Meet your hormones: the endocrine system
Hormones are a dually intricate matter: they are complex in and of themselves, and bioindividually elusive. While we each have a unique hormonal make-up determined by genetics, epigenetic mechanisms influenced by diet, lifestyle and the ups and downs of life in general, play a big role in how our hormones perform and interact. Hence, delving into hormonal imbalances may often feel like going down a rabbit hole, since these bustling little biomolecules change, transform, fluctuate and often behave erratically, in response to myriads of internal and external stimuli. So much so that allopathic medicine professionals are too often baffled by the endless nuances of hormone imbalances, and blood tests simply cannot provide full disclosure of hormonal inefficiencies. Sadly, because the process of restoring hormonal harmony is lengthy and it usually requires a multi-pronged approach, many of us tend to resignedly come to accept chemical rollercoasters manifesting as fatigue, depression, anxiety, hair loss, weight gain, lack of sex drive, etc. as the norm, and raise a white flag. To make matters worse, mainstream medicine is quick in prescribing replacement hormones (lab-made copies), when one of them is off the charts, with undesired and potentially catastrophic fallouts. Conventional testing for some hormones (estrogens and thyroid hormones, for instance) can be utterly misleading, and accurate functional testing is still not covered by medical insurance. This is the reason why many doctors offer dismissive idiopathic diagnoses when faced with unexplained symptoms and associated markers, attributing them to normal age progression or genetics.
Before tackling hormonal issues as they relate to and trigger metabolic dysfunctions and other health conditions, I decided to help clear up some of the confusion about where the most important hormones come from, what they do and why we need them. This will serve later as reference, as I investigate ways to naturally support our own hormones in carrying out their functions as smoothly and harmoniously as possible. There is no reason to feel unwell and do nothing about it, just because we are told to accept it as normal.
Hormones are biomolecules (substances produced by living organisms that are essential for life) that are continuously produced internally by a network of little factories called endocrine glands, but also from scattered cells in other tissues located throughout the entire human body, like the digestive system, the heart, the kidneys and adipose cells. These biomolecules convey messages via the bloodstream to, from and between systems in the body; they travel around instructing nearby and distant organs and systems as to how to behave and what to do under variable internal and external circumstances. For the purpose of this article, I will focus exclusively on the glandular signaling system.
The Endocrine System
The word ‘endocrine’ comes from the ancient Greek ἐνδο (endo), meaning ‘internal’, and κρινις (krinis), which means ‘to secrete’, denoting glands having an internal secretion. While the endocrine system produces hormones, it needs sparks by the nervous system to initiate and sustain hormone production and activity, which means these two systems are electrically/chemically interrelated. Endocrine glands and tissues do not work alone: each action on the part of one of them triggers and determines actions by the next, and the reverse happens through a rolling feedback mechanism. Following is a list of the endocrine glands with a description of their primary functions and lists of hormones they produce. Future articles exploring weight loss, emotional health and aging solutions will look at these hormones in more details and explore their behaviors and interactions.
For quick reference, structurally, hormones can be classified as follows:
1. Steroids, or cholesterol based. Their signals linger in the body for an extended time until the hormones are broken down to be excreted by way of urine or feces.
2. Peptides, peptide chain or protein based hormones. They have a short circulating plasma half-life, meaning they are eliminated rather quickly after they perform their tasks. This makes these chemicals perfect for quick intracellular communications.
3. Amines, tyrosine and tryptophan amino acid based.
4. Glycoproteins, made from peptides and carbohydrates.
Additional classifications include:
1. Neurohormones, chemicals that originate from nervous system cells, released into the bloodstream, synthesized in and released by the endocrine glands.
2. Neurotransmitters, chemical messengers that transmit nerve impulses across synapses, among neurons or from neurons to muscles.
Hypothalamus
This almond-sized gland is located at the base of the forebrain (the frontal part of the brain). The hypothalamus contains a number of neuronal nuclei, or clusters of neurons that share similar functions, and therefore plays a role in the limbic system, an aggregate of brain structures that regulate emotional reactions, behavioral responses, memory processes and olfactory sense.
The hypothalamus has a unique role in that it belongs to the nervous system as much as the endocrine system, acting as a connector and coordinator between the two. Its primary function is maintaining homeostasis in the body [homeostasis is the natural tendency of the human body to return to a state of equilibrium in chemical, physical and emotional terms], which it carries out by way of neuronal pathways and endocrine activity - meaning it sends out stimulating electrical and chemical signals to all other systems via the neighboring pituitary gland. Here is a summary of the functions the hypothalamus controls:
Autonomic function: (think heartbeat, blood flow and digestion) and motor function control (voluntary movements).
