THE ENDOCRINE SYSTEM
A. ENDOCRINE GLANDS
Compare exocrine with endocrine glands.
The body contains two types of glands:
Exocrine glands secrete their products into ducts or directly onto
epithelial surfaces.
Endocrine glands secrete their products called hormones, into the extracellular fluid around the secretory cells. The secretion then diffuses into the blood for distribution throughout the body.
Which organs are endocrine only?
There are a number of specific organs whose sole function is endocrine:
pituitary gland
thyroid gland
parathyroid glands (4)
adrenal glands (2)
pineal (epithalamus)
thymus gland
Name other organs that have some endocrine function.
pancreas
gonads (2)
kidneys
stomach
small intestine
liver
heart
placenta
B. COMPARISON OF NERVOUS AND ENDOCRINE SYSTEMS
Together, the nervous and endocrine systems coordinate the functions of all body systems. How does the nervous system achieve this?
The nervous system achieves this through the use of nerve impulses and the secretion of neurotransmitter substances that either excite or inhibit the effector.
How does the endocrine system achieve this control?
The endocrine system, in contrast, regulates body functions by releasing chemical messengers called hormones (“to urge on” or “to set in motion”) into the bloodstream for delivery throughout the body.
Compare the types of effectors the two systems utilize to maintain homeostasis.
The nervous system causes muscles to contract and glands to secrete. The endocrine system regulates metabolic activities, growth and development, and reproduction.
Compare the time frame the two systems need to accomplish their actions.
The nervous system tends to act in milliseconds. The endocrine system acts in seconds, minutes, hours, weeks, months, even years, depending upon the hormone.
Compare how long the effects of the two systems persist.
Nervous effects are brief; endocrine effects are much longer lasting.
C. HORMONES
1. HORMONE RECEPTORS
What is an endocrine target cell?
Although a given hormone travels throughout the body in the blood and is “seen” by all cells of the body, it only affects specific cells called target cells.
Like neurotransmitters, hormones influence their target cells by chemically combining to protein receptors on the target cell surface.
Only target cells for a particular hormone bear receptors for that hormone, bind to it, and respond to it.
Receptors, like other cellular proteins, are constantly synthesized and broken down as part of routine cellular maintenance.
What is down-regulation of a target cell’s hormone receptors?
Down-regulation occurs when the hormone is present in excess
and the cell reduces the number of available receptors for it. This causes a decrease in cellular responsiveness to the hormone.
What is up-regulation of a target cell’s hormone receptors?
Up-regulation occurs when the hormone is present in less than
normal amounts and the cell increases the number of available receptors for it. This causes an increase in cellular responsiveness to the hormone.
2. CIRCULATING AND LOCAL HORMONES
Define each of the following:
Circulating hormones – Hormones that pass into the blood and act
on distant target cells are called circulating hormones or endocrines.
Local hormones – Hormones that act on target cells close to their
site of release are called local hormones. They are further subdivided into either paracrine or autocrine.
Paracrine hormones – Paracrines are local hormones that act on
neighboring cells.
Autocrine hormones – Autocrines are local hormones that act on
the same cell that secreted them.
D. MECHANISMS OF HORMONE ACTION
Various target cells may respond differently to the same hormone (Ex: insulin in the liver causes glycogen formation, but in adipose cells it causes lipid formation). Give a brief discussion for how this is possible.
The response of a target cell to a hormone depends on both the hormone and the target cell. In part, these varied effects of hormones are possible because there are different mechanisms of hormone action. Hormones bind to and activate their specific receptors in different ways.
Where are the receptors for lipid-soluble hormones?
Lipid-soluble hormones, which can diffuse freely through the cell membrane, use target cell receptors that are found in the cytoplasm or nucleus of target cells.
Where are the receptors for water-soluble hormones?
Water-soluble hormones, which cannot cross the cell membrane, use target cell receptors, integral proteins found on the cell surface of target cells.
1. ACTIVATION OF INTRACELLULAR RECEPTORS
Name the lipid-soluble hormones and give a brief description of their mechanism of action at the target cell.
