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` ENDOCRINE PHYSIOLOGY PART 2: PITUITARY GLAND –DR. BARBON
LEA THERESE R. PACIS 1
ENDOCRINE PHYSIOLOGY PART 2: PITUITARY GLAND
Dr. Felipe Barbon
I. ANTERIOR PITUITARY GLAND (ADENOHYPOPHYSIS)
Types of Adenohypophyseal Cells
Staining Characteristics
- Granular
Acidophils (40%) – Growth Hormone, Prolactin
Basophils (10%) – Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Thyroid
Stimulating Hormone (TSH), Adrenocorticotropic Hormone (ACTH)
- Agranular Chromophobes – Adrenocorticotropic Hormone (ACTH) Secretory Activity
- Somatotropes – Growth Hormones (GH)/Somatotropin (STH); about 50%
- Lactotropes (Mammosomatotropes) – Prolactin (PRL); 10-25%
- Thyrotropes – Thyroid Stimulating Hormone (TSH); <10%
- Gonadotropes – Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH); 10-15%
- Corticotropes (POMC Cells -- Pro-opiomelanocort in Cells) – Adrenocorticotropic Hormones
(ACTH) and β-Lipotropic Hormone (β-LPH); 15-20%
- Mammosomatotropes – Growth Hormone (GH), Prolactin (PRL)
A. GROWTH HORMONE
Growth Hormone
Polypeptide (191 Amino Acid Residues)
Specie specific
Uses cytokine receptors (JAK2 and STATs)
- STAT = Signal Transducer and Activator of Transcription
Also known as SOMATOTROPIN (STH)
Half-life = 6-20 minutes (20-50 minutes)
Plasma level higher in infants and children than adults
The activity of both Anterior and
Posterior Pituitary Gland is controlled by
the hypothalamus. The Pituitary Gland is
connected to the hypothalamus through
the INFUNDIBULUM (also called theHYPOTHALAMO-HYPOPHYSEAL STALK).
Hypothalamic neurons, present in the
hypothalamus, are connected to the
ANTERIOR PITUITARY GLAND
(Adenohypophysis) through the blood
vessels present in the stalk. To control
the Anterior Pituitary Gland, the
hypothalamic neurons utilizes chemical
agents (called HORMONES), both
Releasing and Inhibitory Hormones.
These hormones are released directly
into the circulation.
Human Growth Hormone can only promote growth to humans.
Release of growth hormones is not continuous, it released in a pulsatile manner.
After puberty, there is a marked decrease in hormone production –that is why there
is minimal growth seen in adults.
On the other hand, to control the POSTERIOR PITUITARY GLAND, the hypothalamus will now usethe neurons present in the stalk. The hypothalamus will not utilize hormones but instead, it will
generate nerve impulses. It will be the nerve impulse coming from the hypothalamus that will
affect the activity of the Posterior Pituitary -- that is why it is called Neurohypophysis, because it
is neurally controlled.
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Mechanism of Action to Promote Growth
Growth Hormone (GH) stimulates the liver to secrete IGF-1 (Insulin-like Growth Factor), which
is the major intermediary of the physiologic action of GH. In the presence of IGF-1, GH exerts
the maximum effect on the target cells Promoting growth, increasing body mass and organ
size.
IGF-1 is also known as SOMATOMEDIN
Insulin-Like Growth Factor (Somatomedin)
Regulates cellular proliferation, differentiation, and metabolism
Has autocrine, paracrine, and endocrine effects
IGF-I is the major form in adults
IGF-II is the major form in the fetus
Secreted by many tissues of the body but the predominant source is the liver
Half-life is about 12 hours
Mitogenic and have marked effects on bone and cartilage
Physiologic Actions of Growth Hormone:
Stimulates growth of human cells, most especially bones and cartilages Linear Growth
Directly affects the liver, muscles, and adipose tissue
Promotes protein anabolism, prevents protein catabolism (+) Nitrogen and phosphorus
balance
Increases lipolysis (Ketogenic Effect) and promotes use of fatty acids as energy source
Decreases rate of glucose utilization, an anti-insulin effect Diabetes
Antagonizes insulin effect on muscle and adipose Insulin resistance (Diabetogenic)
Hyperglycemic hormone
Stimulates the liver to produce IGF-1
Actions Mediated by Growth Hormone and Insulin-like Growth Factor
Control of Growth Hormone Secretion
Insulin-Like Growth Factor (IGF)
IGF-1 = promotes growth after birth
IGF-2 = promotes growth to the fetus
Also called SOMATOMEDIN
To maximize the effect of GH and IGF-1, your epiphyseal plate should still be open.
This is the reason why you see normally tall persons who are not fat.
