Lecture 5: Endocrine System

General hormones are the hormones released by the endocrine system. They are released into the body fluids, the blood, and may affect many cell types in a tissue and body fluids.

Exocrine glands include sweat, oil, mucous, and digestive glands. Endocrine glands release hormones directly into body fluids. The pancreas acts as both exocrine and endocrine gland. The effects of of the endocrine system tend to be slower, less direct, and longer lasting than those of the nervous system.

All hormones act by binding to proteins called receptors. Each receptor is highly specific for its hormone. The effects of the endocrine system are to alter metabolic activities, regulate growth and development, and guide reproduction. Many endocrine glands are stimulated by neurons to secrete their hormones.

Hormones exist in three basic chemistry types: 1) peptide hormones 2) steroid hormones 3) tyrosine derivatives

Peptide Hormones are derived from peptides. All peptide hormones are manufactured in the rough ER. Peptide hormones are water soluble, and thuse move freely through the blood, but have difficulty diffusing through the cell membrane of the effector. The effector is the target cell of the hormone; the cell the hormone is meant to affect. Instead of diffusing through the membrane, peptide hormones attach to a membrane-bound receptor. The receptor may itself act as an ion channel increasing membrane permeability to a specific ion, or the receptor may activate or deactivate other intrinsic membrane proteins also acting as ion channels.

Another effect of the hormone binding to the receptor is to activate an intracellular second mesenger such as cAMP or cGMP. The second messenger activates or deactivates enzymes and or ion channels and often creates a cascasde of chemical reactions that amplifies the effect of the hormone.

List of Peptide Hormones:

the anterior pituitary hormones: FSH, LH, ACTH, hGH, TSH, Prolactin

the posterior pituitary hormones: ADH and oxytocin

the parathyroid hormone: PTH

the pancreatic hormones: glucagon and insulin

Steroid Hormones: are often chemically similar to cholestrol. They are formed in the smooth ER and the mitochondria. Since they are lipids, steroids typically require a protein transport molecule in order to dissolve into the blood stream. Steroids diffuse through the cell membrane of their effector. Once inside the cell, they combine with a receptor in the cytosol. The receptor transports the steroid into the nucleus, and the steroid acts at the transcription level.

List of important steroid hormones:

the glucocorticoids and mineral corticoids of the adrenal cortex: cortisol and aldosterone

the gonadal hormones: estrogen, progesterone, testosterone

The tyrosine derivatives are: the thyroid hormones T3, T4 and the catecholamines formed in the adrenal medulla: epinephrine and norepinephrine. All tyrosine derivative hormones are formed by enzymes in the cytosol or on the rough ER.

Thyroid hormones are lipid soluble and must be carried in the blood by plasma protein carriers. They then bind to receptors inside the nucleus. Their high affinity to their binding proteins in the plasma and in the nucleus create a latent period in their response and increase the duration of the effect of thyroid hormones. Epinephrine and norepinephrine are water soluble.

The control point of the feedback is the conduct of the effector, not the concentration of hormone. The gland lags behind the effector.

For instance, high insulin levels do not typically create low blood glucose. Instead high insulin levels are caused by high blood glucose, and low blood glucose would cause high blood glucagon levels.

A given gland produces one of either steroids, peptides, or tyrosine derivatives, but not two.

The thyroid secretes T3 and T4, which are tyrosine derivatives, and calcitonin, which is a peptide.

The anterior pituitary is located in the brain beneath the hypothalamus. The hypothalamus controls the release of the anterior pituitary hormones with releasing and inhibitory hormones of its own. The release of the releasing and inhibitory hormones is, in turn, controlled by nervous signals throughout the nervous system.

• hGH
• Human growth hormone, a peptide, stimulates growth in almost all cells of the body. hGH stimulates growth by increasing episodes of mitosis, increasing cell size, increasing the rate of protein synthesis, mobilizing fat stores, increasing the use of fatty acids for energy, and decreasing the use of glucose.

• ACTH
• ACTH, a peptide, stimulates the adrenal cortex to release glucocorticoids via the second messenger system using cAMP. Glucocorticoids are stress hormones.

