What endocrine glands are there?

The small gland deep between the cerebral cortex and cerebellum at the back of the third ventricle in the middle of the brain is the pineal gland. The hypothalamus produces neurohormones, neuropeptides and neurotransmitters, and these partly control most of the endocrine glands. Down from the hypothalamus, at the base of the brain, the pituitary gland sits in a small cavity of bone above the roof of the mouth.

In the neck we find the thyroid gland and in the surface of the thyroid the parathyroid glands. The thymus gland is located in the chest. It is important for the immune response, because of its production of T lymphocytes. The heart and lungs also act as endocrine glands to secrete hormones. Another important source of hormones is the gastrointestinal (GI) tract, composed of the stomach and intestines. The liver secretes hormones important for growth (somatomedin). On top of the kidneys lie the adrenal glands. The pancreas produces hormones that regulate the blood sugar levels and the kidney produces hormone-like chemicals.

Gonadal hormones are produced by the testes and ovaries. They maintain fertility and sexual characteristics, but also have effects on behaviour. The placenta acts as an endocrine gland during pregnancy. All vertebrates have endocrine glands at nearly the same places. Adipose tissue is a fatty large endocrine gland under the skin, in the abdominal cavity around the heart and GI tract and in tissues such as the liver and muscle. Fat secretes hormones called adipokines. Skeletal muscle and bone are the largest tissues of the body and act in an endocrine manner.

Which hormones are important for the endocrine glands?

Melatonin

The pineal gland secretes melatonin, particularly during nighttime. It presumably improves sleep patterns, jet lag, and helps in the management of depression, epilepsy, Alzheimer’s disease, diabetes, obesity, migraine and cancer. Melatonin mediates reproductive activity in response to changes in environmental light cycles. In non-mammalian vertebrates it causes lightening of pigment coloration.

Hormones of the hypothalamus and pituitary gland

The hypothalamus secretes hormones, neuropeptides and neurotransmitters that regulate the secretion of nine hormones of the pituitary gland.

The thyroid gland hormones

The thyroid gland produces triiodothyronine (T3) and thyroxine (T4), which are quite similar in structure and are synthesised by iodine in food. T4 is more prevalent in the blood, but in all target tissues it is converted to T3. So T4 is a prohormone for T3. The hormones regulate metabolic rate and have a role in brain development and maturation and bone growth. ‘Congenital hypothyroidism’ is the congenital lack of thyroid hormones, which results in enormously reduced brain development. Another hormone produced by the thyroid gland is calcitonin which reduces blood calcium levels.

In the posterior part of the thyroid glands there are four small parathyroid glands. The blood calcium level is elevated by the parathyroid hormone secreted by the parathyroid gland, because calcium is released from bone and calcium is reabsorbed into the blood through the kidneys and the gut. This is called hormonal feedback. Hormones are often secreted in pairs with opposite functions. In this case calcitonin lowers the blood calcium levels and parathyroid hormones elevate it.

Thymosins

The thymus produces thymosins, which lead to production and differentiation of lymphocytes in the immune system and release cytokines. The development of T cells is dependent on the thymus gland, because thymosins convert pre-thymic cells into T lymphocytes. Thymosins also have a role in developing immunocompetence, which is the ability to respond to antigenic stimulation. The antibodies, produced neonatally, also rely on the thymus. There is a lot of interaction between endocrine, neural and immune systems in the thymus gland. The thymosins have autocrine/paracrine functions in the thymus and endocrine functions in the blood.

Heart and lungs

To reduce the blood pressure the heart produces atrial natriuretic peptide (ANP), which causes vasodilation and action on the kidney, namely less reabsorption of water and sodium ions. As a neuropeptide in the brain, ANP regulates the salt and water intake, heart rate and vasopressin secretion. The B-type natriuretic peptide (BNP) has the same function as the ANP, but high levels of BNP could indicate congestive heart failure.

The lungs produce neuropeptides, such as cholecystokinin and peptide YY. They regulate growth and development of the airways and might be involved in pathologies.

Gastrointestinal tract

The gastrointestinal (GI) system secretes over 20 hormones. They are released from endocrine cells and have functions in contraction or relaxation of the smooth muscle walls and sphincters, release of digestive enzymes and release of fluids and electrolytes. They all act in different ways; as endocrine hormones at distant sites, in paracrine manner or in neuroendocrine manner. Three well known GI hormones are gastrin, secretin and cholecystokinin.

Gastrin is produced as a response to distension by eating a meal. It stimulates the secretion of hydrochloric acid in the stomach and the secretion of pancreatic enzyme and it increases intestinal motility. Gastrin is important for digesting food. An example of a gastrin hormone is cholecystokinin, which is released in the presence of food. It stimulates the contraction of the gall bladder and secretes pancreatic enzyme secretion. As a neuropeptide in the brain it reduces food intake.