Growth Hormones antagonize Insulin-receptors, making it insensitive to the effects of
Insulin Insulin has no effect on its target cells (adipose tissue and muscles)
DIRECT EFFECTS: Sodium Retention, Insulin Sensitivity, Lipolysis*, Protein Synthesis,
and Epiphyseal Effect
INDIRECT EFFECTS: Insulin-like Activity, Anti-Lipolytic Activity*, Protein Synthesis, and
Epiphyseal Growth
When you have IGF-1, you enhance the growth promoting action of Growth Hormone.
*IGF somehow antagonizes the direct effect of GH.
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Factors Promoting Growth Hormone Release (Episodic):
Deficiency of energy substitute
- Hypoglycemia (Glucagon)
- Exercise
- Fasting
Increase in plasma level of amino acids
- Protein meal
Stressful stimuli - Fever
NREM Sleep - (SWS) DEEP SLEEP
Hormones of puberty (Androgens and Estrogens)
Ghrelin – coordinates food intake with growth
Apomorphine and L-Dopa
Norepinephrine and α-adrenergic agonists
Β-adrenergic antagonists
Factors Inhibiting Growth Hormone Release:
Hyperglycemia
Lack of exercise
Increase in plasma free fatty acids
Chronic intake of steroids
REM Sleep – (FWS) LIGHT SLEEP
Somatostatin
Increase level of Somatomedin and Growth Hormone
α-adrenergic blockers
β-adrenergic agonists
Serotonin agonists
Growth Hormone Release:
Presents diurnal rhythm
Stimulated during deep sleep
Peak secretions before midnight and in the early morning
Secretion is pulsatile
Important Hormones in Human Growth:
Growth Abnormalities:
Gigantism
(Picture on the Lower Right of the Previous Page) CONTROL OF GROWTH HORMONE
SECRETION
Growth Hormone is controlled via the Negative Feedback Mechanism (Endocrine Driven
Axis Feedback).
The hypothalamus will secrete Growth Hormone Releasing Hormone (GHRH) so that the
Anterior Pituitary Gland will be able to release Growth Hormone.
When Growth Hormone is released, it will stimulate the liver to produce IGF-1 to
maximize the action of the Growth Hormone on the target organs. When there is already an increased amount of IGF-1, since this is controlled by the
negative feedback mechanism, the increased amount of IGF-1 will cause inhibition of the
activity of the Anterior Pituitary Gland – this is to lessen the production of Growth
Hormone and to lessen the effects on the target cells.
The increase in the amount of IGF-1 will not only inhibit the activity of the Anterior
Pituitary gland but will also affect the hypothalamus by stimultaing it to produce
Somatostatin (or the Growth Hormone Inhibiting Factor) which will eventually inbihit the
Anterior Pituitary Gland to produce Growth Hormone.
There will be DUAL INHIBITION – inhibition in the Pituitary Gland and in the
Hypothalamus.
Excessive Growth Hormone in the plasma can also cause inhibition to the hypotalamus.
Negative Feedback Mechanism:
Long Feedback Loop
- Liver Pituitary Hypothalamus- Excess IGF-1
Short Feedback Loop
- Excess Growth Hormone
Among the amino acids, ARGININE is the most effective in stimulating the Growth
Hormone.
During Puberty, there is sudden increase in height. During this time, sex hormones
increase in the body.
Earlier Increase in Height FEMALES
Greater Increase in Height MALES
Those who are Asthmatic and are under Steroid Management usually does not attain a
normal height.
(Picture Above) IMPORTANT HORMONES IN HUMAN GROWTH:
Hormones that Presents a Synergistic Effect with GH:
T3 T4 High during childhood years Somatotropin (STH)
Androgens, Estrogens Only observed during puberty
Insulin
(Picture Above) Excessive Growth Hormone before puberty results to GIGANTISM. It occurs
when the epiphyseal plate is still open.
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Acromegaly
Other Growth Abnormalities:
Tall Stature (Endocrine Disorders)
- Sexual Precocity Early Onset of Estrogen/Androgen Secretion
- Thyroxicosis But if left untreated height will eventually decrease
Tall Stature (Non-Endocrine Disorder)
- Cerebral Gigantism (Soto’s Syndrome)
- Marfan’s Syndrome
- Homocystinuria
- Beckwith-Wiedemann Syndrome - XYY Syndrome
- Klinefelter’s Syndrome
Pre-Pubertal Growth Hormone Deficiency
- Tumor causing hypopituitarism (decreased hormonal output)
Pituitary Dwarfism
- Body is normally proportioned
- Normal intelligence
- Normal life span
Panhypotituitarism
- Adenohypophyseal hormones are deficient
Post-Pubertal Growth Hormone Deficiency -- ?
