HYPOTHALAMUS AND PITUITARY GLAND (Video 2)

Endocrinology Exam 1

Hypothalamus is part of the

DIENCEPHALON

Pituitary gland has 2 main parts:

1. Anterior lobe (adenohypophysis)

2. Posterior lobe (neurohypophysis)

(SELLA TURCICA)

Encapsulated by a cavity in the sphenoid

bone

• This is where the pitutary Gland is housed

HYPOTHALAMIC NUCLEI (2)

Hypothalamus consists of HYPOTHALAMIC NUCLEI (clusters of neuron

cell bodies) that each have a specific name

1. Paraventricular nucleus

2. Supraoptic nucleus

Hypothalamus & Posterior Pituitary Hormones (2)

1) ADH
2. OXYTOCIN

ADH or Vasopressin

• Protein Hormone

• Made in the hypothamus and secreted out of the posterior pituitary

• supraoptic nucleus

.

• Increased plasma osmolality is the most important physiologic stimulus for increasing ADH secretion

• This makes one pee less

Hypovolemia

Volume contraction (e.g., due to hemorrhage), is also a potent stimulus for ADH secretion.

• Decreases in extracellular fluid (ECF) volume of 10% or more cause a significant decrease in arterial blood pressure that leads to ADH secretion

ADH Blood pressure graph

Factors Affecting ADH Secretion

Primary Actions of ADH

The primary action of ADH is water reabsorption by the kidneys.

• This results in an increase in urine osmolality and a decrease in urine volume.

.

The cellular effect occurs in principal cells of the late distal convoluted tubule and collecting duct (tubule) when ADH binds to V2 receptors causing the insertion of aquaporin‐2 channels, thereby increasing water permeability.

Secondary Actions of ADH

The secondary action of ADH is contraction of arteriolar vascular smooth muscle via binding to V1 receptors, thereby causing vasoconstriction and increased BP.

Neurogenic (Central) Diabetes Insipidus

• decreased ADH secretion

Nephrogenic Diabetes Insipidus

Renal insensitivity to ADH due to a defect in the V2 receptor or cell signaling process

.

In adults, the major clinical manifestations of diabetes insipidus include:

• The frequent passage of large volumes of dilute urine (specific gravity below 1.005 and a urine osmolality less than 200 mmol/kg/24 hr)

• Excessive/intense thirst (particular predilection for cold or iced drinks)

• Increased fluid ingestion

Primary Polydipsia

compulsive water drinking or Dipsogenic Diabetes Insipidus

ADH (Vasopressin) Drug Example:

Desmopressin (DDAVP)

Desmopressin (DDAVP)

• Synthetic ADH

Indicated ONLY for neurogenic (central) diabetes insipidus

Desmopressin has potent anti‐diuretic activity but much less vasoconstrictive activity

Nasal‐spray formulation → older

Oral tablet → released in the US in 1995

The tablet is available in 0.1 mg and 0.2 mg sizes.

The oral form has about one‐tenth to one‐twentieth the potency of the nasal form because only about 5% is absorbed from the intestine

Additional indication: Primary nocturnal enuresis (but not less than 6 yrs old)

Treatment of Nephrogenic Diabetes Insipidus (5)

Structural Differences between Vasopressin vs Oxytocin

• Very Similarly Structurally (Oxytocin has Leucine and lle that ADH does not)

Oxytocin (Two Targets)

1. Mammary Glands

2. Uterus

Posterior Pituitary Hormones: Oxytocin & Lactation

Stimulation of the nipple through suckling produces a neurohumoral reflex that causes secretion of oxytocin.

• In turn, oxytocin causes contraction of the myoepithelial cells of the mammary alveoli & ducts and the ejection of milk.

Posterior Pituitary Hormones: Oxytocin & Birth

Oxytocin affects the myometrium, as it increases both the frequency and the

duration of action potentials during uterine contractions.

• Thus, administration of oxytocin initiates contractions in a quiescent uterus and increases the strength and frequency of muscle contractions in an active uterus.
  Positive Feedback

Are there any pathophysiological conditions associated with oxytocin?

None really to speak of…….although synthetic

oxytocin (Pitocin) is used to induce or attenuate labor in

pregnant females needing assistance

What about oxytocin in males? Does oxytocin have other

functions in males and females?

Cuddle hormone”, “bonding hormone”, “love hormone”

• Facilitation of trust

• Antidepressant‐like effects

• Promotes feelings of empathy

Oxytocin Preparations (Example)

Pitocin

Pitocin (2)

Indicated for:

1. Induction or enhancement of uterine contractions during labor

2. Prevention of postpartum uterine hemorrhage

.

Nasal‐spray formulation available in Europe → used a few minutes prior to breast‐feeding to stimulate/enhance lactation reflex

Cell types of the anterior pituitary mnemonic (5)

Tom

Cruise

Smells

Like

Gumbo

Cell types of the anterior pituitary (5)

1. Thyrotropes

2. Corticotropes

3. Somatotropes

4. Lactotropes

5. Gonadotropes

The remaining cell types in the anterior pituitary are non‐ hormone producing cells (i.e., connective tissue, etc.)

Thyrotropes

(5%) TSH

• TSH

• Thyroid-stimulating hormone

Corticotropes

(15%) ACTH

• Adrenocorticotropic hormone (ACTH)

Somatotropes

(20%) GH

• Growth Hormone

Lactotropes

(15%) Prolactin

Gonadotropes

(15%) FSH, LH

Anatomic Relationships: Hypothalamus & Anterior Pituitary

The secretion of the 6 different hormones from the anterior pituitary

are influenced by the secretion of 6 different hormones (the

presence of a “PRF” has not been supported) from the hypothalamus

Regulation of GH Secretion

The main regulators of GH secretion are the

hypothalamic hormones GHRH and GHIH (otherwise known as somatostatin)

Direct Effects of GH Secretion

Some of the actions of growth hormone result from the hormone's direct effect on target tissues such as skeletal muscle, the liver, or adipose tissue.