Food and water intake regulation: the brain receives signals from the gastrointestinal tract through sensory nerves and via the circulation. The neurons involved in homeostatic regulation of feeding are in fact located mainly in the hypothalamus and in the brainstem (the stalk shaped portion of the brain that connects it to the spinal cord). These feedback receptors sense glucose metabolism, body fat reserves (which the hypothalamus is evolutionarily programmed to create) and distension of the stomach, as well as the concentration of sodium, blood volume and pressure: the hypothalamus has the ability to calibrate all of these functions by triggering hunger and thirst through neuropeptides, as needed.
Sleep/wake cycle and hormonal rhythmicity: this function is of critical importance to human health. In the hypothalamus, a cluster of neurons called the suprachiasmatic nuclei (SCN) receives photic input from the retina via the optic nerve and responds to environmental prompts such as food availability and social cues, regulating the circadian rhythm, a process that scans our 24hr sleep/wake cycle, synchronizing biological processes throughout the body accordingly. Hormones exhibit circadian (24hr), ultradian (less than 24hrs but more than 1hr) and circannual (yearly) rhythmicity, controlled by this internal clock which also allows for anticipation of seasonal changes. Disruptions in hormone rhythmicity have been associated with metabolic dysfunctions and the onset of chronic disease.
Body temperature regulation: the hypothalamus strives to maintain our body temperature within one or two degrees of 98.6F by triggering sweat and chills. This happens in response to a heat/cold feedback system that involves the skin, blood vessels and sweat glands, and in response to external changes.
Stress response and immune adaptation: by working in assiduous collaboration with pituitary and adrenal glands (the HPA axis), the hypothalamus modulates our response to stressful situations and to pathogens and chronic illness.
Sexual and social behavior regulation: the hypothalamic region of the brain releases neurohormones that inform our behaviors with relation to family, friends and partners.
Reproductive system information: the hypothalamus, upon feedback from other endocrine glands, decides whether or not a pregnancy is sustainable under certain internal circumstances such as low thyroid function or low progesterone (particularly during times of stress or grief), and informs the reproductive system accordingly. This is an evolutionary mechanism meant to avoid miscarriages or giving birth to offspring with defects.
Hormones released by the hypothalamus:
MSH, Melanocyte-stimulating hormone regulates: sleep, UV light protection, appetite suppression, salt/water balance, learning/memory, inflammation, sexual arousal and nerve regeneration by stimulating melanin production in the skin.
CRH, Corticotropic-releasing hormone provides stress response regulation by nudging the adrenals to produce cortisol.
TRH, Thyrotropin-releasing hormone regulates thyroid function via the pituitary, by inducing it to produce Thyroid Stimulating Hormone, hence controlling metabolism and energy through thyroid hormonal output.
GHRH, Growth hormone-releasing hormone urges the pituitary to make Growth Hormone; GHRH indirectly regulates: growth spurts; body fluids; muscle and bone cell growth; sugar and fat metabolism.
GnRH, Gonadotropic-releasing hormone instructs the pituitary to secrete FSH, Follicle Stimulating Hormone and LH, Luteinizing Hormone, which in turn regulate growth, sexual developments and reproduction by acting on ovaries and testes so they produce sex hormones.
PRH, Prolactin-releasing hormone induces prolactin production in the pituitary, immune cells, skin, prostate, breast and uterus tissues. Prolactin controls: lactation; sleep; metabolism; mental health; reproduction; immunity.
ADH, Anti-diuretic hormone or Vasopressin raises blood pressure by suppressing kidney urine production and enhancing conservation of body fluids.
Somatostatin, which is also a releasing hormone, secreted in the gut and pancreatic tissues as well, inhibits production of other hormones such as: growth hormone, also conversely called somatotropin; cortisol; prolactin; TSH; glucagon and insulin; gastric CCK. It balances digestion, metabolism, growth and several other functions through its inhibitory actions.
Oxytocin is a neuropeptide known as the love hormone. It is sent to the pituitary, where it is stored and then released; it promotes social bonding, love, affection and sexual intercourse. It also stimulates breast milk production and uterine contractions during gestation.
Neurotransmitters released by the hypothalamus:
Dopamine is our reward and pleasure neurotransmitter. It also regulates sleep/wake states, moods, cognitive functions, memory and emotions; it has the important function of inhibiting prolactin, Dopamine is a precursor to norepinephrine and epinephrine, two important neurotransmitters manufactured by the adrenal glands.
