androgen deficiency (AD).
Figure 8. Effects of testosterone on men
The TS levels in men beginning at about 40 years old, decrease with age, at approximately, one percent per year.
There is a debate about whether or not to interpret lower TS values in older men as being physiologic or abnormal. In younger men there is marked diurnal variation in TS levels, highest levels occur in the early morning upon awakening. In older men the diurnal variations are less pronounced. Nevertheless, the blood sample for total TS recommended being drawn before 10 am in all men. Total TS levels can vary considerably from day to day in the same man.
Factors that can change the total TS variation include sleep, diet, stress, illness, and exercise. Low TS affects many of the body organs and tissues (fig. 8). Consequently, it is not advisable to make a diagnosis of low TS on the basis of a single blood test result. Instead, two or even three tests taken on different days are recommended in order to ensure an accurate diagnosis.
Based on recommendations from various sources, it appears that the clinical threshold for diagnosing low TS probably lies somewhere between 300-500 ng/dL. The American Urological Association states that there is no universally accepted threshold of TS concentration. The Endocrine Society recommends making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and low serum TS level.
Many experts now recommend that numerical values for total testosterone should be interpreted only in the context of the other clinical features of the patient. Although all of these signs and symptoms are somewhat nonspecific, the sexual symptoms appear to be the most useful indicators particularly for men older than 45 years of age. The levels of total testosterone in men decline gradually with age.
Other conditions besides aging also contribute to significant declines in testosterone in men older than 45 years of age. Chronic opioid use and obesity are two of the most significant drivers of reduced total testosterone. AIDS, hypertension, overtraining, certain medications, and diabetes are also associated with low TS. There is convincing evidence that poor sleep quality and insufficient sleep can cause and decrease TS level.
Two types of biochemical compounds with hormonal activity are synthesized and secreted by ovarian tissue. One has a steroidal structure which includes androgens, estrogens, and progestogens. The second is a polypeptide hormone relaxin.
The effects of relaxin are most well-described during the female reproductive cycle and pregnancy. During pregnancy, relaxin levels are at their highest in the first trimester, promoting implantation of the developing fetus into the wall of the uterus and the growth of the placenta. Early in pregnancy, relaxin also inhibits contractions in the wall of the uterus, to prevent premature childbirth. Relaxin belongs to the same family of hormones as insulin. Elevated concentrations of maternal relaxin during pregnancy are associated with preterm birth, the lack of relaxin is associated with increased insulin resistance.
The three major estrogens in women are estradiol, estriol, and estrone (fig 9).
Estrogen is synthesized from testosterone by the enzyme aromatase.
Estradiol is the predominant estrogen during reproductive years. Estrogens are primarily responsible for the conversion of girls into sexually-mature women. Estradiol production is most commonly thought of as an endocrine product of the ovary; however, estrogens also have non-reproductive effects. There are many tissues that have the capacity to synthesize estrogens, such as the adipose tissue, the breast, osteoblasts, and chondrocytes of bone, the vascular endothelium and aortic smooth muscle cells, and numerous sites in the brain can contribute significantly to the circulating pool of estrogens.
Thus, the estrogen which is responsible for breast cancer development, for the maintenance of bone mineralization and for the maintenance of cognitive function is not circulating estrogen but rather that which is produced locally at these specific sites within the breast, bone, and brain.
Postmenopausal osteoporosis is believed to be related to the low estrogen levels. They antagonize the effects of the parathyroid hormone minimizing the loss of calcium from bones and thus helping to keep bones strong. Estrogens also promote blood clotting.
Estrogen plays a role in cell activity. When estrogen is released, it passes directly into cells throughout the body, binds to receptors in the target cells, and initiates cell activity. Estrogens role in signaling cells to divide and multiply can trigger and promote abnormal growth of estrogen-responsive tissues. Treatment of these disorders, therefore, involves blocking the action of estrogen of the affected tissues mostly through aromatase inhibition.
Estrogen dominance leads to estrogen toxicity that reduces the number of stem cells. Examples of the estrogen-dominant disorder are endometriosis, cysts, and fibroids, menstrual disturbances.
Many plants produce the estrogen-like phytoestrogens that mimic estrogen and interact with hormone signals. Exposure to phytoestrogens is mainly through diet. The estrogenic plant compounds are widespread in food, including herbs and seasonings (garlic, parsley), grains (soybeans, wheat, rice), vegetables (beans, carrots, potatoes), fruits (date, pomegranates, cherries, apples), and drinks (coffee). The two most studied phytoestrogen groups are lignans and isoflavones. Lignans are products of intestinal microbial breakdown of compounds found in whole grains, fibers, flax seeds, and many fruits and vegetables. Isoflavones, such as genistein and daidzein, occur in soybeans and other legumes.
Figure 9. Three forms of estrogens
Exposure to environmental estrogens has been proposed as a risk factor for the disruption of reproductive development and tumorigenesis of humans. It includes many conditions: breast, prostate and testicular cancer, obesity, infertility, endometriosis, early onset puberty, miscarriages, and diabetes. This kind of estrogens can bind to the estrogen (and androgen) receptors and mimic the effects of the hormone. There may be synergistic effects with xenoestrogens (pesticides, herbicides, plastics, refrigerants, industrial solvents, bleach byproducts, the hormones used to fatten livestock and promote milk production, found in factory-farmed meat and milk products).
Strategies for reducing estrogen toxicity include:
prevent high estrogen production with natural aromatase and flavones;
clog up the estrogen receptors with lignans and phytoestrogens;
improve estrogen break down to healthy metabolites with exercise, cruciferous vegetables;
remove xenoestrogens through detoxification.
A healthy lifestyle, exercise, and diet will help to avoid estrogen toxicity.