• TSH
• TSH, a peptide, stimulates the thyroid to release T3 and T4 via the second messenger system using cAMP. TSH increases thyroid cell size, number, and the rate of secretion of T3 and T4. T3 and T4 have a negative feedback effect on TSH.

• Prolactin
• Prolactin, a peptide, promotes lactation. The hypothalamus inhibits the release of prolactin. The act of suckling, which stimulates the hypothalamus to stimulate the anterior pituitary to relase prolactin, inhibits the mentrual cycle.

The posterior pituitary is composed mainly of support tissue for nerve endings extending from the hypothalamus. Both oxytocin and ADH are small polypeptides.

Oxytocin is a small peptide hormone that increases uterine contractions during pregnancy and causes milk to be ejected from the breasts.

ADH (vasopressin) is a small peptide hormone which causes the collecting ducts of the kidney to become permeable to water reducing the amount of urine and concentrating the urine. ADH also increases blood pressure. Coffee and beer are ADH blockers that increase urine volume.

The adrenal glands are located on top of the kidneys. The adrenal cortex is the outside portion of the gland. The cortex secretes only steroid hormones. There are two types of steroid secreted by the cortex:mineral corticoids and glucocorticoids. Mineral corticoids affect the electrolyte balance in the blood stream; glucocorticoids increase blood glucose concentration and have an even greater effect on fat and protein metabolism.

• Aldosterone
• Aldosterone, a steroid, is a mineral corticoid that acts in the distal convoluted tubule and the collecting dust to increase Na+ and Cl- reabsorption and K+ and H+ secretion. The result is in increase in blood pressure. The main main effect is Na+ reabsorption and K+ secretion in the collecting tubule of the kidney.

• Cortisol
• Cortisol, a steroid, is a gluccocorticoid that increases blood glucose levels by stimulating gluconeogenesis in the liver. Cortisol also degrades adipose tissue to fatty acids to be used for cellular energy. Cortisol is a stress hormone. The beneift of excess cortisol under stressful situations is not full understood.

• Catecholamines
• The catecholamines are the tyrosine derivatives synthesized in the adrenal medulla:epinephrine and norepinephrine. Both are vasoconstrictors which is consistent with the fight or flight response of these hormones. These are stress hormones.

T3 and T4 are very similar in effect. T3 contains three iodine atoms, and T4 contains four. Their general effect is to increase the basal metabolic rate. Thyroid hormone secretion is regulated by TSH.

• Calcitonin
• Calcitonin is a large peptide hormone released by the thyroid gland. It slightly decreases blood calcium by decreasing osteoclast activity and number.

• Insulin
• Insulin, a peptide hormone, is releasd by the B-cells of the pancreas. It is associated with energy abundance in the form of high energy nutrients in the blood. Insulin is released when blood levels of carbohydrates or proteins are high. In the presence of insulin, carbohydrates are stored as glycogen in the liver and muscles, fat is stored in adipose tissue, and amino acids are taken up by the cells of the body and made into proteins. The effect of insulin is to lower blood glucose levels. The cells of the body become highly permeable to glucose upond the binding of insulin.

• Glucagon
• Glucagon, a peptide hormone, is released by the a-cells of the pancreas. Glucagon stimulates glycogenolysis (the breakdown of glycogen), and gluconeogenesis in the liver. It acts via the second messenger system of cAMP. In high concentrations, glucagon breaks down adipose tissue increasing the fatty acid level in the blood. The net effect of glucagons is to raise blood glucose levels.

There are four small parathyroid glands which release the parathyroid hormone.

• PTH
• Parathyroid hormone, peptide, increases blood calcium. PTH increases renal calcium reabsorption and renal phosphate excretion.

The male gonads are called the testes. Production of sperm occurs in the seminiferous tubules of the testes. Spermatogonia located in the seminiferous tubules arise from epithelial tissue to become spermatocytes, spermatids, and then spermatozoa. LH stimulates testosterone. Testosterone is the primary androgen (male sex hormone), and stimulates the germ cells to become sperm. Testosterone is also responsible for the development of secondary sex characteristics such as pubic hair, enlargement of the larynx, and growth of the penis and seminal vesicles.