Gaba, our main inhibitory neurotransmitter, acts as a quick-intervention tranquilizer - in fact the GABA molecule is the base for many sedatives and anti-anxiety drugs.
Glutamate is the main excitatory neurotransmitter, also involved in memory and all cognition processes to include perception, judgment, problem solving, reasoning, etc.
Acetylcholine is an excitatory neurohormone that acts mainly on muscles through neuromuscular junctions; it is involved in the autonomic nervous system as both a trigger and an inhibitor.
Pituitary gland
The name originates from the Latin pituita (mucus): the gland was given its name because it was thought to channel mucus to the nose. A director of operations for the entire endocrine system, this bean-size gland, also called hypophysis, from the Greek υπόφυση (ypophysi) meaning ‘attachment below’, sits just under the hypothalamus, at the base of the cranium and behind the bridge of the nose. While it is to a large extent controlled by the hypothalamus, they both have the ability to detect the levels of hormones secreted by other glands, and assiduously intervene in their daily secretions, by releasing stimulating hormones that nudge the other glands to increase or decrease their output of hormones, in order to keep them in balance. The pituitary is composed of three parts: the posterior lobe, which is made of neuronal tissue and does not secrete hormones bur rather serves as storage for hormones released by the hypothalamus, which will later travel to the anterior lobe; the intermediate pituitary, which controls the production of skin melanin in melanocytes; the anterior pituitary, made of actual endocrine tissue, which actively releases hormones that produce responses by other glands, notably the thyroid, adrenal glands, the ovaries in women and testes in men. Thanks to its impeccable management skills, by virtue of its efficient responses in target tissues, the pituitary gland controls and influences most biological processes, such as metabolism, stress and adaptation, reproduction, sexual development, growth, body composition, cardiac functions like blood pressure and cardiac output.
Hormones released by the pituitary:
ACTH, Adrenocorticotropic Hormone stimulates the production of the steroid hormone Cortisol by the adrenal outer layer called cortex, inducing stress and immune responses, glucose/lipid/protein metabolism and modulating blood pressure. ACTH also stimulates melanin production in the skin, increasing pigmentation.]
TSH, Thyroid Stimulating Hormone, the hormone that prompts the thyroid to secrete its own hormones, namely a hormone called T4, or Thyroxine, and T3, or Triiodothyronine.
FSH, Follicle Stimulating Hormone has the important function of stimulating the growth of follicles and their hormonal secretion in the ovaries, in women and the production of sperm in the testes, in men.
LH, Luteinizing Hormone stimulates ovulation and the production of the corpus luteum in the second half of the menstrual cycle, an occurrence that leads to the production of Estrogen and Progesterone (see ovaries below). In men, LH stimulates the production of Testosterone and other sex hormones by the testes.
GH, Growth Hormone is a peptide that signals specialized liver cells to release a hormone called somatomedin-C, critical for the growth of all tissues. It controls the absorption of amino acids by the cells and their conversion to proteins; it inhibits lipogenesis, by triggering the release of fatty acids from adipose tissues so they can be burned for energy; during fasted states, GH maintains blood nutrient levels optimal.
Prolactin stimulates the production of breast milk following gestation. However, contrary to what the name may suggest, milk production is not this hormone’s only task, in fact it plays an important role in mental health, reproduction, metabolism and immunity. It inhibits dopamine, which may explain states of depression, cravings, bad habits and lack of attention in individuals who present with hyperprolactinemia, or excess prolactin.
Beta-Endorphin, one of a class of endogenous opioid neuropeptide hormones; it reduces the perception of pain and induces a state of well-being.
MSH, Melanocyte Stimulating Hormone is in charge of the production of melanin in skin and hair, but it also plays a role in appetite suppression and sexual arousal. It rises during pregnancy, reaching the highest levels during lactation.
Oxytocin originates from the hypothalamus but the pituitary is its effector organ. While its main biological function is to trigger uterine contractions during labor, oxytocin is mostly known and touted for its role in social connections, affection, sense of belonging, love and sexual intercourse.
ADH, Antidiuretic Hormone (Vasopressin) is a neurohormone that provides blood pressure upregulation through the suppression of kidney urine production and aids in conserving body fluids by inhibiting diuresis.
