Download 2,3,4-Anterior Pituitary 12017-02-05 00:361.9 MB

The Endocrine Physiology
The Pituitary Gland
Dr. Khalid Alregaiey
Learning Objectives
• List the functional parts (lobes) of the pituitary gland.
• Describe the relationships of the hypothalamus to the anterior and
posterior pituitary glands.
• Describe the hypothalamo-hypophyseal portal system.
• Explain the physiological significance of the hypothalamohypophyseal portal system in regulating anterior pituitary
functions.
• List the hypothalamic hormones and their target cells in the
anterior pituitary.
• List the anterior pituitary hormones and their target tissues.
• Summarize the functions of the anterior pituitary hormones.
• Outline the different feedback loops regulating secretion of
anterior pituitary hormones.
• Summarize the direct and indirect physiological actions of growth
hormone.
• Outline neuroendocrine control of growth hormone secretion
• List stimuli that increase and decrease growth hormone secretion
• Describe the role of prolactin in milk secretion.
• Discuss regulation of prolactin secretion.
Hypothalamus
• hypothalamus is located at the base of the brain. It
is part of the limbic system, which controls the
autonomic nervous system and the endocrine
systems.
• One of the most important functions of the
hypothalamus is to link the nervous system to
the endocrine system via the pituitary gland
(hypophysis).
• Secretes releasing hormones to cause the pituitary to
release hormones
• Secretes inhibiting hormones to turn off secretion of
pituitary hormones
Three Methods of Hypothalamic Control over
the Endocrine System
Hormones of the Hypothalamus
HORMONES
TARGET
stimulates release of TSH and prolactin
(PL)
stimulates the release of gonadotrophins
(FSH, LH)
TRH (thyrotropin releasing hormone)
GnRH (gonadotropin releasing hormone)
CRH (corticotropin releasing hormone)
stimulates release of ACTH
ANTERIOR
PITUITARY
GHIH (growth hormone release inhibiting hormone GLAND
GHRH (growth hormone releasing hormone)
or somatostatin (SMS))
PRH (prolactin releasing hormone), also called
prolactin releasing factor (PRF) ?
PIH (prolactin inhibiting hormone), also called
prolactin inhibiting factor. This hormone or factor is
dopamine
Oxytocin
ADH (Vasopresin)
FUNCTION
stimulates release of GH
inhibits release of GH
stimulates release of PL
inhibits release of PL
POSTERIOR
PITUITARY
GLAND
uterine contractions; milk let-down
water balance
Pituitary (Hypophysis)
• pituitary gland, also called the hypophysis, is
a small gland—about 1 cm in diameter and 0.5 to 1
gram in weight— that lies in the sella turcica, a
bony cavity at the base of the brain, and is
connected to the hypothalamus by the pituitary
(or hypophysial) stalk.
Pituitary (Hypophysis)
• Neurohypophysis – posterior lobe (neural
tissue) and the infundibulum
• Receives, stores, and releases hormones from
the hypothalamus
• Adenohypophysis – anterior lobe, made up of
glandular tissue
• Synthesizes and secretes a number of
hormones
The Anatomy and Orientation of the Pituitary
Gland
Pituitary-Hypothalamic Relationships:
Anterior Lobe
• The anterior lobe of the pituitary is an
outpocketing of the oral mucosa
• There is no direct neural contact with the
hypothalamus
• There is a vascular connection, the hypophyseal
portal system,
Hypophyseal portal system
• At the median eminence, terminals of
hypothalamic neurons release regulatory factors
into the tissue fluids then taken by fenestrated
capillaries down to the anterior lobe.
