Chapter 18 -2

Endocrine Glands

Comparison of neuronal and endocrine as communication channels

The neuronal system:

Has clear pathways which are connected with neurons. Thus it is reasonably clear for each neuron where it starts and where it ends.

At the end, knob, a neurotransmitters is released.

Its complexity makes it possible to stimulate more than one tissue and organs simultaneously.

The effect is relatively short lived.

Chemical Signals• Intercellular: Allow one cell to

communicate with other cells as hormones– Autocrine

• Released by cells and have a local effect on same cell type from which chemical signals released as prostaglandin

– Paracrine• Released by cells and affect other cell types locally

without being transported in blood as somatostatin

– Pheromones• Secreted into environment that modify behavior and

physiology as sex pheromones

Chemical Structure of Hormones

Control of Secretion Rate

• Most hormones are not secreted at constant rate• Patterns of regulation

– Involves action of substance other than hormone on an endocrine gland

– Involves neural control of endocrine gland– Involves control of secretory activity of one endocrine gland by

hormone or neurohormone secreted by another endocrine gland

3. Control of secretion rate

In essence the control is in a form of negative feedback. Three major patterns:

a. By other substance; Such as sugar control the regulation of insulin

release. Increased blood sugarStimulates insulin release from the pancreasInsulin stimulates glucose uptake by

tissuesResults in decreased blood sugar

There are three major types of hormone structures: (Table 17.2 and Fig. 17.3)

i. Amino acid derivatives: Epinephrine, Norepinephrine, the thyroid

hormones, pineal hormone (melatonin)

ii. Peptide/protein hormone: Antidiuretic hormone, glucagon, oxytocin,

growth hormone, prolactin, insulin.

iii. Lipid derivatives:

a. Steroid hormones. Estrogens, testosterone,

b. Prostaglandins. Derived from arachidonic acid.

REVIEW of the mechanisms of hormonal action

The action of hormone is usually by activation of cytosolic enzymes or DNA.

But, first, the hormones identify the target cells by the receptors on the membrane (epinephrine, Norepinephrine, peptide hormones) or in the cytoplasm (steroid hormones) or the nucleus (thyroid hormones).

The hormones which attack the target receptors on the membrane do not usually permeate through the membrane. These are first messengers.

The first messenger binds the receptor on the membrane and triggers the release of the second messenger.

Hormone - receptor - release of cyclic AMP - activation of adenylate cyclase - ATP becomes cyclic-AMP

Cyclic-AMP can activate enzymes specific to a cell.

Thus, one hormone can have effect on many different types of cells.

Other second messengers are Ca++ and cyclic-GMP.

Thyroid and steroid hormones have effects directly on the nucleus or indirectly through cytosol.

These hormones affect protein synthesis e.g. anabolic steroid hormone.

Control of endocrine activity

The regulation of endocrine activity with the hypothalamus is a good example of how the nervous system and endocrine system integrate (Fig. 18-5).

In addition, the activity of endocrine cells may be in response to its environment by negative feedback.

For example:

If circulating Ca++ levels go down - Parathyroid hormone is released - Target cell elevates Ca++ level - Increased Ca++ level - Releases Calcitonin - lowered Ca++ level

Always prepare to ask:

Where is the gland found?How does it look like?What stimulates the gland?What hormone does it release?What is the target organ(s)?Ultimately, what does it do?

Endocrine System Functions

• Metabolism and tissue maturation• Ion regulation• Water balance• Immune system regulation• Heart rate and blood pressure regulation• Control of blood glucose and other nutrients• Control of reproductive functions• Uterine contractions and milk release

Pituitary Gland and HypothalamusNote the direction of the face

• Where nervous and endocrine systems interact

• Pituitary gland/hypophysis– Secretes 9 major hormones

• Hypothalamus– Regulates secretory activity

of pituitary gland through neurohormones and action potentials

– Posterior pituitary is an extension of the hypothalamus

Pituitary Gland Structure• Posterior or neurohypophysis

– Continuous with the brain– Secretes neurohormones

• Anterior or adenohypophysis– Consists of three areas with indistinct boundaries: pars

distalis, pars intermedia, pars tuberalis

This small hypophysis (pituitary gland): (Fig. 18-6) is located under the hypothalamus, excretes 9 major peptide hormones which are regulated by hypothalamus and exhibits profound effects on many tissue and organs.

a. The Structure

I cm in diameter0.5 - 1gSits on the sella turcica of the sphenoid boneConnected to hypothalamus through infundibulum.