Thyroid gland
This small, butterfly shaped gland sits in your throat, somewhere in the posterior part of the neck and wrapped around the trachea. In men, it sits below the Adam’s apple. Thyroid conditions get a lot of press these days, and finally - and rightfully - so. The thyroid controls pretty much every single system in the body, but does so under the direction of a hierarchy, as detailed above: the hypothalamus sends TRH, thyrotropin-releasing hormone, to the pituitary gland, and the pituitary, in turn, sends a prompt to the thyroid in the form of a chemical signal called TSH, thyroid stimulating hormone. Once nudged by the pituitary, the thyroid releases hormones that reach all tissues in the body, regulating: cellular metabolism; the speed at which foods move through the GI tract; body temperature; immune responses; heart function; cognitive abilities; cholesterol production; menstrual cycles and ovulation; breathing rate; bone health; muscle function; stress and adaptive responses; skin and hair health; weight. Since the thyroid is involved in so many body processes, in articles to come I will delve into thyroid-related conditions with frequency, since poor functionality of this 2-3 inch long and 3-4 inch wide organ is both upstream and downstream of many health dysfunctions, in modern days more than ever. Suffice it to say, for now, there isn’t one biological process, change, function or dysfunction that does not involve thyroid efficiency, be it directly or indirectly, and conventional thyroid function testing is still grossly flawed, which is arguably the crux of most untreated imbalances. The indispensable building block for thyroid hormones is the iodine we get from the foods we ingest.
Hormones released by the thyroid:
T4, Thyroxine is considered the inactive and storage form of thyroid hormone. It is called T4 because it is manufactured from thyroglobulin, a modification of the amino-acid tyrosine, plus 4 molecules of iodine; for T4 to become active though, it must undergo a conversion to T3, a conversion which takes place in numerous tissues around the body, but primarily in the liver. Levels of T4 provide a feedback system for the pituitary to halt production of TSH.
T3, Triiodothyronine is the active form of thyroid hormone, and as the name suggests, it is made up of thyroglobulin plus 3 Iodine molecules. The thyroid only produces about 9 to 20 percent of T3, as opposed to the 80 percent of T4.
T2, 3,5-Diiodothyronine has recently been garnering more scientific attention for its role in metabolic health, more specifically in fatty acid oxidation, mitochondrial function and BMR, our basal metabolic rate, which it influences by increasing oxygen consumption. T2 is necessary for production of the deiodinase enzyme that helps convert T4 into T3.
T1, Monoiodotyrosine. Its physiological role was still being evaluated until very recently when it was found that T1 has an influence on the electrical input and charge of the brain and various mental disorders, including multiple sclerosis and Lou Gehrig’s syndrome, which can be a result of not enough T1 to recharge the brain.
Calcitonin’s role in the body is to ensure that calcium is used for bone tissue formation rather than depositing itself in soft tissue, which could cause damages. To do that, calcitonin ramps up production of osteoblasts, bone-forming cells, when blood calcium levels rise above 10.3mg/dl. This hormone is not under pituitary control, but rather gets secreted on a feedback system, when the thyroid detects too much calcium in the blood.
Parathyroid gland
The Parathyroid gland is actually a cluster of two pairs of oval glands, each roughly the size of a pea. It is adjacent to the thyroid, and it is in charge of maintaining calcium homeostasis in the body 24 hours a day. Though this may seem like a small role, it is in fact vital, since any small change in calcium levels in the body can cause muscle, nerve and cardiac problems. Along with the thyroid, the parathyroid plays a key role in bone health, since it is able to detect serum calcium level drops and downregulate bone formation, as needed and only until blood calcium levels go back to normal range, so calcium can be utilized for other important functions in the body. Abnormalities in parathyroid function would cause the bones to release too much calcium into the bloodstream, making bones brittle and weak, causing electric signaling to malfunction in tissues like the heart, pain and muscle weakness (among other things). Studies have shown that people whose thyroid has been removed, and therefore no longer make calcitonin, are still able to maintain bone health if the parathyroid gland exerts normal effects on bone resorption.
Hormone released by the parathyroid gland:
PTH, Parathyroid hormone gets released every time blood calcium levels fall below 8.5mg/dl. It stimulates the production and activity of osteoclasts, the cells that break bone tissue apart to ‘donate’ minerals to other organs and tissues. It also regulates the ability of the intestines to absorb Vitamin D, which is necessary for proper calcium metabolism.