Secretin is released when partially digested food is transferred from the stomach to the duodenum. It stimulates the secretion of pancreatic bicarbonate and is important in digestion. Many GI hormones have a function in the ‘gut-brain axis’, which indicates the interactions between the gastrointestinal tract and the brain. They work as neuropeptides to regulate energy homeostasis, hunger and appetite. CCK for instance regulates energy homeostasis. Ghrelin increases appetite via the circulation. When fasting, the ghrelin blood levels are high and after a meal they are reduced. Obesity might be prevented by blocking the effects of ghrelin. It could also help to stimulate appetite in people needing to gain weight.

Peptide YY blood levels increase after food restriction and decrease after meals. It could be useful as an anti-obesity drug, because injection of PYY can reduce the food intake. The preproglucagon molecule produces smaller peptides, such as glucagon, glucagon-like peptide-1 (GLP-1) and GLP-2. The GI peptide GLP-1 increases after a meal and stimulates insulin secretion from the pancreas. GLP-1 might be able to suppress appetite to control body weight, especially in Type 2 diabetes. GLP-2 doesn’t affect appetite, but has effects on growth, motility and blood flow. The GI tract secrete even more peptides, see table 2.2, reader p.39. many of the gastrointestinal peptides also act as chemical signals in the enteric nervous system, a branch of the autonomic nervous system.

The islets of Langerhans

The islets of Langerhans, small clusters of endocrine cells in the pancreas, are divided in four types:

• β-cells, which produce insulin when the blood glucose levels have increased. This leads to the uptake of glucose in the fat, liver or muscle cells. The glucose is stored as glycogen or used as a source for energy;

• α-cells, which release glucagon. This hormone increases the blood glucose levels by leading to the conversion of glycogen to glucose in the liver;

• somatostatin, which is made by the δ cells and reduces the secretion of glucagon and insulin via a paracrine mechanism. The hypothalamus also contains somatostatin, where it has a function of inhibiting growth hormone secretion;

• pancreatic polypeptide, which is made in the F cells. After eating food the blood levels of PP increase.

The adrenal cortex and medulla

The adrenal cortex secretes three types of hormones: mineralocorticoids, glucocorticoids and sex steroids. The main mineralocorticoid is aldosterone. When sodium ions in the blood decrease the amount of aldosterone increases. Its function is to increase the reabsorption of sodium ions in the kidneys, salivary glands and sweat glands.

The anterior pituitary gland produces adrenocorticotropic hormone (ACTH), which then stimulates the release of glucocorticoids (cortisol in humans). When stressing, glucocorticoids are released to stimulate the synthesis of glycogen and glucose in the liver, to increase the metabolism of carbohydrates and fasts, to activate the neural stress response and to suppress the activity of the immune system. Another function of glucocorticoids is inhibiting inflammatory and allergic reactions and the inhibiting the production of lymphocytes by the immune system. It can be used to treat arthritis and so transplants will not be rejected. However excessive glucocorticoids are not good for the body, since it affects tissues, which can result in for instance insulin resistance and increased deposition of fat. It can also damage neurons and lead to neuron death via apoptosis. Other hormones produced by the adrenal cortex are estradiol and testosterone, which influence sexual differentiation and secondary sexual characteristics in puberty.

The adrenal medulla communicates in a neuroendocrine fashion. The sympathetic branch of the autonomic nervous system controls the secretion of hormones by the adrenal medulla. Epinephrine is produced during stress within the adrenal medulla and increases the heart rate and blood glucose levels. Norepinephrine is secreted to increase the blood pressure by constricting the blood vessels.

Vitamin D and erythropoietin

The skin synthesizes two prohormones when exposed to sunlight. These get metabolised by the liver and kidneys to form 1,25-dihydroxyvitamin D, or calcitriol. PTH and calcitriol together maintainnthe blood calcium levels. It is also important for bone mineralisation and calcium absorption from the gut. Enough calcitriol is necessary to maintain good bone strength, immune response and cancer prevention. Erythropoietin is also secreted by the kidneys and acts on bone marrow for the production of red blood cells. It can be used for several treatment purposes: kidney failure, AIDS and prevention of neural apoptosis.

The testes and ovaries

The testes contain Leydig cells and Sertoli cells. Leydig cells produce androgens, responsible for the male sexual characteristics. The main androgen is testosterone, which can function as a prohormone, being converted into dihydrotestosterone or estradiol. Testosterone masculinizes the genitalia, controls the production of sperm, develops the secondary male sexual characteristics and activates sexual and aggressive behaviours. The Sertolie cells produce inhibin and activing. Inhibin inhibits the follicle-stimulating hormone (FSH) secretion and activing can oppose these effects.

The granulosa cells of the ovarian follicle produce estradiol, a type of oestrogen, which is responsible for the development of female sex characteristics, uterine function and the menstrual cycle and pregnancy. Estradiol also influences mood, body temperature, skin texture and fat distribution; protects the heart and bone density; and influences sexual and parental behaviours in the female.