The spermatozoon is carried to the epididymus to mature. Upon ejaculation, spermatozoa are propelled through the vas deferens into the urethra and out of the penis. Semen is the complete mixture of spermatozoa and fluid that leaves the penis upon ejaculation. Semen is composed of fluid called Cowper's glands.

Oogenesis begins in the ovaries of the fetus. At puberty, FSH stimulates the growth of granulosa cells around the primary oocyte. The granulosa cells secrete a viscuous substance around the egg called the zona pellucida.

Upon stimulation by LH, theca cells secrete androgen, which is conveted to estradiol (a type of estrogen) by the granulosa cells in the presence of FSH and secreted into the blood. The estradiol is a steroid hormone that prepares the uterine wall for pregnancy. Just before ovulation (the bursting of the follicle), the estradiol level rises rapidly, actually causing a dramatic increase in LH secretion. This increase is called the luteal surge. The luteal surge results from a positive feedback loop of rising estrogen levels which increase LH levels, which increase estrogen.

The egg is swept into the fallopian tube or oviduct. The remaining portion of the follicle is left behind to become the corpus luteum. The cycle just described repeats itself every 28 days after puberty unless pregnancy occurs. This is called the menstrual cycle.

1) the follicular phase, which begins the development of the follicle

2) the luteal phase, begins with ovulation and ends with the degeneration of the corpus liteum into the corpus albicans.

3) flow, which is the shedding of the uterine lining lasting apporximately 5 days.

Once in the fallopian tube, the egg is swept toward the uterus by cilia. Fertilization normally takes place in the Fallopian tubes. The enzymes of the acrosome in the sperm are released upon contact with the egg, and digest a path for the sperm through the granulosa cells. The sperm nucleus enters the cytoplasm of the oocyte. The entry of the sperm causes cortical reaction, which prevents other sperms from fertilizing the same egg. Now the oocyte goes through the second meiotic division to become an ovum and releases a second polar body. Fertilization occurs when the nuclei of the ovum and sperm fuse to form the zygote.

Cleavage begins while the zygote is still in the Fallopian tube. When the zygote is comprised of eight or more cells, it is called a morula. The first eight cells formed by cleavage are equivalent in size and shape and are said to be totipotent, meaning they have the potential to express any of their genes. The cells of the morula continue to divide for four days forming a hollow ball filled with fluid. This fluid ball is called a blastocyst. It is the blastocyst that lodges in the uterus in a process called implantation on about the 5th or 7th day after ovulation. Upon implantation, a female is said to be pregnant.

Upon implantation, the egg begins secreting a peptide hormone called human chorionic gonadotropin (HGC). HGC prevents the degenration of the corpus luteum, and maintains its secretion of estrogen and progesterone. HCG in the blood and urine of the mother is the first outward sign of pregnancy. A placenta is formed from the tissue of the egg and the mother, and takes over the job of hormone secretion. The placenta reaches full development by the end of the 3rd triemster and begins secreting its own estrogen and progesterone while lowering its secretion of HCG.

The process where a cell becomes committed to a specialized developmental path is called determination. The specialization that occurs at the end of the developmental forming a specialized tissue cell is called differentation.

The formation of the gastrula occurs in the 2nd week after fertilization in a process called gastrulation. During gastrulation, the three primary germ layers are formed 1) ectoderm 2) mesoderm 3) endoderm

The ectoderm cells develop into the outter covering of the body, such as the skin, nails, and tooth enamel, and into the cells of the nervous system and sense organs.

The endodermal cells develop into the lining of the digestive tract, and into much of the liver and pancreas.

The mesoderm is the stuff that lies between the inner and outer covering, muscle, bone.

In the 3rd week, the gastrula develops into a neurola in a process called neurolation. The notochord induces the overlying ectoderm to thicken and form the neural plate. Induction occurs when one cell type affects the direction of diffentiation of another cell type.

Part of normal cell development is programmed cell death or apoptosis. Apoptosis is essential for development of the nervous system, operation of the immune system, and destruction of tissue between fingers and toes to create normal hands. Mitochondria play a role in apoptosis.