Control of Secretion Rate

Most hormones controlled by negative feedback

systems
Most hormones are not secreted at constant rate,
but their secretion is regulated by three different
methods
1. The action of a substance other than a hormone on an
endocrine gland.
2. Neural control of endocrine gland.
3. Control of secretory activity of one endocrine gland
by hormone or neurohormone secreted by another
endocrine gland
1. Humoral stimulus: Action of Substance
Other Than Hormone
An increased blood glucose
concentration stimulates
increased insulin secretion from
the pancreas
Insulin increases glucose uptake
by tissues, which decreases
blood glucose levels.
Autonomic nervous system also
influences insulin secretion
Hypocalcemia stimulates PTH
secretion from parathyroids
Hypersecretion stimulates
calcitonin from parafollicular
cells
2. Nervous System Regulation
Stimuli such as stress or
exercise activate the
sympathetic division of the
autonomic nervous system
Sympathetic neurons stimulate
the release of epinephrine and
smaller amounts of
norepinephrine from the adrenal
medulla. Epinephrine and
norepinephrine prepare the
body to respond to stressful
conditions.
Once the stressful stimuli are
removed, less epinephrine is
released as a result of decreased
stimulation from the autonomic
nervous system.
3. Hormonal Regulation
Secretion of tropic
homones from hypotha-
lamus stimulates secre-
tion of anterior pituitary
homrones.
Example shows TRH
(thyrotropic releasing
hormone) from hypotha-
lamus stimulating secre-
tion of TSH from anterior
pituitary.
Note: TSH itself is a
tropic hormone in that it
stimulates T
3
/T
4
secretion.
Positive and Negative Feedback
POSITIVE
During the menstrual cycle, before
ovulation, small amounts of
estrogen are secreted from the
ovary.
Estrogen stimulates the release of
gonadotropin-releasing hormone
(GnRH) from the hypothalamus
and luteinizing hormone (LH)
from the anterior pituitary
GnRH also stimulates the release
of LH from the anterior pituitary
LH causes the release of additional
estrogen from the ovary. The
GnRH and LH levels in the blood
increase because of this positive-
feedback effect.

Positive and Negative Feedback
NEGATIVE
During the menstrual cycle,
after ovulation, the ovary
begins to secrete
progesterone in response to
LH.
Progesterone inhibits the
release of GnRH from the
hypothalamus and LH from
the anterior pituitary.
Decreased GnRH release
from the hypothalamus
reduces LH secretion from
the anterior pituitary. GnRH
and LH levels in the blood
decrease because of this
negative-feedback effect.
Changes in Hormone Secretion
Through Time
a) Chronic hormone regulation.
Maintenance of relatively
constant concentration of
hormone. Thyroid hormone.
b) Acute hormone regulation.
Epinephrine in response to
stress.
c) Cyclic hormone regulation.
Female reproductive
hormones.
Transport and
Distribution
Hormones dissolve in blood plasma and
are transported in free form or are
reversibly bound to plasma proteins
Free form can diffuse from plasma into
interstitial fluid and affect cells
As concentration of free hormone
molecules increase, more hormones
molecules diffuse from capillaries into
interstitial spaces to bind to target cells
Lipid soluble hormones diffuse through
capillary cells. Water soluble hormones
diffuse through pores in capillaries called
fenestrae.
A large decrease in plasma protein
concentration can result in loss of a
hormone from the blood because free
hormones are rapidly eliminated from
circulation through kidney or liver
Hormones are distributed quickly because
they circulate in the blood
Metabolism and Excretion
Half-life: The length of
time it takes for half a
dose of substance to be
eliminated from
circulatory system
Long half-life: regulate
activities that remain at
a constant rate through
time. Usually lipid
soluble and travel in
plasma attached to
proteins
Short half-life: water-
soluble hormones as
proteins, epinephrine,
norepinephrine. Have a
rapid onset and short
duration
Hormone (Ligand) Interaction with Target
Tissues
Portion of molecule where ligand
binds is called binding site.
If the molecule is a receptor (like in
a cell membrane) the binding site is
called a receptor site
Ligand/receptor site is specific; e.g.,
epinephrine cannot bind to the
receptor site for insulin.
The purpose of binding to target
tissue is to elicit a response by the
target cell.
Down-
Regulation
Normally, receptor molecules are
degraded and replaced on a
regular basis.
Down-regulation
Rate at which receptors are
synthesized decreases in some cells
after the cells are exposed to a
ligand.
Combination of ligands and
receptors can increase the rate at
which receptor molecules are
degraded. This combined form is
taken into the cell by phagocytosis
and then broken down.
Tissues that exhibit down-
regulation are adapted to short-
term increases in hormone
concentration.
Tissues that respond to hormones
maintained at constant levels
normally do not exhibit down-
regulation.