• Releasing hormones
• Inhibiting hormones
• All blood entering the portal system will reach the
intended target cells before returning to the
general circulation
The Hypophyseal Portal System
Pituitary (Hypophysis)
Pituitary-Hypothalamic Relationships:
Posterior Lobe
• Has a neural connection with the hypothalamus
(hypothalamic-hypophyseal tract)
• Nuclei of the hypothalamus (supraoptic and
paraventricular) synthesize oxytocin and
antidiuretic hormone (ADH)
• These hormones are transported to the posterior
pituitary
Cells Types of the Anterior Pituitary
• Five cell types in the anterior pituitary:
1. Somatotropes—human growth hormone (hGH)
2. Corticotropes—adrenocorticotropin (ACTH)
3. Thyrotropes—thyroid-stimulating hormone
(TSH)
4. Gonadotropes—gonadotropic hormones, which
include both luteinizing hormone (LH) and
folliclestimulating hormone (FSH)
5. Lactotropes—prolactin (PRL)
Adenophypophyseal Hormones
• The six hormones of the adenohypophysis:
• Are abbreviated as GH, TSH, ACTH, FSH, LH,
and PRL
• Regulate the activity of other endocrine glands
• In addition, pro-opiomelanocortin (POMC):
• Has been isolated from the pituitary
• Is enzymatically split into ACTH, opiates, and
MSH
Adenohypophyseal Cells & Hormones
Cell
Corticotropes
Hormone
Chemistry
Adrenocorticotropic
hormone (corticotropin; ACTH)
Physiologic Actions
Single chain of 39
amino acids
Stimulates production of glucocorticoids
and androgens by the adrenal cortex;
maintains size of zona fasciculata and
zona reticularis of cortex
Stimulates production of thyroid hormones,T4
Thyrotropes
Gonadotropes
Gonadotropes
Thyroid-stimulating
hormone (thyrotropin; TSH)
Follicle-stimulating
hormone (FSH)
Lutenizing hormone
(LH)
Glycoprotein having two
and T3, by thyroid follicular cells;maintains size
subunits,  (89 amino acids) of follicular cells
and ß (112 amino acids)
Glycoprotein having two subunits,  (89aa) and ß (115aa)
Stimulates development of ovarian follicles;
regulates spermatogenesis in the testis
Causes ovulation and formation of corpus
luteum in the ovary; stimulates production of
Glycoprotein having two sub- estrogen and progesterone by the ovary;
units,  (89aa) and ß (115aa) stimulates testosterone production by the testis
Single chain of 198
amino acids
Mammotropes,
Lactotropes
Prolactin (PRL)
Somatotropes
Growth hormone
Single chain of 191
(somatotropin; GH) amino acids
Essential for milk production by lactating
mammary gland
Stimulates postnatal body growth; stimulates
secretion of IGF-1; stimulates triglyceride
lipolysis; inhibits actions of insulin on carbohydrate and lipid metabolism
Growth Hormone (GH)
• growth hormone (GH) is a protein
hormone secreted by somatotropes
(somatotrophs), which make up around
40% of the anterior pituitary gland.
• GH has many target tissues including
bone, skeletal muscle, liver and adipose
tissue.
Growth Hormone (GH)
• Antagonistic hypothalamic hormones regulate GH
• Growth hormone–releasing hormone (GHRH)
stimulates GH release
• Growth hormone–inhibiting hormone (GHIH)
inhibits GH release
Growth hormone promotes growth of many body cells
• Promote increased size of the cells
• Increased mitosis
• Specific differentiation of certain types of cells
such as bone growth cells and early muscle cells
Indirect physiological role of GH (GH and growth)
Mechanism of action of IGF-1:
Increases amino acids uptake
by chondrocyres.
Stimulates protein synthesis
by chondrocyres.
Stimulates mitosis of
chondrocytes. This effect
causes an increase in number
of chondrocytes (i.e.,
hyperplasia).
Stimulates expansion in size
of the chondrocytes (i.e.,
hypertrophy).
Thus, IGF-1 leads to elongation
of the bones.
Growth hormone has several metabolic effects
1- Increased rate of proteins synthesis
in most cells of the body
2- Increased mobilization of fatty acids
from adipose tissue, increased free
fatty acid in the blood, and increased
use of fatty acids for energy.
3- Decreased rate of glucose utilization
through the body
Increased rate of proteins synthesis in most cells
of the body (anabolic effect)
GH promotes protein deposition in tissues :
• enhancement of amino acid transport through the
cell membrane
• enhancement of RNA translation to cause protein
synthesis by the ribosomes
• Increased nuclear transcription of DNA to form
RNA
• Decreased catabolism of protein and amino acids
Increased Mobilization of Fatty Acids
• release of fatty acids from adipose tissue
• increasing the FFA in the body fluids
• conversion of FFA to acetyl coemzyme A
• fat is used for energy in preference to the use of
carbohydrates and proteins.
• High GH levels might cause excessive fat
mobilization leading to acetoacetic acid formation
by the liver>>> causing ketosis>>>fatty liver.
Decreased rate of glucose utilization through the
body (decrease carbohydrate utilization)
• Decreased glucose uptake in tissues such as
skeletal muscle and fat
• Increased glucose production by the liver
• increased insulin secretion (cause insulin
resistance).
• Excess secretion of growth hormone =metabolic
disturbances very similar to patients with type II
diabetes. (diabetogenic effect)
Necessity of insulin and carbohydrate for the growth
promoting action of growth hormone
• Animal +lacks of pancreas>>>>no growth
hormone effect
• Animal+ diet without carbohydrate >>>> no
growth hormone effect
• Carbohydrate and insulin>>production of energy
• Insulin : transport of amino acids into cells and
glucose transport stimulation
Growth hormone stimulates cartilage and bone
Growth
• Increased deposition of protein by the
chondrocytic and osteogenic cells that cause bone
growth
• Increased rate of reproduction of these cells
• Converting chondrocytes into osteogenic cells,
thus causing deposition of new bone
• Strongly stimulates osteoblast activity.
Somatomedins (insulin Like Growth factor-1)
• Chondrocytes cultured outside the body+ growth
hormone= proliferation or enlargement fails.