Adrenal glands
Thanks to the growing business of stress management, most people have likely heard of these two tiny but powerful glands, at one point or another. The adrenals are located above our kidneys and are made up of two parts, the outer adrenal cortex, which secretes steroid hormones like cortisol and aldosterone, and the inner medulla, which secretes neurohormones like adrenaline and noradrenaline. Adrenal glands are essential to thriving, in that they are responsible for our adaptive responses to internal and external stressors, which means maintaining homeostasis, preserving life and enabling us to biologically function every day. Some of the organismal functions largely regulated by our adrenal glands include: immunity; inflammation; stress management; alertness; cognitive functions; mood, emotions and mental health; blood glucose levels; conversion of protein to energy; body fluids and blood pressure; cardiac output; cellular metabolism; weight and body composition; reproduction; sleep and recovery. As I will detail in future articles, the adrenal glands and the thyroid consistently engage in feedback behaviors orchestrated by the nervous system, hence inefficiency of one inevitably affects the other. Adrenal exhaustion, a common scourge of our times, will also be central to future investigations with relation to aging and health.
Hormones released by the adrenal glands:
Pregnenolone, an essential steroid prohormone, a term that indicates it serves biochemically as the building block for other steroid hormones such as cortisol, testosterone, estrogen and progesterone and DHEA.
Cortisol, is our stress hormone par excellence. It gets a lot of bad press these days for being a harmful hormone; its intents and effects, however, call for a clarification.
Cortisol’s actions in the body are essentially aimed at survival and life conservation, and it is known as the chronic stress hormone because it literally sustains us during trying times through a number of mechanisms, as if to save our lives. Cortisol belongs to a class of hormones called corticosteroids, in that it is manufactured from cholesterol in the cortex region of the adrenals. Its release is triggered in response to stressors, which could be anything that would destabilize or threaten homeostasis, including challenging situations perceived as positive events; its secretion is regulated at the source by the hypothalamus, through the pituitary. Cortisol rises early in the morning to give us the energy indispensable for the day, and should ideally drop by 90% at night, once the stresses of the day are over. Aging and stress interfere negatively with that drop to a significant degree, while the opposite is true: consistently high cortisol is one of the causes of premature aging.
Cortisol is an anti-inflammatory hormone: it decreases fluid build-up at the site of insult and modulates the immune response by suppressing T-cells and antibodies as needed. Cortisol is also categorized as a glucocorticoid, indicating it is involved in carbohydrate catabolism and metabolism: when cortisol levels rise, the rate of gluconeogenesis, which is the synthesis of carbohydrates from other substrates like amino acids, also rises by six to tenfold, increasing glycogen stores in the liver that could be readily accessed in case of increased needs for energy. Cortisol also stimulates the breakdown of lipids in adipose tissues for the same reason, which is to make extra energy readily accessible if need be, and downregulates the uptake of protein and glucose by the cells, to inhibit tissue building and save fuel instead.
However, on the flip side, during states of prolonged exposure to stressors and consequent sustained secretion, and in the absence of physical activity, cortisol can interact with estrogen and insulin, which leads to increased food intake and storage, and the redistribution of stored energy from muscle to fat tissues, primarily around central organs (visceral fat), causing fat cells to grow and mature. Since cortisol also mobilizes amino acids from muscles in its catabolic/fuel saving efforts - hence providing more substrates for gluconeogenesis - a decrease in RMR, resting metabolic rate, ensues. To make matters worse, cortisol flooding leads to increased cravings, stimulant consumption, food sensitivities and impaired ability to absorb nutrients in the intestines.
Aldosterone is the main mineralocorticoid, a class of hormones that have the ability to regulate the concentration of sodium and potassium in bodily fluids, regulating osmolality. Aldosterone is released in response to elevated blood potassium levels, low blood pressure and low blood volume, which it counteracts by increasing potassium excretion and sodium retention. While the response to blood potassium levels is direct, it is the kidneys that control its release in response to blood pressure and volume. In times of stress, it is secreted upon hypothalamic and pituitary cueing.
DHEA, Dehydroepiandrosterone is a steroid hormone and a precursor to other sex hormones, namely testosterone and estrogen, with important implications in our immunocompetence. DHEA peaks in our twenties and begins to wane thenceforth, and for that reason it is touted as a youth hormone. DHEA replacement therapy is being investigated for its plausible anti-aging, antioxidant, anti-inflammatory and immunity boosting effects. DHEA and Cortisol have an inverse relationship: when levels of one go up, the other one goes down - for instance, DHEA sparks the immune response and Cortisol suppresses it.