- Now recognized as pathological
- Growth is not impaired
- Metabolic problems Hypoglycemia
- Amout of fat in the body increases
- Amount of protein decreases- Muscle weakness and early exhaustion
Dwarfism (Endocrine Disorders)
- Laron Dwarfism – GH insensitivity due to a defect in GH receptors and a marked decrease in
IGF-1
- African Pygmies – IGF-1 fails to increase at the time of puberty; partial defect in GH receptors
- Glucocorticoid excess
- Cretinism – Thyroid Hormone Deficiency
(Picture Above) PROBLEMS EXPERIENCED BY PERSONS WITH ACROMEGALY
Glucose metabolism Diabetes
Vision Tunnel Vision
Muscles Alteration in protein anabolism
Enlargement of distal body parts (hands, feet, face, jaw)
Jaw increase in size + Number of teeth remains the same Teeth are separated
Prominent forehead Frontal Bossing
Prominent jaw Prognathism
Most of the time, Acromegalic persons die due to diabetes.
(Picture Above) EXCESSIVE/INCREASE IN GROWTH HORMONE
Early Onset (Before Puberty) GIGANTISM
Late Onset (After Puberty) ACROMEGALY
During Puberty ACROMEGALIC-GIGANTISM
Severe injury in the Pituitary Gland
Common Cause: Difficult delivery Massive blood loss
- Pituitary Gland is a highly vascularized organ They need blood- If there is sudden blood loss Decrease in blood volume Necrosis of the
Pituitary Gland SHEEHAN’S SYNDROME Can cause PANHYPOPITUITARISM
? because before, this was not considered as a problem During post-puberty, you
have already reached your adult height
Now recognized as pathological Metabolic effects of Growth Hormone is lost
Both Laron Dwarfism and African Pymies have normal Growth Hormone, the problem
lies in the receptors. Remember that if there’s a problem with your receptors, the
hormone will be less effective.
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Dwarfism (Non-Endocrine Disorders)
- Malnutrition
- Syndromes of short stature (Turner’s)
- Autosomal Chromosomal Disorders (Down’s)
- Chronic Cardiac/Pulmonary Disorders
- GI/Hepatic/Renal Disorders
- Achondroplasia – Autosomal dominant condition wherein there is alteration in fibroblas
growth factor receptor
- Kaspar-Hauser Syndrome – pyschosocial dwarfism; seen in neglected and chronically abusedchildren
B. MELANOCYTE STIMULATING HORMONE (MSH)
Melanocyte Stimulating Hormone (MSH)
Stimulates the melanocytes to produce melanin Evenly distributed
Adrenocorticotropic Hormone (ACTH) = Hormone with melanocyte stimulating effect- When present in excessive amount in the blood, skin pigmentation occurs
Abnormal Skin Pigmentation/Lack of Pigmentation
Albinism – congenital absence of melanin
Piebaldism – congenital defect characterized by patches of skin that lacks melanin
Pituitary Failure (Hypopituitarism)
Decrease in the secretion:
- Gn (FSH/LH) Mild cases
- TSH Mild to moderate
- ACTH Moderate to severe
- GH (STH) Severe cases
II. POSTERIOR PITUITARY GLAND (NEUROHYPOPHYSIS)
Neurohypophyseal Hormones
Produced as prehormones
Cosecreted with a peptide – Neurophysin
Neurophysin I = associated with ADH
Neurophysin II = associated with Oxytocin
A. ANTI-DIURETIC HORMONE (ADH) or ARGININE VASOPRESSIN (AVP)
Anti-Diuretic Hormone (ADH) or Arginine Vasopressin (AVP) Short polypeptide, 9 Amino Acid residue
Uses the following receptors:
- V1a and V1b = Vasoconstrictive Effects (PI Ca++)
- V2 = Anti-Diuretic Effects (G-Protein cAMP)
Half-life = 15-20 minutes
Essential for water balance
Affects facultative water reabsorption in the kidneys [Late Part of the Distal Convoluted Tubules
and Cortical Collecting Ducts] (Water channels – AQP2)
Excitatory Stimuli for ADH Release:
Increase Effective PCOP (OPPP)
- 1% increase in plasma osmolarity
Dehydration (Nausea, Vomiting, Diarrhea)
Hypovolemia
- 5-10% decrease in blood volume Pain
Emotion
Stress
Exercise
Warm/Hot Environment
Standing
Angiotensin
Nicotine, Clofibrate, Carbamazepine
Inhibitory Stimuli for ADH:
Decrease effective PCOP (OPPP)
Overhydration
Hypervolemia
Alcohol Intake
Cool/Cold Environment
Regulation of Secretion and Actions of ADH:
Before, they say that there is such thing as “Melanocyte Stimulating Hormone (MSH),” and
say that it is responsible for skin pigmentation. But now they found out that there is none.
