Transcript growth hormone

Chapter 4. The Hypothalamus
and Pituitary Part II
The Anterior Pituitary
Reference - Textbook
Reference – Course Website
3
The Anterior Pituitary
• Introduction
• Growth Hormone
• Prolactin
INTRODUCTION
Important peptide hormones that secreted by
the anterior pituitary and the targets
TSH, Thyroid stimulating
hormone
ACTH, Adrenocorticotropin
hormone
FSH, Follicle-stimulating
hormone
LH, Luteinizing hormone
MSH, Melanophorestimulating hormone
GH, Growth Hormone
PRL, Prolactin
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Anatomical Relationship Between the
Hypothalamus and Anterior Pituitary
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Hormones Secreted by the Hypothalamus
and Their Effects on Anterior Pituitary
8
Growth Hormone and Prolactin
9
Receptor and Transmembrane Signaling
• Member of cytokine receptors
– Signals through JAK-STAT pathway
• Located throughout the body
– GH hormones: Most significant in liver, muscle and adipose
– Prolactin Receptors: breast, liver, ovary and prostate
GROWTH HORMONE
Change of Mr. Robert in 37 Years
28 yrs
49 yrs
55 yrs
65 yrs
Greenspan & Strewler, Basic & Clinical Endocrinology, 5th Ed., 1997
From Reichlin S. Acromegaly. Med Grand Rounds 1982;1:9
The Problem of Mr. Robert
• Case history (In 5 years)
–
–
–
–
Develop swelling in hands and feet
Pins and needles in hands
Increased sweating, particularly at night
Pain in the left hip on walking
The Problem of Mr. Robert
• Signs and Syndromes
– Large
• Feet and hands
• Jaw –
– lower teeth protruded in front of the upper teeth
– Teeth widely separated
• Tongue
• Chest – like a barrel
– Blood pressure 155/95 mmHg
– Blood glucose 12 mmol/L
Question
•
•
•
•
What cause the problem?
Diagnosis?
Mechanism?
Treatment?
Physiological Functions
• Growth
• Regulation of Metabolism
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Plasma Concentration of GH
• Decline with age
– 5 – 20 years old, 6 ng/ml
– 20 – 40 years old, 3 ng/ml
– 40 –70 years old, 1.6 ng/ml
• Circadian
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Growth Effect
• stimulates cell division
– muscle and epiphyseal cartilage （骨骺软骨）
of long bones.
•
muscular growth as well as linear growth
– Growth of heart, skin, connective tissue, liver, kidney,
pancreas, intestines, adrenals and parathyroids
– Hypersecretion leads to cause gigantism in children
and acromegaly in adult.
– Hyposection results in dwarfism during childhood.
Receptor
mechanism of the
growth hormone
effect
GH
somatomedins (SM)
（also called
insulin-like growth
factor, IGF) in the
liver
growth
of bone and other
peripheral tissues.
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Dwarfism
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Growth of Epiphyseal Cartilage
Following GH Treatment
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Dwarfism
Treatments for Dwarfism
• Daily injections of Human
Growth Hormone (HGH)
• rhGH, developed in 1985
• $10,000-40,000 a year
depending on severity
GIGANTISM
Tallest Man to ever Live: Robert
2.72 m, lived to age 22
Tallest Woman to ever Live: Zeng Jinlian:
2.45 m, lived to age 17
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Acromegaly
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Regulation of Metabolism
• Protein Metabolism
• Fat metabolism
• Glucose metabolism
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On Protein Metabolism
• increase rate of protein synthesis by
– enhance amino acid transport to the interior
of the cells
– increase RNA translation and nuclear
transcription of DNA to form mRNA
• reduces the breakdown of cell proteins
On Fat Metabolism
• Cause release of fatty acids from adipose
tissue
– increase the concentration of fatty acids.
– utilization of fat for providing energy in
preference to both carbohydrates and proteins.
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On Glucose Metabolism
• Decreases cellular uptake of glucose and
glucose utilization
– leads to increase of the blood glucose
concentration.