Adrenaline (Epinephrine) is produced in the adrenal glands as well as in the medulla oblongata (brain region). It is considered both a stress hormone and the main neurotransmitter acting in our fight-or-flight-or-freeze quick response to a perceived threat; this hyperarousal is an evolutionary mechanism stemming from basic survival instincts, but in times of stress adrenaline is released in response to fear, stress and anxiety. Adrenaline ramps up the sympathetic nervous system, the one in charge of our unconscious actions, to prime the body to either fight or flee from harm. To rouse the body in the face of a sudden crisis, adrenaline increases cardiac output and breathing rate, and dilates air passages to amplify oxygen transport to limb muscles, heart and lungs; it urges the liver to release more blood sugar, to make energy readily available; it sharpens the senses, particularly eyesight by dilating pupils, to increase alertness; it reduces the perception of pain, so we can continue fighting if we are injured. Overexposure to adrenaline is detrimental to our health.
Noradrenaline (Norepinephrine) belongs to a class of hormones called catecholamines, chemicals that function as both hormones and neurotransmitters, along with adrenaline and dopamine. The main difference between adrenaline and noradrenaline is that the latter is also released directly by the sympathetic nervous system. Adrenaline is produced in greater quantities—approximately a 4 to 1 ratio with noradrenaline, however NA works alongside its counterpart as a coadjutant in the stress response. Noradrenaline also has several important daily biorhythmic functions: it increases tear production and pupil dilation in response to light and emotions; it triggers the release of glucagon by the pancreas when blood sugar levels are low; it helps the lymphatic system fight infections; it controls the speed at which food goes through the GI tract, slowing it down if need be;it assists in regulating salt/water balance by acting on the kidneys to secrete renin; it regulates blood flow to skeletal muscles; it sustains moods and emotional well-being.
Androstenedione is a steroid hormone with weak androgenic action of its own, but it is important because it gets rapidly converted into testosterone and estrogen in various tissues, making it a back-up supplier for post-menopausal women.
Pancreas
The pancreas is located in the abdominal cavity behind the stomach, and functionally it belongs to both the endocrine system and the digestive system. This glandular organ is primarily in charge of maintaining blood sugar homeostasis in the body, by impacting the rate at which glucose is utilized for energy, as well as its storage and release via the liver. It is in fact considered as both an endocrine organ, in that it secretes hormones that are sent out into the bloodstream, and an exocrine organ, since it secretes enzymes through ducts directly onto epithelial tissue. Through the release of insulin, the pancreas also controls the sodium-potassium balance in the body.
Hormones released by the pancreas:
Insulin [Insulin is one of the main anabolic hormones, and is hence labeled as the storage hormone. When you ingest carbohydrates, they get broken down by digestion into glucose molecules, so they can be utilized to produce energy. When blood sugar levels rise, the pancreas secretes insulin to dispatch that glucose to the tens of trillions of cells around the body, so it can either be used for fuel or stored in the form of a glucose reserve called glycogen, in the liver and muscles. To get the job done, insulin solicits special receptors located on the cell walls that literally let the glucose in when insulin ‘knocks’. The more carbohydrates are ingested, the harder the pancreas has to work to pump out insulin, in order to keep the blood from getting saturated with glucose - a very dangerous situation that can lead to coma and death. Since insulin also prompts the liver to store glycogen, in states of high insulin and consequent excess glycogen production, the liver runs out of storage space and converts glucose into fatty acids and triglycerides instead, causing fat accumulation. Additionally, insulin also inhibits the activity of an enzyme called Hormone Sensitive Lipase, HSL, which mobilizes stored fats so they get burned off. Aside from glucose, insulin is known to escort amino acids and fatty acids into cells, albeit to a significantly lesser degree than glucose, but it is also responsible for ushering potassium into the cells by activating the cell sodium-potassium pump.]
Glucagon, produced during fasted states, and when there is a glucose drop in the blood 4 to 6 hours after a meal, the pancreas releases glucagon; it is considered insulin’s antagonist. Glucagon triggers glycogenolysis, which is the reconversion of glycogen to glucose in liver and muscle cells, and its release into the bloodstream to restore normal glucose levels.
Somatostatin, also produced in the hypothalamus and the gut, restrains production of other hormones such as: growth hormone, which is also conversely called somatotropin, in humans; cortisol; prolactin; TSH; glucagon and insulin; gastric CCK. Through its inhibitory actions, somatostatin balances digestion, metabolism, growth and several other functions in the body.