Now, they say that the one stimulating the melanocytes to produce melanin is having a
normal amount of Adrenocortitropic Hormone (ACTH). ACTH has a melanocyte stimulating
effect.
Degree of pigmentation does not depend on the amount of ACTH, depends on
the number of melanocytes present in your skin
Lighter Skin: melanocytes
Darker Skin: melanocytes
Melanocytes protects the skin from UV rays
melanocytes More prone to skin cancer
ACTH will have a different effect on the body with regards to pigmentation
There will still be pigmentation, but it is not evenly distributed
Your skin is not the only one affected, even your mucosa is affected
Degree of severity of injury in the Pituitary Gland depends on the activity of the Anterior
Pituitary Gland, particularly to the amount of secretions.
Receptors for plasma osmolality
Located in the OrganumVasculosum of the Lamina
Terminalis
Volume sensitive receptors
Located in the Subfornical Organs
Thirst Center Superolateral
Part of the Hypothalamus,
specifically in the median preoptic
nucleus
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Pituitary Hyposecretion/Absence of ADH
Poluria – large volume of diluted urine
Polydipsia
Central Diabetes Incipidus
Nephrogenic Diabetes Insipidus
Polyuria and polydipsia
A congenital defect in the V2 receptors (90%), some cases are due to mutations in the AQP2
gene
X-linked Normal neurophysis
Inability of the Distal Collecting Tubules and Collecting Ducts to react to ADH
SIADH – Syndrome of “Inappropriate” Hypersecretion of ADH
Excess ADH (ectopic/hypothalamic) is causing dilutional hyponatremia and loss of salt in the
urine
Blood is hypotonic whereas urine is hypertonic
Could be seen in patients with cerebral disease and pulmonary disease (oat cell lung carcinoma)
Nephrogenic Syndrome of Inappropriate Antidiuresis
Plasma hypotonicity, hyponatremia with hypertonic urine
Mutation of the V2 receptor gene Receptor is activated even in the absence of ADH
Plasma ADH is very low
Hypersecretion of ADH
Seen in some patients after surgery because of pain and hypovolemia Low plasma osmolality
and dilutional hyponatremia
If observed in patients after surgery, monitor closely fluid intake because high fluid intake can
cause water intoxication
B. OXYTOCIN Oxytocin
Short polypeptide, 9 Amino Acid residues
Synthesized mostly by the paraventricular nucleus (hypothalamus)
Uses G-protein coupled serpetine receptors which can increase intracellular calcium levels
Excitatory Stimuli
Major stimulus for Oxytocin release is stimulating the nipple (breast) Release of milk
Suckling of the nipple + Prolactin secretion
Other stimuli are mechanical stimulation of the body especially those body parts associated
with the reproductive system
Psychogenic stimuli can also stimulate release
In pregnancy, release increases after parturition has begun
Release increase progressively during parturition
Increase frequency and duration of uterine action potentials Increasing strength and
frequency of uterine contractions
Estrogen enhances the effect of Oxytocin by reducing the membrane potential of uterine
smooth muscles, lowering the threshold for stimulation (increase the number of Oxytocin
receptor mRNA in the uterus)
Uterine effects – inhibited by progesterone
Stimulates the myoepithelial cells of the breast Milk-let down reflex
Effects of Oxytocin
Major Effects:
- Milk ejection in lactation
- Induction of parturition
Minor Effects:
- Control of Estrous Cycle
- Ovarian Steroidogenesis
- Testicular Steroidogenesis
- Male Ejaculation
- Body osmolarity (Effective Natriuretic Agent)
- Lipogenesis
No problem with ADH, the problem lies with the Distal Convoluted Tubules and Collecting
Ducts. V2 receptors are activated, allowing water to be reabsorbed even without ADH.
Usually happens after long surgical procedures Tendency to have a response to secrete
excessive ADH Results to Low Plasma Osmolality and Dilutional Hyponatremia Fluid
intake must be monitored
When nursing mothers hear their baby’s cry Produce Oxytocin
Estrogen = increases the number of Oxytocin receptors
During pregnancy, your Estrogen increases
“Estrogen-Priming of the Uterus”
Torender the uterus more sensitive to Oxytocin during end of pregnancy
Only responsible for the milk release. Milk production is the responsibility of Prolactin.
Oxytocin released during coitus:
When the male ejaculates, sperm does not go directly into the uterus, it is deposited
into the cervical wall The contraction of the uterus during coitus acts as a vacuum
trying to help the sperm move up to the upper portion of the uterus so that
fertilization will occur
“Oxytocin stimulating the uterus to contract is providing a free escalator ride for the
sperm”