Direct Effects of GH Secretion

Other actions of growth hormone are mediated indirectly through

the production of SOMATOMEDINS (or INSULIN‐LIKE GROWTH

FACTORS [IGFs]) mainly from the liver, but also from skeletal muscle,

bone and kidneys.

.

Also notice the numerous negative feedback mechanisms shown in the diagram above.

Physiological Functions of GH (Bones)

In growing bones, the epiphyseal plates widen and more bone is laid down at the ends of long bones.

Glucose Sparing Effect

• Physiological Functions of GH

Diabetogenic Effect

Growth hormone decreases glucose uptake and utilization by target tissues such

as muscle and adipose tissue.

Acromegaly (Example)

Acromegaly Symptoms

Acromegaly Symptoms pt 2

DENTAL ASPECTS OF ACROMEGALY (First Reason)

Enlarged tongue (MACROGLOSSIA) with indentations of lateral borders due to pressure against the teeth

DENTAL ASPECTS OF ACROMEGALY (Second Reason)

Enlarged prognathic mandible (prognathism)

DENTAL ASPECTS OF ACROMEGALY (Third Reason)

Malocclusion

Normal Occlusion

Malocclusion

A problem in the way the upper and lower teeth fit together in biting or chewing

.

3 Types

Class 1 Malocclusion

Class 2 Malocclusion

• Over Bite

Class 3 Malocclusion

• Underbite

DENTAL ASPECTS OF ACROMEGALY (4th Reason)

Spacing in the teeth

Other oral manifestations OCROMEGALY (4)

1. Thick lips

2. Salivary gland enlargement

3. Thickening and folding of facial skin

4. Enlarged nasal sinuses

.

Overall, acromegalic patients may report to the dentist

with complaints of malocclusion, difficulty in speech due

to an enlarged tongue, mobility of teeth or missing teeth.

Acromegaly & GH can be used as a

Performance Enhancing Drugs

GHIH (Somatostatin) Preparations (Examples)

1. Octreotide (Sandostatin)

2. Lanreotide

• Indicated for acromegaly

Growth Hormone Receptor Antagonists

Example: Pegvisomant

.

Indicated for acromegaly

.

Blocks growth hormone receptors throughout the body and reduces blood levels of IGF‐1

Pituitary Dwarfism

• GH Deficiency

DENTAL ASPECTS OF GH DEFICIENCY

Permanent teeth and their roots show a delayed pattern of eruption

.

Maxilla and mandible are smaller than normal (“small facial appearance” for age)

.

Dental arches are smaller than normal and therefore cannot accommodate all the teeth resulting in crowding and malocclusion

.

Decrease in salivary flow due to hypofunctioning of salivary glands which leads to increased caries and periodontal disease

Growth Hormone Preparations

GH preparations are aqueous solutions of GH for subcutaneous administration to treat growth hormone deficiency.

1. Genotropin

2. Humatrope

3. Norditropin

4. Nutropin

5. Protropin

6. Saizen

Most are available in multiple‐dose pen devices which significantly

aid in administration.

Pituitary Gigantism

Basically, a somatotropic adenoma………..

Regulation of Prolactin Secretion

In persons who are not pregnant or lactating, prolactin secretion is tonically inhibited by dopamine (prolactin‐inhibiting hormone, PIH) from the hypothalamus.

• Pregnancy and breast‐feeding are the most important stimuli for prolactin secretion

Physiological Effects of Prolactin

PRL stimulates milk production in the postpartum period.

• During pregnancy, PRL secretion increases and, in concert with many other hormones (estrogen, progesterone, insulin and cortisol), promotes additional breast development in preparation for milk production.

Physiological Effects of Prolactin (Female)

In females, prolactin inhibits ovulation by inhibiting the synthesis and

release of GnRH.

.

Inhibition of GnRH secretion and, secondarily, inhibition of ovulation

account for the decreased fertility during breast‐feeding.

Physiological Effects of Prolactin (Male)

In males with high prolactin levels (HYPERPROLACTINEMIA) (e.g., due

to a PROLACTINOMA), there is a parallel inhibitory effect on GnRH

secretion and spermatogenesis, resulting in infertility. There is also

GYNECOMASTIA and GALACTORRHEA

• Prolactin in your blood

• Becomes cancerous PROLACTINOMA

Drugs for Hyperprolactinemia

Dopamine Agonists (mimic dopimine):

• Cabergoline (Cabaser, others)

• Bromocriptine (Parlodel, others)

.

1. Indicated for prolactinoma

• Mimic the action of dopamine (PIH)

Pituitary Adenoma & Vision

Bitemporal Hemianopsia or Hemianopia

• Causes tunnel vision if there is a tumor in the pituitary gland

TRH Pathway (4)

TRH →

TSH →

Thyroid Gland →

T3 & T4

CRH Pathway (4)

CRH →

ACTH →

Areadenal Cortex →

Cortisol

GHRH & GHIH Pathway(3)

GHRH (+) & GHIH(-) →

GH →

Many Target Tissues

PRH & PIH Pathway (3)

PRH (+) & PIH (-) →

Prolactin →

(Breast Tissue)

Four Trends in Growth Charts (Growth Hormone related)