Other Endocrine Tissues and Organs

Eicosanoids

The eicosanoids are signaling molecules that exert complex control over many bodily systems, mainly in inflammation or immunity.

Learning Objectives

Describe the synthesis and function of eicosanoids

Key Takeaways

Key Points

  • Eicosanoids are signaling molecules made by the oxidation of 20-carbon   essential fatty acids (EFAs).
  • Eicosanoids derive from either omega-3 or omega-6 EFAs.
  • Omega-6 eicosanoids are generally more pro-inflammatory than omega-3 eicosanoids.
  • Anti-inflammatory drugs such as aspirin act by down-regulating eicosanoid synthesis.
  • There are four families of eicosanoids: prostaglandins, prostacyclins, thromboxanes, and leukotrienes.

Key Terms

  • omega-6: Fatty acids (also called ω6 fatty acids or n−6 fatty acids) that are commonly found in poultry and plant oils.
  • omega-3: Fatty acids (also called ω3 fatty acids or n−3 fatty acids) that are commonly found in marine and plant oils.
  • essential fatty acid: Any fatty acid required for the human metabolism that cannot be synthesized by the body and that must be present in the diet; it was originally designated as vitamin F.

In biochemistry, eicosanoids are signaling molecules made by oxidation of 20-carbon essential fatty acids (EFAs). The networks of controls that depend upon eicosanoids are among the most complex in the human body.

Eicosanoids are derived from either omega-3 (ω-3) or omega-6 (ω-6) EFAs. The ω-6 eicosanoids are generally pro-inflammatory; ω-3s are much less so. An excess of
ω-6 to ω-3 fatty acids is common in western diets and is thought to encourage certain inflammatory disorders such as arthritis, cardiovascular disease, and cancers of the digestive system.

There are four families of eicosanoids:

  1. Prostaglandins
  2. Prostacyclins
  3. Thromboxanes
  4. Leukotrienes

For each, there are two or three separate series, derived either from an ω-3 or ω-6 EFA. These series’ different activities largely explain the health effects of ω-3 and ω-6 fats.

Biosynthesis

Two families of enzymes catalyze EFA oxygenation to produce the eicosanoids:

  1. Cyclooxygenase, or COX, which generates the prostanoids.
  2. Lipoxygenase, or LOX, in several forms.

Eicosanoids are not stored within cells; they are synthesized as required. They derive from the EFAs that make up the cell and nuclear membranes. Biosynthesis is initiated when a cell is activated by mechanical trauma, cytokines, growth factors, or other stimuli.

Function and Pharmacology

Eicosanoids exert complex control over many bodily systems, mainly in inflammation or immunity, and as messengers in the central nervous system. Eicosanoids typically act as local hormones, acting on the same cell or nearby cells and then are rapidly inactivated.

Anti-inflammatory drugs such as aspirin and other NSAIDs act by down-regulating eicosanoid synthesis to prevent local and systemic inflammation.

This is a diagram that shows the pathways in the biosynthesis of eicosanoids from arachidonic acid.

Biosynthesis of eicosanoids: Pathways in the biosynthesis of eicosanoids from arachidonic acid.

Growth Factors

A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation, and cellular differentiation.

Learning Objectives

Describe growth factors in terms of cytokines and hormones

Key Takeaways

Key Points

  • Growth factors, cytokines, and hormones are all chemical messengers that mediate intercellular communication.
  • A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation, and cellular differentiation.
  • A cytokine is a small protein involved in cell signaling.
  • A hormone is any member of a class of signaling molecules that is secreted by ductless glands and are transported by the circulatory system.
  • Cytokines and hormones are not always growth factors.

Growth factors, cytokines, and hormones are all chemical messengers that mediate intercellular communication. Confusion arises due to their overlaps in function and definition.

Growth Factors

A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation, and cellular differentiation. An example is granulocyte macrophage colony-stimulating factor (GM-CSF), a growth factor that stimulates the production of white blood cells. Growth factors are typically cytokines or hormones, but not all cytokines and hormones are growth factors.

Cytokines

A cytokine is a small protein involved in cell signaling. Some cytokines are involved in growth, such as GM-CSF, and so are classed as growth factors, but many others are not. Confusingly, cytokine and growth factor are sometimes used as interchangeable terms.