The Luteal cells of the ovary produce progesterone, inhibin, activin and relaxin. Progesterone is important for the uterine, vaginal and mammary gland growth. It prepares the uterus for implantation of a fertilised egg during the menstrual cycle and maintains a pregnancy by inhibiting the menstrual cycle and sexual behaviour associated with it. For progesterone to have an effect, estradiol must have acted upon the target first. Inhibin inhibits the FSH secretion, while activing stimulates it. When inhibin is present in abnormally high amounts it can be a marker for the diagnosis of pre-eclampsia and Down’s syndrome. Relaxin is only present in pregnancy and acts on the uterine lining.

The placenta

The placenta produces many hormones for the maintenance of the pregnancy. The first hormone, that is produced in the beginning of the pregnancy, is human chorionic gonadotropin (HCG). Detecting this hormone works as a pregnancy test. HCG makes sure the corpus luteum of the ovaries produce progesterone to maintain the uterine lining. Without progesterone the pregnancy would be aborted, because the placenta would not be able to develop. Later in the pregnancy the placenta will develop its own progesterone.

In the maternal-feto-placental unit a lot of hormones are produced for maintaining the pregnancy. One such hormone is human placental lactogen (HPL) or human chorionic somatomammotropin (HCS).it stimulates the differentiation of the mammary glands for the manufacturing and secreting of milk. The placenta also produces steroid hormones, pituitary-like hormones, neuropeptides and biogenic amines. Relaxin is secreted at the end of the pregnancy to prepare the birth canal for parturition. It makes the cervix more flexible for the birth.

Fat tissue

There are two types of fat tissue: white adipose tissue secreting adipokines and brown adipose tissue. White adipose tissue produces leptin and resistin. Leptin reduces food intake and prevents an increase in body fat by stimulating leptin receptors in the hypothalamus for a reduction in appetite and increased energy expenditure. Leptin reduces the perception of food reward and enhances responses to satiety signals that inhibit feeding and lead to meal termination. When losing weight, the leptin levels decrease, which is why the rewarding properties of food increase and the satiety reduces. Therefore more food is eaten. When leptin is missing, it can be taken as a treatment. In obese people there seem to be elevated levels of leptin. However, it doesn’t work the same way it does in thinner people. This is because the hypothalamus receptors are a bit desensitised and don’t respond well to leptin feedback.

Resistin is involved in insulin resistance, obesity, diabetes and hypertension. Together with adiponectin it modifies insulin signalling and regulates the onset of diabetes. There are many other hormones secreted by adipose tissue, such as adipsin, visfatin, cytokines, prostaglandins and steroid hormones estradiol and cortisol.

Skeletal muscles

The hormones secreted by skeletal muscle communicate with other organs. The blood levels of interleukin-6 (IL-6) increase during exercise. It has an important effect on fat cells. Fat tissue function is also modulated by myostatin. Blocking the action of myostatin might be helpful in preventing obesity. Irisin also regulates fat tissue and is secreted from the skeletal muscle during exercise. It stimulates the production of brown adipocytes within white fat depots, called ‘browning’. This promotes energy expenditure through thermogenesis.

When irisin levels are heightened there is an increase in browning of fat tissue, as well as an increase in energy expenditure, weight loss and improvements in diabetic state. The heart muscle hormones, ANP and BNP, also induce brown fat cells to increase thermogenesis. Therefore tissues involved in high physical activity might send endocrine signals to fat cells.

Bone

Bone is a target for many hormones:

• parathyroid hormone causes calcium ions from bone to be released into the blood;

• bone mass is maintained through estradiol;

• IGF-1 regulates bone growth.

Bone itself also secretes hormones. The major hormone, secreted from osteoblasts, is osteocalcin. It has four main effects:

• increasing production of testosterone by the testes;

• stimulating proliferation of pancreatic β cells producing insulin;

• increasing the release of insulin from β cells;

• increasing insulin sensitivity of muscle, liver and fat cells and stimulating energy expenditure by muscle.

Absence of osteocalcin could result in a diabetic state, reversible through treatment with osteocalcin. Osteocalcin regulates glucose homeostasis, energy expenditure and fertility.

The liver

The liver produces fetuin-A, fibroblast growth factor-21 (FGF-21) and betatrophin, which are hepatokines. Fetuin-A is secreted when there is chronic over-nutrition and high glucose levels. It reduces insulin receptor signalling on skeletal muscle and liver. Therefore tissues can’t take up glucose and a diabetic state is induced. FGF-21, in mice, increases insulin sensitivity and muscular uptake of glucose. In humans, however, FGF-21 reduces insulin sensitivity. In mice, it acts as a starvation indicator and can be responsible for fasting-induced inhibition of reproduction by affecting the hypothalamus. Betatrophin heightens β-cell proliferation and output of insulin.