Steroid hormones and thyroid hormones are lipid-soluble and easily pass through cell membranes.
Upon entering a target cell, the hormone binds to and activates an intracellular receptor, located within the nucleus.
The activated hormone-receptor complex than alters gene expression by turning specific genes of the nuclear DNA either on or off.
This usually involves the synthesis of new enzymes that alter cellular metabolism in the way specific for that hormone, and in that way alters some function.
2. ACTIVATION OF PLASMA MEMBRANE RECEPTORS
Name the water-soluble hormone and give a brief description of their mechanism of action at the target cell.
Catecholamine, peptide, and protein hormones are water-soluble,
cannot diffuse through the cell membrane, and therefore must utilize receptors on the target cell surface.
Since the hormone can only bring the physiological message to the cell membrane of the target cell, rather than the nucleus, the hormone is called the first messenger.
A second messenger is needed to relay the message from the receptor, through the cell membrane, and into the cytoplasm where the hormone-stimulated response can take place.
The best known second messenger is cyclic 3’, 5’-monophosphate (cyclic AMP or camp).
The receptor is attached on its inner side to the enzyme adenylate cyclase. The enzyme is stimulated to convert intracellular ATP to cyclic AMP when the hormone binds to the receptor.
Increased levels of intracellular cyclic AMP acts as a second messenger within the cell, directing a specific response that is cell-type dependent.
The increased cyclic AMP within the cell is transient, however, because of the intracellular enzyme phosphodiesterase, which quickly degrades cyclic AMP to 5’-AMP.
5’-AMP has no biological activity (therefore, the hormonal effect on the cell is tightly regulated) within the cell and is used to regenerate ATP.
E. CONTROL OF HORMONAL SECRETIONS
In general, how are hormone secretions controlled?
Most endocrine glands secrete their product(s) in short bursts, with little or no secretion in between stimulations.
Regulation of secretion depends on homeostasis and prevents over- or underproduction.
Hormone secretion is stimulated and inhibited by signals from the nervous system, chemical changes in the blood, and other hormones.
Most often, negative feedback systems maintain homeostasis for hormonal secretions.
F. HYPOTHALAMUS AND PITUITARY GLAND (HYPOPHYSIS)
What is the role of the hypothalamus in endocrine control?
The hypothalamus serves as the master control for many of the hormones secreted by the endocrine system, and serves as the major integrator between the nervous and endocrine systems. In particular, the hypothalamus controls the secretions of the pituitary gland, also known as the hypophysis.
What is the anatomical relationship between the pituitary gland and the hypothalamus?
The pituitary gland is a pea-sized organ lying within the sella turcica of the sphenoid bone. It is suspended from the base of the hypothalamus by the infundibulum, a stalk-like structure.
Describe the pituitary gland by describing its embryologic formation.
The pituitary gland has two anatomically and functionally distinct portions due to its embryological formation.
The anterior pituitary gland (adenohypophysis) (about 75% of the total gland) is derived from an outpouching of the roof of the developing mouth, called Rathke’s pouch.
Rathke’s pouch breaks off from the mouth and migrates as a unit to make contact with the forming posterior pituitary gland associated with the hypothalamus.
The posterior pituitary gland (neurohypophysis) forms as an outgrowth of the base of the hypothalamus and remains attached to it via the infundibulum.
The posterior pituitary gland contains axons and axon terminals of about 5,000 neurons whose cell bodies are located in nuclei in the hypothalamus.
The nerve fibers that terminate in the posterior pituitary gland are associated with neuroglial-like support cells called pituicytes, which are secretory.
Regardless of origin, both the anterior and posterior pituitary glands are wholly dependent upon the hypothalamus for regulation of hormonal secretion.
Describe the anatomical mechanism by which the hypothalamus controls hormonal secretions from the anterior pituitary gland.
The anatomical pituitary gland (adenohypophysis) secretes seven hormones that regulate a wide variety of bodily functions.