Up-Regulation
Some stimulus causes increase
in synthesis of receptors for a
hormone, thus increases
sensitivity to that hormone
For example, FSH stimulation
of the ovary causes an increase
of LH receptors. Ovarian cells
are now more sensitive to LH,
even if the concentration of LH
does not change. This causes
ovulation.


Membrane-Bound Receptors
Receptor: integral proteins with
receptor site at extracellular surface.
Interact with ligands that cannot pass
through the plasma membrane.
Ligands
Water-soluble or large-molecular-
weight hormones. Attachment of
ligand causes intracellular reaction.
Large proteins, glycoproteins,
polypeptides; smaller molecules
like epinephrine and
norepinephrine
Intracellular Receptors
Receptors: in the cytoplasm or
in the nucleus
Ligands
Lipid soluble and
relatively small molecules;
pass through the plasma
membrane.
React either with enzymes
in the cytoplasm or with
DNA to cause
transcription and
translation
Thyroid hormones,
testosterone, estrogen,
progesterone, aldosterone,
and cortisol
Membrane-Bound Receptors
Proteins or glycoproteins that have polypeptide chains
folded to cross cell membrane several times
Ligand binds reversibly to receptor site on receptor
protein
Three different results of ligand binding
1. Alteration of membrane permeability. Example:
acetylcholine
2. Activation of G proteins associated with the
membrane, causes production of intracellular mediator
such as cyclicAMP, leads to activation of intracellular
enzymes. Example: LH
3. Receptors linked to intracellular enzymes through
intracellular mediators. Mediators alter activity of
intracellular enzymes. Examples: nitric oxide,
cyclicGMP, Ca ions.
Intracellular Receptors
Proteins in cytoplasm or nucleus
Hormones bind with intracellular receptor and
receptor-hormone complex activate certain genes,
causes transcription of mRNA and translation.
These proteins (enzymes) produce the response of
the target cell to the hormone
Latent period of several hours because time is
required to produce mRNA and protein
Processes limited by breakdown of receptor-
hormone complex
Estrogen and testosterone produce different
proteins in cells that cause the differing secondary
sexual characteristics of females and males.

Anatomy and Physiology, Seventh Edition
Rod R. Seeley
Idaho State University
Trent D. Stephens
Idaho State University
Philip Tate
Phoenix College
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
*See PowerPoint Image Slides for all figures and tables pre-inserted into PowerPoint without notes.
Chapter 18
Lecture Outline
*
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
Hypothalamus
Where nervous and
endocrine systems interact
Hypothalamus regulates
secretions of anterior
pituitary
Posterior pituitary is an
extension of the
hypothalamus
Anterior pituitary produces
nine major hormones that
Regulate body functions
Regulate the secretions of
other endocrine glands
Pituitary Gland Structure
Posterior pituitary
(neurohypophysis): extension
of the nervous system via the
infundibulum
Secretes neurohormones
Anterior pituitary
(adenohypophysis)
Consists of three areas with
indistinct boundaries: pars
distalis, pars intermedia, pars
tuberalis