Divided into Posterior pituitary (neurohypophysis)Anterior pituitary (adenohypophysis)

b. Posterior Pituitary

Developmentally, it is an extension of the brainReleases neurohormones

c. Anterior Pituitary

Developmentally, traces back to the oral cavity called Rathke’s pouch.Divided into three distinctive areas:The pars tuberalisThe pars distalisThe pars intermediaReleases endocrine hormones

d. Regulation of pituitary by hypothalamus

i. The anterior pituitary (Fig. 18-7)

In the region pituitary connects with hypothalamus and anterior pituitary, there are two capillary networks:

Hypothalamohypophyseal portal system as the primary capillary networkSecondary capillary network in anterior pituitary.

Neurohormones released from hypothalamus enter the primary capillary.

The hormones carried to the secondary capillary and released into anterior pituitary.

These hormones may either increase or inhibit the excretion of hormones from the anterior pituitary.

Hormones from the anterior pituitary, then will be carried by the circulatory system.

Note the number of neurohormones released from the hypothalamus that affect the anterior pituitary gland. (Fig. 18-8a,b) Most of them are small peptides

ii. The posterior pituitary (Fig 18-7)

As for the posterior pituitary, there is no connecting portal system.

The neurosecretory cells from the hypothalamus extend to the posterior pituitary through hypothalamohypophyseal tract.

The neurohormones will be released into the portal system of the posterior pituitary.

Hypothalamus, Posterior Pituitary Gland

Pituitary Gland HormonesMostly peptides, proteins or glycoproteins.

• Posterior– Antidiuretic hormone

(ADH)

– Oxytocin

• Anterior– Growth hormone (GH) or

somatotropin– Thyroid-stimulating

hormone (TSH)– Adrenocorticotropic

hormone (ACTH)– Melanocyte-stimulating

hormone (MSH)– Luteinizing hormone (LH)– Follicle-stimulating

hormone (FSH)– Prolactin

Anterior Pituitary Hormones

Hormone secretion is regulated by the neurohormones from the hypothalamus.

Growth hormone GH (protein): Targets many cells and over all increase in metabolism. Control of GH secretion is shown in Seeley’s Fig. 18.6.

Growth Hormone (GH)

• Stimulates uptake of amino acids and conversion into proteins

• Stimulates breakdown of fats and glycogen

• Promotes bone and cartilage growth

• Increased secretion in response to increase amino acids, low blood glucose, or stress

• Regulated by GHRH and GHIH or somatostatin

Thyroid-stimulating hormone TSH (glycoprotein): Targets the thyroid gland and increase thyroid hormone release

Adrenocorticotropic hormone ACTH (peptide): Targets the adrenal cortex and increase glucocorticoid hormone secretion.

These hormone, which stimulate release of hormones from other endocrine glands are called “tropic hormones”

The gonadotropins include follicle-stimulating hormone, luteinizing hormone and prolactin and regulate activity of gonads. They are under regulation of gonadotropin releasing hormone (GnRH) from the hypothalamus.

Follicle-stimulating hormone promotes follicle development in females and together with LH stimulates release of estrogens. In males FSH stimulates sustentacular cell formation. FSH production is inhibited by inhibin.

Luteinizing hormone induces ovulation, promotes secretion of the estrogens and the progesterone. More later.

Prolactin stimulates mammary gland development, milk production.

ii. Posterior Pituitary Hormones

The posterior pituitary stores and releases two polypeptide neurohormones formed in the hypothalamus and transmitted through hypothalamohypophyseal nerve tract:

Antidiuretic hormone (ADH): prevents production of large quantity of urine. It is also vasopressin and constricts blood vessels. Control of ADH secretion is shown in Seeley’s Fig. 18.5.

Oxytocin: stimulates the smooth muscle cells of the uterus. Important for expulsion of the fetus. Milk ejection.

Question: Does the posterior pituitary gland make its own hormone?

Antidiuretic Hormone

• Also called vasopressin• Promotes water retention by kidneys• Secretion rate changes in response to alterations in blood

osmolality and blood volume• Lack of ADH secretion is a cause of diabetes insipidus

Oxytocin

• Promotes uterine contractions during delivery

• Causes milk ejection in lactating women

Thyroid Gland

• One of largest endocrine glands

• Highly vascular

• Histology– Composed of follicles

– Parafollicular cells• Secrete calcitonin which

reduces calcium concentration in body fluids when levels elevated

Hormones of the thyroid

The follicular cells of the thyroid gland (Fig. 18-12) release derivatives of tyrosine to which three or four iodine molecules are attached, thus

triiodothyronine (T3)-10%tetraiodothyronine (T4)-90% - thyroxine.

Parafollicular cells (Fig. 18.7b,c) release calcitonin.