A cytokine differs from a hormone in that it is not secreted from a gland.

Hormones

A hormone is any member of a class of signaling molecules secreted by ductless glands that are transported by the circulatory system. As with cytokines, some are involved with growth, such as the growth hormone produced by the anterior pituitary gland, and may be classed as growth factors, but others are not.

Hormones are secreted from specialized ductless glands into the circulatory system, differentiating them from cytokines.

This chart shows the complexity of interactions, and the multitude of growth factors that stimulate proliferation and differentiation of cells that is common to all cell types. The majority of growth factors shown above are cytokines such as GM-CSF, however the hormone EPO secreted by the kidney plays a key role in erythrocyte (red blood cell) proliferation.

Hematopoiesis as it occurs in humans, with important hemopoietic growth factors affecting differentiation: This chart shows the complexity of interactions, and the multitude of growth factors that stimulate proliferation and differentiation of cells that is common to all cell types. The majority of growth factors shown above are cytokines such as GM-CSF, however the hormone EPO secreted by the kidney plays a key role in erythrocyte (red blood cell) proliferation.

Other Hormone-Producing Structures

Many tissues within the body release hormones including the placenta, kidneys, digestive system, and adipose tissue.

Learning Objectives

Differentiate among the non-glandular, hormone-producing structures of the endocrine system

Key Takeaways

Key Points

  • There are several other organs in the body that secrete hormones although they are generally not thought of as being part of the endocrine system.
  • The kidneys secrete many hormones that help maintain blood pressure and volume, including erthyropoietin, calcitriol, and atrial natriuretic hormone, as well as several proteins and enzymes.
  • The heart secretes atrial natriuretic hormone to reduce blood pressure.
  • Many hormones are released in the digestive system to help in the absorption and break down of food, including gastrin, secretin, and cholecystokinin.
  • Adipose tissue, or fat, is a major endocrine organ and produces hormones such as leptin and estrogen.
  • The placenta secretes several important hormones in pregnancy, including human chorionic gonadotropin, human placental lactogen, estrogen, and progesterone.

There are several other organs in the body that secrete hormones although they are generally not thought of as being part of the endocrine system.

The Kidneys

The kidneys secrete a variety of hormones, including erythropoietin, and the enzyme renin. Erythropoietin is released in response to hypoxia in the renal circulation. It stimulates erythropoiesis (production of red blood cells ) in the bone marrow. Part of the renin-angiotensin- aldosterone system, renin is an enzyme involved in the regulation of aldosterone levels.

The Heart

Atrial natriuretic hormone (ANH) is a powerful vasodilator and a protein hormone secreted by heart muscle cells. It is involved in the homeostatic control of body water, sodium, potassium, and fat.

ANH is released by muscle cells in the upper chambers (atria) of the heart in response to high blood pressure. ANH acts to reduce the water, sodium, and adipose loads on the circulatory system to reduce blood pressure.

Stomach and Small Intestine

There are at least five hormones that aid and regulate the digestive system in mammals.

  • Gastrin is in the stomach and stimulates the gastric glands to secrete pepsinogen (an inactive form of the enzyme pepsin) and hydrochloric acid. Secretion of gastrin is stimulated by food arriving in the stomach. The secretion is inhibited by low pH.
  • Secretin is in the duodenum and signals the secretion of sodium bicarbonate in the pancreas and it stimulates the secretion of bile in the liver. This hormone responds to the acidity of the chyme.
  • Cholecystokinin (CCK) is in the duodenum and stimulates the release of digestive enzymes in the pancreas and stimulates the emptying of bile in the gall bladder. This hormone is secreted in response to fat in chyme.
  • Gastric inhibitory peptide (GIP) is in the duodenum and decreases the stomach churning, which in turn slows the emptying in the stomach. Another function is to induce insulin secretion.
  • Motilin is in the duodenum and increases the migrating myoelectric complex component of gastrointestinal motility and stimulates the production of pepsin.

Adipose Tissue

Adipose, or fat, tissue is loose connective tissue composed of adipocytes. Its main role is to store energy in the form of lipids, although it also cushions and insulates the body.

