[PhysioB] Endocrine Physiology Part 2 - Pituitary Gland - Dr. Barbon (Lea Pacis)

8/12/2019 [PhysioB] Endocrine Physiology Part 2 - Pituitary Gland - Dr. Barbon (Lea Pacis)

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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.





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.





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.





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.





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





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”

[PhysioB] Endocrine Physiology Part 2 - Pituitary Gland - Dr. Barbon (Lea Pacis)

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