Hypothalamus, Anterior Pituitary, and Target Tissues
Releasing and Inhibiting Hormones
Tropins or tropic hormones: hormones that regulate the hormone secretions
of target endocrine tissues. All anterior pituitary hormones are tropins.
Releasing hormones secreted by the hypothalamus:
GHRH. Growth hormone-releasing hormone. Causes the anterior
pituitary to release growth hormone.
TRH. Thyroid-releasing hormone. Causes the anterior pituitary to
release thyroid-stimulating hormone (TSH).
CRH. Corticotropin-releasing hormone. Causes anterior pituitary to
produce adrenocorticotropic hormone (ACTH)
GnRH. Gonadotropin-releasing hormone. Causes anterior pituitary to
produce FSH (follicle stimulating hormone) and LH (luteinizing
hormone).
PRH. Prolactin-releasing hormone. Causes the anterior pituitary to
release prolactin.
Inhibiting hormones:
GHIH. Growth hormone-inhibiting hormone, somatostatin. Causes
the anterior pituitary to decrease release of growth hormone.
PIH. Prolactin-inhibiting hormone. Causes the anterior pituitary to
decrease release of prolactin.
Hypothalamus, Posterior Pituitary and Target
Tissues

Hypothalamic neurons
syntheisze ADH and
oxytocin.
Latter hormones travel
to post. pituitary via
axons of hypothalamic
neurons.
ADH and oxytocin
enter circulation in post.
pituitary.
Hormones of Posterior Pituitary: ADH
Antidiuretic hormone (ADH). Also called vasopressin.
A. Osmoreceptors (specialized neurons of
hypothalamus monitor changes in intercellular
osmolality (relative concentrations of electrolytes and
water). If the concentration of electrolytes increases
or if the concentration of water decreases, then ADH
secretion is stimulated.
B. Baroreceptors (specialized neurons found in walls of
atria of heart, large veins, carotid arteries, aortic arch)
sense changes in blood pressure (BP). If BP
decreases, then ADH secretion is stimulated.
Control of ADH Secretion
Control of Oxytocin Secretion
Anterior Pituitary Hormones
Growth hormone (GH) or somatotropin
Thyroid-stimulating hormone (TSH)
Adrenocorticotropic hormone (ACTH)
Melanocyte-stimulating hormone
(MSH)
Beta endorphins
Lipotropins
Luteinizing hormone (LH)
Follicle-stimulating hormone (FSH)
Prolactin

Growth Hormone (GH or somatotropin)
Stimulates uptake of amino acids; protein
synthesis; growth in most tissues.
Stimulates breakdown of fats to be used as
an energy source but stimulates synthesis of
glycogen: glucose sparing
Promotes bone and cartilage growth
Regulates blood levels of nutrients after a
meal and during periods of fasting
Stimulates glucose synthesis by liver
Figure 16.6
Metabolic Action of Growth
Hormone
Growth Hormone Stimulation: functions in
regulating growth, tissue maintenance, metabolism
GHRH from hypothalamus causes release of
Growth hormone from anterior pituitary effects
Target tissues: most tissues of the body
Direct effect: GH binds to receptors on cells and causes
changes within the cells. Increased lipolysis and decreased
use of glucose for energy
Indirect effect: causes liver and skeletal muscle to produce
somatomedins; e.g., insulinlike growth factors (IGFs)
Insulinlike growth factors: bind to receptors on
membranes of target cells. Stimulate growth in
cartilage, bone; increased synthesis of proteins in
skeletal muscle.
Regulation of GH Secretion
1. Stress and decreased glucose
levels increase release of GHRH
and decrease release of GHIH.
2. GHRH and GHIN travel via
thehypothalamohypophyseal
portal system to ant. pituitary
3. Increased GHRH and reduced
GHIH act on AP and result in
increased GH secretion.
4. GH acts on target tissues.
5. Increasing GH levels have neg
feedback effect on hypothala.
Growth Hormone: Inhibition
Hypothalamus produces growth hormone inhibiting
hormone (GHIH = somatostatin)
Inhibits production of GH by anterior pituitary.
GHRH secretion in response to low blood glucose, stress,
increase in certain a.a.
GHIH secretions in response to high blood glucose.
Peak GH levels during deep sleep; levels lower at other
times of day.
Hyposecretion of GH may result in dwarfism
Hypersecretion may result in giantism or acromegaly de-
pending on ossification of epiphyseal plates
TSH and Thyroid Hormones
TRH from hypothalamus causes the release
of TSH from anterior pituitary which
causes secretion and storage of hormones
T
3
and T
4
from and within the thyroid gland
TSH increases activity of phospholipase
that opens Ca
2+
channels, increasing Ca
2+