Release of these hormones is dependent upon chemicals secreted by the hypothalamus called releasing and inhibiting factors (hormones).
These hypothalamic hormones reach the anterior pituitary gland through a system of blood vessels that connect the two regions.
This system of vessels, called the hypophyseal portal system, consists of several superior hypophyseal arteries that enter the lower hypothalamic region and divide into the primary plexus of capillaries.
The primary plexus is recollected into hypophyseal veins that pass down the infundibulum, enter the anterior pituitary gland, then divide into the secondary plexus of capillaries.
The secondary plexus is then recollected into the anterior hypophyseal veins that exit the anterior pituitary gland and return the blood to the general circulation.
The releasing and inhibiting factors secreted by hypothalamic neurons diffuse into the blood of the primary plexus and are carried by the portal system into the anterior pituitary.
The factors diffuse out of the blood of the secondary plexus and into the interstitial fluid of the anterior pituitary, where they interact with their specific target cells.
In response, the cells of the anterior pituitary may secrete specific hormones that diffuse into the blood of the secondary plexus and ultimately are distributed throughout the body.
1. ANTERIOR PITUITARY GLAND (ADENOHYPOPHYSIS)
Name the seven hormones secreted by the anterior pituitary gland.
growth hormone (GH)
thyroid-stimulating hormone (TSH)
follicle-stimulating hormone (FSH)
luteinizing hormone (LH)
prolactin (PRL)
adrenocorticotropic hormone (ACTH)
melanocyte-stimulating hormone (MSH)
Tropic hormones (tropins) are those hormones that influence other endocrine glands to secrete their hormone (s). Name them.
FSH
LH
TSH
ACTH
a. GROWTH HORMONE
Growth hormone (somatotropin or GH) stimulates protein synthesis, increased lipolysis, and the decreased use of glucose for ATP production, promoting hyperglycemia (the diabetogenic effect.
GH causes cells to increase their rate of amino acid uptake from the blood, especially during childhood and adolescence, thus promoting increased protein anabolism.
Control of GH secretion is via GH-Inhibiting Factor and GH-Releasing Factor from the hypothalamus and is related to blood glucose concentration.
Hypoglycemia inhibits GH-IF secretion, allowing GH-RF secretion and GH blood levels to rise.
Hyperglycemia inhibits GH-RF secretion, allowing GH blood levels to fall. this promotes normoglycemia.
GROWTH HORMONE
increased blood glucose decreased blood glucose
(hyperglycemia) (hypoglycemia)
(stimulates) (stimulates)
increased hypothalamic secretion increased hypothalamic secretion
of GH-IF of GH-RF
(inhibits) (stimulates)
anterior pituitary gland increased anterior pituitary gland
secretion of GH secretion of GH
(has the following effects)
decreased blood glucose 1. increased protein anabolism
2. increased lipolysis
3. increased glycogenolysis
(lead to)
increased blood glucose
normoglycemia
(Normoglycemia feeds back to turn off both the hypothalamus and anterior pituitary gland so that both GH-IF and GH-RF secretions are inhibited)
b. THYROID-STIMULATING HORMONE
HYPOTHALAMIC-PITUITARY-THYROID AXIS
decreased basal metabolic rate
(stimulates)
increased hypothalamic secretion of TSH-RF
(stimulates)
increased anterior pituitary gland secretion of TSH
(stimulates)
increased thyroid gland secretion of T3 and T4 (thyroxine)
(has the following effects))
1. increasing carbohydrate catabolism
2. increasing fat catabolism
3. increasing protein anabolism
(lead to)
increased basal metabolic rate
(This feeds back to turn off both the hypothalamus and anterior pituitary gland so that TSH-RF and TSH blood levels decline)
c. FOLLICLE-STIMULATING HORMONE
HYPOTHALAMIC-PITUITARY-GONADAL AXIS
(male – follicle stimulating hormone)
decreased blood levels of inhibin
(stimulates)