Adipose tissue has in recent years been recognized as a major endocrine organ, as it produces hormones such as:

  • Leptin, which targets the hypothalamus and is important in regulating food intake.
  • Estrogen, which plays a key role in sexual function.
  • Resistin, which targets several tissues with unknown function.

The Placenta

The placenta endocrine function in humans, aside from serving as the conduit for oxygen and nutrients for the fetus, secretes hormones that are important during pregnancy, such as human chorionic gonadotropin, human placental lactogen, estrogen, and progesterone.

Male and Female Gonads

The gonads in males are the testes and the gonads in females are the ovaries.

Learning Objectives

Compare the roles played in the endocrine system by the male and female gonads

Key Takeaways

Key Points

  • The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system.
  • Ovaries secrete both estrogen and progesterone, and also androgens such as testosterone.
  • The testicle is the male reproductive gonad in humans.
  • The primary functions of the testes are to produce sperm ( spermatogenesis ) and to produce androgens, primarily testosterone.
  • The functions of the testicle are influenced by gonadotropic hormones that are produced by the anterior pituitary.
  • Both testosterone and follicle-stimulating hormone are needed to support spermatogenesis.

Key Terms

  • gonad: A sex organ that produces gametes; specifically, the testes or ovaries.
  • testes: The male gonads responsible for the production of sperm and the secretion of testosterone.
  • ovaries: The female gonads responsible for the production of ova and the secretion of the key hormones
    estrogen and progesterone.

The gonad is the organ that makes gametes. The gonads in males are the testes and the gonads in females are the ovaries. Both gonads in males and females are endocrine glands.

The Ovaries

The ovary is a paired, ovum-producing, reproductive organ located in the lateral wall of the pelvis in a region called the ovarian fossa. The fossa usually lies beneath the external iliac artery and in front of the ureter and the internal iliac artery.

This is a cut-away illustration of a female (human) ovary. The blood supply for the human female reproductive organs is highlighted.

Ovary: Blood supply of the human female reproductive organs. The left ovary is visible above the label ovarian arteries.

The ovaries are not attached to the fallopian tubes but to the outer layer of the uterus via the ovarian ligaments. Usually each ovary takes turns releasing eggs every month; however, if there was a case where one ovary was absent or dysfunctional then the other ovary would continue providing eggs to be released.

Ovaries secrete both estrogen and progesterone. Estrogen is responsible for the development of the secondary sex characteristics of human females at puberty and for the maturation and maintenance of the reproductive organs in their mature functional state. Progesterone functions with estrogen by promoting menstrual cycle changes in the endometrium. The ovaries also secrete testosterone, although at a much lower level than in males.

Progesterone and estrogen are secreted by granulosal cells, whereas testosterone is produced by thecal cells. Prior to ovulation, follicle-stimulating hormone is secreted by the granulosal cells that convert testosterone into
estradiol.

The Testes

The testes are the male reproductive gonads in humans. Like the ovaries, to which they are homologous, testes are components of both the reproductive system and the endocrine system. The primary functions of the testes are to produce sperm (spermatogenesis) and androgens, primarily testosterone.

 

This is a schematic diagram of male (human) testicles.

Testicles: Diagram of male (human) testicles.

The functions of the testicles are influenced by gonadotropic hormones, that are produced by the anterior pituitary. Luteinizing hormone results in testosterone release. The presence of both testosterone and follicle-stimulating hormone is needed to support spermatogenesis. Testosterone is secreted by
Leydig cells, which are located between the
seminiferous tubules.

The testes are located in the scrotum (a sac of skin between the upper thighs). In the male fetus, the testes develop near the kidneys, then descend into the scrotum just before birth. Each testis is about 1 1/2 inches long by 1 inch wide.

Placenta

The placenta is an organ that connects the developing fetus to the mother’s blood supply.

Learning Objectives

Explain the role of the placenta in the endocrine system

Key Takeaways

Key Points

  • The placenta functions as a fetomaternal organ with two components: the fetal placenta and the maternal placenta.
  • The placenta connects to the fetus by an umbilical cord, which contains two arteries and one vein.
  • The perfusion of the intervillous spaces of the placenta with maternal blood allows the transfer of nutrients and oxygen from the mother to the fetus and the transfer of waste products and carbon dioxide back from the fetus to the maternal blood supply.
  • Waste products excreted from the fetus include: urea, uric acid, and creatinine, which are transferred to the maternal blood by diffusion across the placenta.
  • In humans, the placenta also secretes hormones ( human chorionic gonadotropin, human placental lactogen, estrogen, and progesterone ) that are important during pregnancy.