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Regulation of GH Secretion
• Role of hypothalamus and feedback
mechanism
• Other factors
Role of hypothalamus and feedback mechanism
-
Hypothalamus
GRH
-
- SS
+
Pituitary
-
GH
Liver
SM
Target tissues
+ increase the secretion; - inhibit the secretion
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Other factors that affect the GH
secretion
• Starvation, especially with severe protein deficiency
• Hypoglycemia or low concentration of fatty acids in the
blood
• Exercise
• Excitement
• Stress (trauma)
• Sex
• Sleep
• Other Hormones, such as thyroid hormone, estrogen,
testosterone, glucogen
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Change of Mr. Robert in 37 Years
28 yrs
49 yrs
55 yrs
65 yrs
Greenspan & Strewler, Basic & Clinical Endocrinology, 5th Ed., 1997
From Reichlin S. Acromegaly. Med Grand Rounds 1982;1:9
The Problem of Mr. Robert
• Case history (In 5 years)
– Develop swelling in hands and feet
– Pins and needles in hands
– Increased sweating, particularly at night
– Pain in the left hip on walking
The Problem of Mr. Robert
• Signs and Syndromes
– Large
• Feet and hands
• Jaw –
– lower teeth protruded in front of the upper teeth
– Teeth widely separated
• Tongue
• Chest – like a barrel
– Blood pressure 155/95 mmHg
– Blood glucose 12 mmol/L
Pathophysiology of Acromegaly
• Arthritis
– Overstimulation of cartilage and peri-articular bone
• High Blood Pressure
– The internal organ grow and the resulting cardiac
hypertrophy
• Sweating
– Growth of skin and sweat gland
• Carpal tunnel syndrome
– Growth of the soft tissue surrounding the medial nerve
resulting in compression under the carpal tunnel
Carpal tunnel syndrome (腕管综合征）
– Growth of the soft tissue surrounding the medial
nerve resulting in
• compression under the carpal tunnel
PROLACTIN
Physiological Function
•
•
•
•
On breast development and prolactation
On Sexual organs
On Stress
On immunological function
Breast Development
• In women
– breasts development at puberty
– stimulated by estrogen, progesterone, growth
hormone, cortisol, insulin, thyroid hormones and
prolactin.
• During pregnancy
– great growth of breast tissues
•
•
by stimulation of estrogen, progesterone and prolactin
estrogen and progesterone inhibit the secretion of milk.
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Lactation
• Immediately after the baby is born,
– sudden loss of estrogen and progesterone
secreted by the placenta allows
• lactogenic effect of PRL initiating milk secretion
• Widely used in dairy farming （乳品业）
Lactation (cont.)
• After birth of the baby
– the basal level of PRL returns to normal
– Lactation is maintained by surge in Prolactin secretion
• nursing baby causes a 10 to 20 fold secretion of PRL and lasts for 1 h
• Unconditioned and conditioned reflex
– Prolactin surge inhibit gonadotropin releasing hormone (GnRH)
• Inhibits ovulation
• Natural contraception
Effect on sexual organs
• In women
– combined with PRL receptors in granulosa cells in ovary
– stimulates production of LH receptors (permissive effect)
• LH promotes ovulation and then formation of corpus luteum.
(permissive effect)
• In male,
– Promotes growth of prostate glands and seminal vesicle
– Enhances the effect of LH on the interstitial cells to
produce testosterone.
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Regulation of Prolactin Secretion
• Hypothalamic hormones and feedback
mechanism
• Milk ejection reflex
Hypothalamic Hormones and
Feedback Mechanism
Hypothalamus: PIF
PRF
+
Anterior pituitary: Prolactin
+
• PIF
• Dopamine
• Tonic inhibitory
control
• PRF
• TRH（thyrotropin
releasing
hormone)
• Less physiological
importance
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Milk ejection reflex
Sucking, tactile stimulation
Afferent nerve (somatic nerve)
Centers including spinal cord and hypothalamus
PRF secretion
PRL secretion
Milk production increase
Oxytocin secretion
Myoepithelial cells contraction of
mammary glands
Milk flows
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PROLACTIN
SECRETION
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Hyperprolactinaemia
• Caused by Excess secretion of Prolactin
– Prolactinoma （泌乳素瘤）
– Tumor in the pituitary fossa
– Adverse effect of drug that reduce dopaminergic
transmission
• Antipsychotic Drugs – Risperidone （利培酮）
• Signs and Symptoms
– Galactorrhoe （溢乳症）in women
• Cessation of the menstrual cycle
• Inappropriate lactation
– Gynaecomastia （男性乳房发育症）in men
• Growth of breast tissue
Hypopituitarism
• Caused by
–
–
–
–
Trauma
Infarction
Hypophysectomy
Space-occupying tumours affect
• Growth hormone
• LH/FSH
• ACTH and TSH
• Panhypopituitarism (全垂体功能减退症）
–
–
–
–
Hypotension
Hypglycomia
Lethargy
Weekness