increased hypothalamic secretion of gonadotropin-RF
(stimulates)
increased anterior pituitary gland secretion of FSH
(stimulates)
1. increased spermatogenesis
2. increased activity of Sertoli cells
(leading to)
increased secretion of inhibin by Sertoli cells
(Inhibin feeds back to turn off both the hypothalamus and anterior pituitary gland so that Gn-RF and FSH blood levels decline)
HYPOTHALAMIC-PITUITARY-GONADAL AXIS
(female – follicle stimulating hormone)
decreased blood levels of estrogen
(stimulates)
increased hypothalamic secretion of gonadotropin-RF
(stimulates)
increased anterior pituitary gland secretion of FSH
(stimulates)
development of ovarian follicles
(has the following effects))
1. increasing blood levels of estrogen
2. maturation of an egg for ovulation
(leads to)
increased blood estrogen
(This feeds back to turn off both the hypothalamus and anterior pituitary gland so that Gn-RF and FSH blood levels decline)
d. LUTEINIZING HORMONE
HYPOTHALAMIC-PITUITARY-GONADAL AXIS
(male – luteinizing hormone)
decreased blood levels of testosterone
(stimulates)
increased hypothalamic secretion of gonadotropin-RF
(stimulates)
increased anterior pituitary gland secretion of LH
(stimulates)
increased secretion of testosterone
(has the following effects))
support of all male secondary sex characteristics
(Testosterone feeds back to turn off both the hypothalamus and anterior pituitary gland so that Gn-RF and FSH blood levels decline.)
HYPOTHALAMIC-PITUITARY-GONADAL AXIS
(female – luteinizing hormone)
increased blood levels of estrogen
(stimulates)
increased hypothalamic secretion of gonadotropin-RF
(stimulates)
increased anterior pituitary gland secretion of LHH
(stimulates)
1. directly stimulates ovulation,
2. which leads to formation of the corpus luteum
(has the following effects))
ovulation
(leads to)
formation of the corpus luteum
(After ovulation, blood estrogen falls below the level necessary ot stimulate the anterior pituitary gland. Therefore, this is not really inhibition of LH secretion. The anterior pituitary gland cannot secrete LH without sufficient blood estrogen.)
e. PROLACTIN
PROLACTIN
(female only)
increased estrogen during neuroendocrine reflex initiated by
last half of menstrual cycle suckling of postpartum nipple
(stimulates) (stimulates)
increased hypothalamic secretion increased hypothalamic secretion
of PRL-IF of PRL-RF
(inhibits) (stimulates)
anterior pituitary gland increased anterior pituitary gland
secretion of PRL secretion of PRL
has the following effects)
decreased blood PRL increased milk synthesis by mammary
gland cells (not secretion)
f. MELANOCYTE-STIMULATING HORMONE
MELANOCYTE STIMULATING HORMONE
increased hypothalamic increased hypothalamic secretion ofsecretion of MSH-IF MSH-RF
(inhibits) (stimulates)
anterior pituitary gland increased anterior pituitary gland
secretion of MSH secretion of MSH
(stimulates)
increased skin pigmentation by
stimulation of melanocytes
gland cells (not secretion)
(This hormone is poorly understood.)
g. ADRENOCORTICOTROPIC HORMONE
HYPOTHALAMIC-PITUITARY-ADRENAL AXIS
increased stress or decreased blood levels of glucocorticoids
(stimulates)
increased hypothalamic secretion of corticotropin-RF
(stimulates)
increased anterior pituitary gland secretion of ACTH
(stimulates)
increased adrenal cortex gland secretion of glucocorticoids (cortisol)
(has the following effects))
1. promote normal metabolism and ensure glucose availability by:
increasing protein catabolism
increasing gluconeogenesis
increased lipolysis
2. provide resistance to stress by:
increased mental alertness
increased energy
increased blood pressure
3. increased anti-inflammatory activity by:
stabilizing cell membranes
depressing phagocytosis
decreased capillary permeability (decreased swelling)
(lead to)
decreased stress
(This feeds back to turn off both the hypothalamus and anterior pituitary gland so that C-RF and ACTH blood levels decline)