Key Terms

  • placenta: A vascular organ present only in the female during gestation. It supplies food and oxygen from the mother to the fetus, and passes back waste. It is implanted in the wall of the uterus and links to the fetus through the umbilical cord. It is expelled after birth.
  • umbilical cord: The flexible structure connecting a fetus with the placenta that transports nourishment to the fetus and removes waste.
  • human chorionic gonadotropin: A hormone produced during pregnancy that is made by the developing placenta after conception, and later by the placental component.

The placenta is an organ connecting the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother’s blood supply.

The placenta functions as a feto-maternal organ with two components:

  1. The fetal placenta, which develops from the same sperm and egg cells that form the fetus.
  2. The maternal placenta, which develops from the maternal uterine tissue.

In humans, the placenta averages 22 cm in length and 2–2.5 cm in thickness; it typically weights 500g and is a dark-reddish color due to the large quantities of blood contained within.

This is a schematic of a mother's womb. The fetus is seen connected to the placenta by the umbilical cord. The placenta is an organ connecting the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply.

Placenta: The placenta is an organ connecting the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother’s blood supply.

The placenta connects to the fetus by an umbilical cord of approximately 55–60 cm in length that contains two arteries and one vein. Unlike the majority of systemic vessels the arteries in the umbilical cord carry de-oxygenated blood and the vein  carries oxygenated blood.

The umbilical cord inserts into the chorionic plate of the placenta. Vessels branch out over the surface of the placenta and further divide to form a network covered by a thin layer of cells. This results in the formation of villous tree structures that allow for the efficient exchange of gasses and nutrients.

Functions of the Placenta

The major functions of the placenta include:

  • Nutrition
  • Excretion
  • Immunity and protection
  • Endocrine function

The perfusion of the intervillous spaces of the placenta with maternal blood allows the transfer of nutrients and oxygen from the mother to the fetus and the transfer of waste products and carbon dioxide back from the fetus to the maternal blood supply.

Waste products excreted from the fetus—urea, uric acid, and creatinine—are transferred to the maternal blood by diffusion across the placenta.

IgG antibodies can pass through the human placenta, thereby providing protection to the fetus in utero. The placenta functions as a selective maternal–fetal barrier against the transmission of microbes to the fetus. However, deficiency in this function may cause mother-to-child transmission of infectious diseases.

Endocrine Functions

The placenta also secretes hormones that are important during pregnancy. These hormones include:

  • Human chorionic gonadotropin
  • Human placental lactogen
  • Estrogen
  • Progesterone

Human chorionic gonadotropin (hCG) is the first placental hormone produced, which can be found in maternal blood and urine as early as the first missed menstrual period (shortly after implantation has occurred) through about the hundredth day of pregnancy.

This is the hormone analyzed by a pregnancy test; a false-negative result from a pregnancy test may be obtained before or after this period. Women’s blood serum will be completely negative for hCG by one to two weeks after birth. hCG testing is proof that all placental tissue is delivered. hCG is present only during pregnancy because it is secreted by the placenta, which is present only during pregnancy.

hCG also ensures that the corpus luteum continues to secrete progesterone and estrogen. Progesterone is very important during pregnancy because, when its secretion decreases, the endometrial lining will slough off and pregnancy will be lost. hCG suppresses the maternal immunologic response so the placenta is not rejected.

Human placental lactogen is lactogenic and promotes mammary gland growth in preparation for lactation in the mother. It also regulates maternal glucose, protein, and fat levels so they are always available to the fetus.

Estrogen stimulates the development of secondary female sex characteristics. It contributes to the woman’s mammary gland development in preparation for lactation and stimulates uterine growth to accommodate the growing fetus.

Progesterone is necessary to maintain the endometrial lining of the uterus during pregnancy. This hormone prevents pre-term labor by reducing myometrial contractions. Levels of progesterone are high during pregnancy.