concentration in cells of the thyroid gland
T3 and T4 inhibit TRH and TSH secretion
Adrenocorticotrophic Hormone (ACTH)
CRH from hypothalamus causes release of
ACTH from anterior pituitary which
Causes cortisol secretion from the adrenal
cortex (a glucocorticoid from the zona
fasciculata)
Causes aldosterone secretion from the
adrenal cortex (a mineralocorticoid from
the zona glomerulosa)
Binds directly to melanocytes of the skin;
causes increase in production of melanin.


Melanocyte Stimulating Hormone,
Endorphins, and Lipotropins
ACTH, MSH, endorphins and lipotropins all derived
from the same large precursor molecule when stimulated
by CRH
MSH causes melanocytes to produce more melanin
Endorphins act as an analgesic; produced during times of
stress.
Lipotropins cause adipose cells to catabolize fat


LH, FSH, Prolactin
Gonadotrophs: glycoprotein hormones that promote
growth and function of the gonads
LH and FSH
Both hormones regulate production of gametes and
reproductive hormones
Testosterone in males
Estrogen and progesterone in females
GnRH from hypothalamus stimulates LH and FSH
secretion
Prolactin: role in milk production
Regulation of secretion: prolactin-releasing hormone (PRH)
and prolactin-inhibiting hormones (PIH)
Thyroid
Gland
One of largest endocrine glands; Highly
vascular. Iodine enters follicular cells by active
transport. Only gland that stores hormone.
Histology
Composed of follicles: follicular cells
surrounding thyroglobulin/thyroid
hormones
Parafollicular cells: between follicles
Physiology
Follicular cells secrete thyroglobulin into
lumen of follicle. Iodine and a.a. tyrosine
necessary for production of T3 and T4.
Hormones stored here attached to the
thyroglobulin then absorbed into follicular
cells; hormones disattached from
thyroglobulin and released into circulation.
Parafollicular cells. Secrete calcitonin
which reduces [Ca2+] in body fluids when
Ca levels are elevated.
Biosynthesis of Thyroid
Hormones
Thyroid Hormones
Produced by follicular cells
Triiodothyronine or T
3
-less produced

Tetraiodothyronine or T
4
or thyroxine-more
99.6% of thyroxine in the blood is bound to thyroxine-
binding globulin (TBG) from the liver. Rest is free.
TBG has a higher affinity for T
4
than for T
3
; amt of free
unbound T
3
in plasma is 10xs greater than free T
4.
Only free thyroxine and T
3
can enter cells; bound-
thyroxine serves as a reservoir of this hormone
33-40% of T
4
converted to T
3
in cells: T
3
more potent
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 presence
of thyroid hormones.
Effects of T
3
and T
4

1. Maintain normal rate of metabolism.
2. Increase the rate at which glucose, fat, and protein are meta-
bolized.
3. Increase the activity of Na
+
-K
+
pump which increases body
temperature.
4. Can alter the number and activity of mitochondria resulting in
greater ATP synthesis and heat production.
5. Normal growth and maturation of bone, hair, teeth, c.t., and
nervous tissue require thyroid hormone.
6. Both T
3
and T
4
play a permissive role for GH and GH does not
have its normal effect on tissues if T
3
and T
4
are lacking.
7. See Table 18.4 for effects of hypo- and hypersecretion
Regulation of T
3
and T
4
Secretion