Thyroid Hormones

• Include– Triiodothryronine or T3

– Tetraiodothyronine or T4 or thyroxine

• Transported in blood

• Bind with intracellular receptor molecules and initiate new protein synthesis

• Increase rate of glucose, fat, protein metabolism in many tissues thus increasing body temperature

• Normal growth of many tissues dependent on

Synthesis of T3 and T4

Thyroid hormone synthesis requires thyroid stimulating hormone (TSH) from the anterior pituitary and iodine. (Fig. 18-12a)

Secretion of thyroid hormone is initiated by TSH. (Fig. 18-12b and Seeley Fig. 18.9.)

In fact, it starts with a release of TRH from the hypothalamus, to the hypothalamohypophyseal portal system of the anterior pituitary, where TSH is released. TSH reaches the thyroid gland through the circulatory system and regulate the secretion of T3 and T4.

Regulation of T3 and T4 Secretion

Transporting thyroid hormones

Thyroid hormones are transported through the circulatory system bound with thyroxin-binding globulin (TBG) The binding helps the half-life of the hormones to increase to 1 week in the circulatory system. During this period thyroxin (T4) may convert to T3, which is the more active form

f. The targets of thyroid hormones

Thyroid hormones affect many cells, but not exactly in the same manner. They affect metabolism, growth and maturation.

They permeate through the membrane and bind with the receptors in the nuclei to react with the DNA for protein synthesis.

Thyroid hormone may interact with mitochondria and produce more ATP and hence heat production.

It requires about 1 week for the thyroid hormones to take effect.

Thyroid Hormone Hyposecretion and

Hypersecretion• Hypothyroidism

– Decreased metabolic rate

– Weight gain, reduced appetite

– Dry and cold skin

– Weak, flabby skeletal muscles, sluggish

– Myxedema

– Apathetic, somnolent

– Coarse hair, rough dry skin

– Decreased iodide uptake

– Possible goiter

• Hyperthyroidism– Increased metabolic rate

– Weight loss, increased appetite

– Warm flushed skin

– Weak muscles that exhibit tremors

– Exophthalmos

– Hyperactivity, insomnia

– Soft smooth hair and skin

– Increased iodide uptake

– Almost always develops goiter

Parafollicular cells and Calcitonin

Increased level of Ca++ stimulates the release of calcitonin from the Parafollicular cells.

The target is bone tissue and decreases osteoclast activity, thus increases the life span of osteoblasts.

Thus decreases blood Ca++ and phosphates.

Therefore, blood calcium level may be regulated with calcitonin.

Parathyroid Glands

• Embedded in thyroid • Secrete PTH

– Increases blood calcium levels

– Stimulates osteoclasts

– Promotes calcium reabsorption by kidneys

c. Targets and Function

Parathyroid hormone (PTH) regulates calcium levels and targeted to bone, the kidneys and the intestine.

The action is opposite to calcitonin

PTH stimulates, for exampleOsteoclast activity in bone tissue leading to bone resorption and the release of calcium and phosphate, i.e. increased blood Ca++ (,but not necessarily phosphate). Induces Ca++ reabsorption in the kidneys to increase enzyme activity to form vitamin D.

Inactive parathyroid glands, due to lack of Ca++ increase in blood by PTH, lead to hypocalcemia - nervousness, spasm, etc.

Adrenal Glands

• Functions as part of sympathetic nervous system• Composed of medulla and cortex (3 layers)• Hormones

– Medulla secretes epinephrine and norepinephrine– Cortex secretes mineralocorticoids, glucocorticoids, androgens

Hormones of Adrenal Cortex• Mineralocorticoids

– Zona glomerulosa– Aldosterone produced in greatest amounts

• Increases rate of sodium reabsorption by kidneys increasing sodium blood levels

• Glucocorticoids– Zona fasciculata– Cortisol is major hormone

• Increases fat and protein breakdown, increases glucose synthesis, decreases inflammatory response

• Androgens– Zona reticularis– Converted to androgen and testosterone

Pancreas

• Located along small intestine and stomach

• Exocrine gland– Produces pancreatic digestive

juices

• Endocrine gland– Consists of pancreatic islets– Composed of

• Alpha cells secrete glucagon• Beta cells secrete insulin• Delta cells secrete

somatostatin

The exocrine portion consists of Acini that produces pancreatic juice (enzymes) and a duct system.

The endocrine part consists of pancreatic islets (islets of Langerhans) separated into:

Alpha cells (glucagon production, protein)Beta cells (insulin production, polypeptide).Delta cells (somatostatin, peptide)F Cells (pancreatic polypeptide PP)

c. Hormones of the pancreas (Table 18-6)

Insulin is a protein, glucagon is a polypeptide, and somatostatin is a peptide.

i. Insulin

Produced in beta cells in response to rising blood glucose and amino acids. Targets the liver, adipose tissue, muscles the hypothalamus.