Vasoactive intestinal peptide (VIP), a peptide hormone that gets released by the pancreas along with insulin, particularly after the ingestion of protein and fats, and stays high for 4 to 6 hours. It is involved in digestion and appetite regulation in more ways than one: it sends a signal of satiety to the brain; it relaxes the gallbladder, hindering bile production, thus reducing the speed at which food moves through the digestive tract; it inhibits the production of certain pancreatic enzymes, slowing down digestion.
Ovaries
The ovaries are the female gonads, primary sexual reproductive organs. They are a set of two oval shaped glands, each roughly the size of a large olive, and each located on one side of a woman’s uterus, left and right of the pelvic region. The ovaries carry out a dual function: they store eggs (ova or oocytes) for fertilization inside the follicles, (tiny fluid filled sacs), and from the released eggs they manufacture the two main reproductive sex hormones, estrogen and progesterone.
Reproductive hormone secretion in the ovaries is dependent on and synchronized with the menstrual cycle, which occurs in intervals of approximately 28 days (though many women present with shorter or longer cycles), each in 3 phases:
1.The follicular phase, which kicks off the development of the egg at day 1 of the cycle, when the bleed starts, overlapping with actual menstruation. In the follicular phase, the hypothalamus sends a signal via its GnRH, gonadotropic-releasing hormone, to the pituitary, which in turn secretes FSH, follicle stimulating hormone. FSH is sent to the ovaries to stimulate the growth of about 15-20 follicles, causing the eggs inside of them to mature; only one egg will reach full maturity and be released.
2. The ovulatory phase, or release of the ‘lucky’ egg, which happens at day 14 of a 28 day cycle - though individual timing variations are often seen. Under that same hypothalamic nudge, at mid-cycle the pituitary sends another strong signal in the form of LH, luteinizing hormone, which triggers the discharge of one dominant, fully matured egg by quickly spurring growth and development of both the follicle and the egg. The egg then travels to the uterus through the fallopian tubes, which are narrow tubes that connect ovaries and uterus: if the egg is fertilized by sperm in the process, it then implants itself in the lining of the uterus (thickened and enriched by hormones in preparation for a potential pregnancy), and it continues to develop into a fetus.
3. The luteal phase, which is considered the post-ovulatory phase and sets off a drop in hormones if fertilization does not occur. LH stays high for about 24 hours, and starts to decline from that point on. If the egg is not fertilized, the lining of the uterus sheds, causing a bleed - this marks day one of the following menstrual cycle, and FSH starts to rise again.
Hormones released by the ovaries:
Testosterone is an androgen steroid, in fact it is mostly known as the male sex hormone, but it is vital for both men and women. This compound has several functions in a female body: it grows and maintains lean body mass; it assists in bone formation and in maintaining bone density; it increases skeletal muscles strength and exercise endurance; it aids in the production of new red blood cells; it is the main hormone involved in sexual arousal; it sustains emotional health by enhancing mood, motivation, drive and general well-being; it improves the quality of sleep. The production of testosterone is regulated by hypothalamic GnRH and pituitary LH.
Estrogen, synthesized from testosterone and an enzyme called aromatase during the follicular phase of the menstrual cycle, starts to rise around day 5 of the cycle. As detailed above, pituitary FSH stimulates ovarian follicle development, so the selected eggs can start to mature; the so-called granulosa cells around the maturing eggs start producing estrogen in preparation for a potential pregnancy: estrogen is the hormone that makes the endometrial lining of the uterus thick and plump to accommodate the fetus. Once the follicles have produced enough estrogen, a negative feedback system alerts the pituitary to decrease FSH and start producing LH, which triggers ovulation, the release of the one egg that made it to the finish line. If that egg is not fertilized and pregnancy does not occur, estrogen drops sharply right after ovulation takes place. There are estrogen receptors all over the body: estrogen is the hormone of growth and prosperity, the one that develops breast tissues at puberty and gives a woman her female attributes. It is the hormone that increases women’s sex drive; it keeps bones strong; it bolsters brain function by promoting neurogenesis; it supports blood circulation by boosting production of NO (nitric oxide), which makes it a precious safeguard in heart health; it aids digestion; it keeps skin smooth and plump by retaining beneficial moisture; it increases body mucosal membranes in the eyes, lips and vagina; it has anti-inflammatory and anti-oxidant properties.
It is important to note that estrogen is actually a family of hormones, the main ones being estrone, estradiol, and estriol. Estradiol (E2) is the type of estrogen secreted by the ovaries before menopause, while in post-menopausal women estrone is produced in fat cells and adrenal glands. Since the metabolism of estrogens is complex and impacted by other hormones, the subject of estrogens will be covered in a separate article detailing menopause and estrogen-related conditions.