Regulation of Calcitonin Secretion
Produced by parafollicular cells
Secretion triggered by high Ca
2+
concentration in blood; acts to decrease
Ca
2+
concentration
Primary target tissue: bone. Decreases
osteoclast activity, lengthens life span
of osteoblasts.
Parathyroid Glands
Embedded in thyroid
Two glands on each side
Secrete PTH: target tissues are
bone, kidneys and intestines.
Increases blood calcium and
phosphate levels
Stimulates osteoclasts
Promotes calcium reabsorption by
kidneys and PO4 excretion
Increases synthesis of vitamin D
which, in turn, increases absorption
of Ca and PO4 by intestines. Net
loss of PO4 under influence of
PTH.
Regulation depends on calcium
levels.
Figure 16.11
Effects of Parathyroid Hormone
Adrenal Glands
Near superior poles of
kidneys; retroperitoneal
Inner medulla; outer
cortex
Medulla: formed from
neural crest; sympathetic.
Secretes epinephrine and
norepinephrine
Cortex: three zones from
superficial to deep
Zona glomerulosa
Zona fasciculata
Zona reticularis
Adrenal Medulla
Secretory products are neurohormones: epinephrine and norepinephrine
Combine with adrenergic membrane-bound receptors
All function through G protein mechanisms
Secretion of hormones prepares body for physical activity
Effects are short-lived; hormones rapidly metabolized
Epinephrine
Increases blood levels of glucose
Increases fat breakdown in adipose tissue
Causes dilation of blood vessels in skeletal muscles and cardiac muscles.
Epinephrine and norepinephrine increase heart rate and force of contraction;
cause blood vessels to constrict in skin, kidneys, gastrointestinal tract, and
other viscera
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
Weak androgens secreted then converted to testosterone
by peripheral tissues. Stimulate pubic and axillary hair
growth and sexual drive in females

Regulation of Cortisol Secretion
Help the body resist stress by:
Keeping blood sugar levels relatively constant
Maintaining blood volume and preventing water shift
into tissue
Cortisol provokes:
Gluconeogenesis (formation of glucose from
noncarbohydrates)
Rises in blood glucose, fatty acids, and amino acids
Glucocorticoids (Cortisol)
Figure 16.15
Stress and the Adrenal Gland
Pancreas
Located along small intestine and
stomach; retroperitoneal
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
A 29-amino-acid polypeptide hormone that is a
potent hyperglycemic agent
Its major target is the liver, where it promotes:
Glycogenolysis the breakdown of glycogen to
glucose
Gluconeogenesis synthesis of glucose from lactic acid
and noncarbohydrates
Release of glucose to the blood from liver cells
Glucagon
Target tissue is the liver, adipose tissue, muscle,
and satiety center of hypothalamus
A 51-amino-acid protein consisting of two amino
acid chains linked by disulfide bonds
Synthesized as part of proinsulin and then excised
by enzymes, releasing functional insulin
Insulin:
Lowers blood glucose levels
Enhances transport of glucose into body cells
Counters metabolic activity that would enhance blood
glucose levels
Insulin
Regulation of Blood Glucose Levels
The
hyperglycemic
effects of
glucagon and
the
hypoglycemic
effects of
insulin
Figure 16.17
Results from hyposecretion or hypoactivity of
insulin
The three cardinal signs of DM are:
Polyuria huge urine output
Polydipsia excessive thirst
Polyphagia excessive hunger and food consumption
Hyperinsulinism excessive insulin secretion,
resulting in hypoglycemia
Diabetes Mellitus (DM)
Figure 16.18
Diabetes Mellitus (DM)
Regulation of Insulin Secretion
Regulation of Blood Nutrient Levels
Regulation of Blood Nutrient Levels
During Exercise
Hormones of the Reproductive System
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 and arginine
vasotocin
Thymus Gland, GI Tract, Kidneys
Thymosin. Development of the immune
system.
GI tract: several hormones regulate
digestion and enzyme secretion. Studied
with digestive system.
Kidneys secrete erythropoietin, which
signals the production of red blood cells
Adipose tissue releases leptin, which is
involved in the sensation of satiety, and
stimulates increased energy expenditure

Hormone-like Substances
Autocrines: chemical signals released by a cell and the
substance affects that same cell.
Chemical mediators of inflammation which are
modified fatty acids: eicosanoids such as
prostaglandins, thromboxanes, prostacyclins, and
leukotrienes
Paracrines: chemical signals released into intercellular
fluid and affecting nearby cells.
Endorphins and enkephalins modulate sensation of pain
Several growth factors
Effects of Aging on
Endocrine System
Gradual decrease in secretory activity of some glands
GH as people age except in people who exercise regularly
Melatonin
Thyroid hormones
Kidneys secrete less renin
Familial tendency to develop type II diabetes