Insulin binds to the receptor on the membrane and stimulates glucose transport into the cells. Glucose, once inside the cell, is metabolized to make energy, glycogen, amino acids, proteins, fats, etc.

Glucose uptake by the kidneys, lining of digestive tracts, red blood cells and brain cells is independent of insulin.

ii. Glucagon

Secreted from alpha cells when blood glucose levels fall.

In the liver, it stimulates glycogenolysis (glycogen hydrolysis) and releases glucose into circulation..

In adipose tissue it initiates breaking down of fats and releases free fatty acids and ketone bodies.

It also responds to blood amino acids after high protein meal.

iii. Somatostatin

Produced in delta cells of islets when blood glucose and amino acids rise after a meal.

It behaves as a paracrine secretion (chemical messenger that diffuses to neighboring target cells, i. e. alpha and beta cells.).

Thus modulates their activities.

Insulin and Glucagon

Insulin• Target tissues: liver,

adipose tissue, muscle, and satiety center of hypothalamus

• Increases uptake of glucose and amino acids by cells

Glucagon• Target tissue is liver• Causes breakdown of

glycogen and fats for energy

Regulation of Blood Nutrient Levels After a Meal

Regulation of Blood Nutrient Levels During Exercise

Hormones of the Reproductive System - more later

Male: Testes

• Testosterone– Regulates production of

sperm cells and development and maintenance of male reproductive organs and secondary sex characteristics

• Inhibin– Inhibits FSH secretion

Female: Ovaries• Estrogen and Progesterone

– Uterine and mammary gland development and function, external genitalia structure, secondary sex characteristics, menstrual cycle

• Inhibin– Inhibits FSH secretion

• Relaxin– Increases flexibility of

symphysis pubis

Pineal Body

• In epithalamus• Produces

– Melatonin• Enhances sleep

– Arginine vasotocin• Regulates function of

reproductive system in some animals

b. The kidneys

The kidneys release the steroid hormone calcitriol, the peptide hormone erythropoietin and the enzyme rennin.

Erythropoietin

Released from kidney when oxygen level is low.

Simulate synthesis of erythrocytes in the bone marrow.

Calcitriol

In response to PTH, cholecalciferol (Vitamin D3) is formed in the skin under the sun and eventually becomes calcitriol. Calcitriol stimulates calcium and phosphate absorption, stimulates Ca++ release from bone, and inhibits PTH secretion. See Fig. 18-20 and Table 18-7 for details.

Renin

Response to the loss in renal blood flow rein-angiotensin system is activated (See Fig. 18-20b)

Effects of Aging on Endocrine System

• Gradual decrease in secretory activity of some glands– GH as people age– Melatonin– Thyroid hormones– Kidneys secrete less renin

• Familial tendency to develop type II diabetes

Diabetes Mellitus

• Results from inadequate secretion of insulin or inability of tissues to respond to insulin

• Types– Type I or IDDM (Insulin-dependent)

• Develops in young people

– Type II or NIDDM (Non-insulin dependent)• Develops in people older than 40-45

• More common

Patients with Diabetes Mellitus have difficulty in controlling their blood sugar level. The causes are attributed to:

Inability to make insulin by the pancreatic islet cells – Type I, IDDM

Lack of membrane receptor for insulin on the cells of target tissues. – Type II,

NIDDM

1. The first type is called insulin dependent diabetes mellitus (IDDM), since the patients may be treated with insulin, or Type I diabetes.

It accounts for about 3% of the total diabetes population.

It is assumed that the cause is related to the loss of insulin production by pancreatic islets, possibly due to an auto-immune disease.

The patients are primarily children.

2. The second type is called non-insulin dependent diabetes mellitus (NIDDM), since insulin does not improve the condition of the patients, or Type II diabetes.

It accounts for 97% of the total diabetes population.

The target cells of insulin appear to have diminished ability to produce insulin receptors, thus the effect of insulin is declined.

The patients are mostly adult and sometime the disease is referred to as adult on set diabetes.

Genetic linkage is suspected.

In addition to glucose tolerant test and others, chronic severity of the disease may be assessed by the level of HbAIC, which is a glucose bound (glycated) hemoglobin.

Glucose binds to hemoglobin spontaneously and the degree of bound glucose is proportional to the level of blood glucose, since glucose permeates the membrane of red blood cells almost freely.

Thus, the higher the concentration of blood glucose the higher the percentage of HbAIC The value could go as high as 15% compared with 2-3% of the normal subject.