Progesterone has a great reputation for being the hormone that gives pregnant women their proverbial glow, which is in fact due to its plumping and regenerative effects on the skin. After the dominant egg is released into the fallopian tubes, the remaining portion of the follicle seals itself, forming a mass of cells called corpus luteum, which produces progesterone. During pregnancy, it is also produced by the placenta to prime the uterus so pregnancy can be carried to term by increasing blood flow to the endometrium, relaxing the smooth muscle in the uterine wall to prevent dangerous contractions, and stimulating the cells of the uterine lining to produce a fluid that contains nutrients the embryo will need. Progesterone levels during pregnancy increase 100 fold in the placenta and 10-fold in the bloodstream. Generally speaking, progesterone has tremendous beneficial effects in the body: it has a calming effect on the nervous system, promoting healthy sleep patterns; it supports a healthy immune response and plays a protective role against auto-immune conditions; it enhances and supports thyroid function, hence metabolism; it has a protective role in heart health; it promotes neurogenesis, supports memory and emotional well-being; lastly, it supports mitochondrial function and has anti-inflammatory properties.
Progesterone is also a precursor hormone, meaning it is used to manufacture and get converted into other steroid hormones like cortisol, testosterone and DHEA. For instance, progesterone is used to make cortisol, particularly in times of stress and adrenal exhaustion, but since cortisol and progesterone compete for the same receptors, when cortisol levels rise exceedingly in response to chronic stress, progesterone levels drop, causing a rise in estrogens which blocks thyroid function. The conversion and interaction pathways involving progesterone and other hormones are complex and will be explored later in this endocrine system investigation, from a functional nutrition perspective.
Since the corpus luteum is a temporary ovulatory endocrine gland, in menopausal women the task of producing progesterone is picked up by the adrenals.
Testes
The testes, or testicles, are a set of two male endocrine glands that play a paramount role in men’s sexual health, their reproductive capability and many other functions in the body. They are egg-shaped organs located inside the scrotum, which is a sac underneath and behind the penis; the scrotum is suspended from the abdomen by the spermatic cords, also called testicular cords (one for each testicle). Blood vessels, arteries, nerves and lymph vessels in the spermatic cords protect the health of the testes, and contain the ductus deference, which channels out semen during ejaculation. The two main functions of the testes are hormone secretion and sperm production.
Hormones released by the testes:
Testosterone, as previously discussed, is a steroid androgen hormone present in both male and female bodies. In men, it is produced in the Leydig cells, upon signaling by pituitary LH, Luteinizing Hormone. Testosterone is the hormone responsible for sex differentiation, the process by which a fetus develops into a male or female, and the development of secondary sexual characteristics in puberty, such as the onset of phenotypic traits like muscular build, deep voice, facial and body hair, and Adam's apple.
However, testosterone also exerts a plethora of vital functions in the body: it is a cardio-protective hormone; it grows muscle tissue and bone mass; it increases physical strength and exertional capacity; it stimulates sperm production, sex drive and endurance; it enhances cognitive functions, supports emotional health and logical thinking, and boosts motivation and drive; it regulates the production of red blood cells. A small amount of testosterone is naturally converted to estradiol through the action of an enzyme called aromatase; aging, stress and poor lifestyle habits may upregulate the conversion to estradiol irreversibly and throw the hormonal balance off in favor of estrogen, causing middle weight gain and a host of other metabolic issues, including erectile dysfunction.
Progesterone is produced in small amounts in the testes and adrenals in men. Although not enough attention is placed on progesterone in men, it has important implications in men’s health: it improves sleep in men who present with sleep apnea; it regulates fat oxidation in muscles; it stabilizes thyroid hormone production; it supports bone formation; it aids in neurogenesis, supporting cognitive functions and emotional well-being; it blocks the secretion of GnRH, Gonadotropic-releasing hormone, from the hypothalamus, regulating testosterone production; it modulates the immune response and has an anti-inflammatory action; it regulates kidney function.
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Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034117/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034117/
https://www.researchgate.net/publication/327799271_Circadian_and_Circannual_Rhythms_and_Hormones
https://pubmed.ncbi.nlm.nih.gov/9343306/
https://pubmed.ncbi.nlm.nih.gov/9008662/
https://jhu.pure.elsevier.com/en/publications/adrenal-androgens-and-the-immune-system-3
https://pubmed.ncbi.nlm.nih.gov/11549649/
https://academic.oup.com/jcem/article/92/1/322/2598803