• Growth hormone +inside body= proliferation and
growth of cells
Factors Affecting GH Secretion
Stimulation
Glucose decrease
Free fatty acid decrease
Amino acid increase (arginine)
Fasting
Prolonged caloric deprivation
Stress
Exercise
Puberty
Androgens and estrogens
Sleep
Inhibition
Somatostatin
Glucose increase
Free fatty acid increase
IGF-1
Growth hormone
Senescence
Metabolic vs. Growth actions of Growth Hormone
• Metabolic actions of growth hormone are directly
induced by the GH through its receptor.
• Growth actions are mediated by insulin-like
growth factor 1 (IGF-1)
Metabolic Action of Growth Hormone
Hyposecretion of GH; Dwarfism
Dwarfism means failure in growth (i.e., growth retardation).
It is caused usually by defective HGH axis (hypothalamic-anterior
pituitary-liver-target organs axis).
Thus, dwarfism can be caused by decreased secretion of GHRH, HGH or
IGF-I. There may be a defect in the GH receptors.
Other causes of dwarfism include deficiency of thyroid hormones in
childhood.
Hyposecretion of GH; Dwarfism
Normal and
abnormal
growth
Hypersecretion of HGH
Gigantism and acromegaly
Excessive production of GH from a GHsecreting pituitary tumour (somatotropes
tumours)can cause gigantism if excessive
GH production occurs when the body is
growing (in childhood and at puberty), i.e.,
before the epiphyseal growth plates fuse.
Tumors in adulthood (after epiphyseal
closure) cause acromegaly.
Pituitary gigantism
Acromegaly
Clinical features:
Excessive soft tissue growth
1- prominent supraorbital ridge.
2- Prognathism.
3- Ride-spaced teeth (widening of
incisor spaces).
4- Increase shoe size.
5- Thick spade-like hands
6- Deepening voice.
7- Macroglossia.
Befor
e
After
Prolactin (PL)
Prolactin (PL) is secreted from mammotrophs (lactotrophs) in
the anterior pituitary.
Control of PL secretion:
•
Hypothalamic control of PL secretion is performed primarily
by dopamine. Thus, pituitary stalk lesions cause
hyperprolacinaemia.
•
The hypothalamic PRH (prolactin releasing hormone), also
called prolactin releasing factor (PRF) stimulates release of
PL ? The hypothalamic TRH stimulates release of PL.
•
PL secretion is increased during pregnancy and suckling.
•
PL causes increased PIH (dopamine) secretion, i.e., it inhibits
its own secretion.
Prolactin (PL)
Main target organ:
Mammary gland (breast).
Effects in females:
PL plays an important role in the normal development (growth) of the
mammary gland and milk synthesis (production) during lactation.
PL inhibits GnRH, FSH and LH secretion.
PL antagonizes the actions of FSH and LH. Thus, ovulation is often
inhibited by breast feeding.
Effects in males:
In males, PL is involved in testicular function.
Effects of PL and control of its secretion
Thyroid Stimulating Hormone (Thyrotropin)
• Tropic hormone that stimulates the normal
development and secretory activity of the thyroid
gland
• Triggered by hypothalamic peptide thyrotropinreleasing hormone (TRH)
• Rising blood levels of thyroid hormones act on the
pituitary and hypothalamus to block the release of
TSH
The hypothalamic-pituitary-thyroid axis
Thyrotropin releasing
hormone (TRH) is produced
in the hypothalamus. It
reaches the thyrotrophs in
the anterior pituitary by the
hypothalamic-hypophysialportal system.
TRH stimulates the
synthesis and release of TSH
by the thyrotrophs from the
anterior pituitary.
In both the hypothalamus
and the pituitary, it is
primarily T3 that inhibits
TRH and TSH secretion,
respectively.
The hypothalamic-pituitary-adrenal axis
Corticotropin-releasing hormone or
factor (CRH or CRF) is produced ) is
produced in the hypothalamus.
It reaches the corticotrophs in the
anterior pituitary by the hypothalamichypophysial-portal system.
CRH stimulates the synthesis of
adrenocorticotrophic hormone (ACTH).
ACTH stimulates the synthesis of
adrenal steroid hormones.
Glucocorticoids (cortisol) released into
the systemic circulation exert negative
feedback inhibition of CRF and ACTH
release from the hypothalamus and
pituitary, respectively.
Gonadotropins
• Gonadotropins – follicle-stimulating hormone
(FSH) and luteinizing hormone (LH)
• Regulate the function of the ovaries and testes
• FSH stimulates gamete (egg or sperm)
production
• Absent from the blood in prepubertal boys and
girls
• Triggered by the hypothalamic gonadotropinreleasing hormone (GnRH) during and after
puberty
Functions of Gonadotropins
• In females
• LH works with FSH to cause maturation of the
ovarian follicle
• LH works alone to trigger ovulation (expulsion
of the egg from the follicle)
• LH promotes synthesis and release of estrogens
and progesterone
Functions of Gonadotropins
• In males
• LH stimulates interstitial cells of the testes
(Leydig cells) to produce testosterone
• FSH targets Sertoli cells in the seminiferous
tubules of the testes and promotes
spermatogenesis