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Pathophysiology II
Exam 2 - Lecture (Neuroendocrine Pituitary)
21
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Not Applicable
03/05/2008

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Term
What is the Metabolic Clearance Rate?
Definition

- Defines the quantitative removal of hormone from plasma

- The bulk of hormone is cleared by liver and kidneys

- Only a small fraction is removed by target tissue. 
    - Protein and amine hormones bind to receptors           and are internalized and degraded

    - Steroid and thyroid hormones are dgraded after       hormone-receptor complex binds to nuclear               chromatin 

Term
MCR of some hormones
Definition

[image]- Amines 2-3 minutes

- Thyroid Hormones  T4 6.7 days
                             T3 0.75 Days

- Polypeptides 4-40 minutes

- Protines 15-170 minutes

- Steroids 4-120 minutes 

Term
What is a Hormone-Receptor interaction?
Definition

- A protein that binds a ligand with high affinity and low capacity.

- A tissue becomes a target for a hormone by expressing a specific recetpor for it.  Hormones circulate in the blood stream but only cells with receptors for it are targets for its action   

Term
Why are second Messenger systems needed?
Definition

- Hormones that are not lipophillic will not permeate the target cell, so they need messengers to do it for them.

- Receptors for the water soluble hormones are found on the surface of hte target cell, on the plasma membrane.  These types of receptors are coupled to various second messenger systems which mediate the action of the hormone in the target cell. 

- Chnages evoked by the actions of second messengers are usually rapid. 

Term
Receptors for lipid-soluble hormones reside within the cell
Definition

- These hormones can diffuse through the lipid bilayer of hte plasma membrane, their receptors are located on the interior of the target cell. 

- Diffuses into the cell and binds to the receptor which undergoes a conformational change.  The receptor-hormone complex is then binds to spcidfic DNA sequences called response elements.  

- These DNA sequences are in the regulatory regions of genes. 

Term
Receptors for lipid-soluble hormones reside within the cell (Part II)
Definition

- The receptor-hormone complex binds to thhe regulatory region of the gene and changes the expression of that gene. 

- In most cases the binding of recpetor-hormone complex to the gene stimulating the trancription of messenger RNA.  

- The messenger RNA travles to the cytoplasm where it is translated into protein.  The translated proteins that re produced participate in the response that is evoked by the hormone in the target cell.  

- Responses evoked by lipid soluble hormones are usually SLOW, requiring transcription/translation to evoke physiological responses 

Term

Receptor Control Mechanisms

 

Definition

- Hormonally induced negative regulation of receptors is referred to as homologous-desensitization.

- This homeostatic mechanism protects from toxic effects of hormone excess.

- Heterologous desensitization occurs when exposure of the cell to one agonist reduces the responsiveness of the cell any other agonist that acts trhough a different receptor.  

- This most commonly occurs through receptors that act through the adenylyl cyclase system.   

Term
Mechanisms of endocrine disease
Definition

- Endocrine disorders result from hormone deficiency, hormone excess or hormone resistance.

- Almost without exception, hormone deficiency causes disease 

    - One notable exception is calcitonin deficiency 

Term
Mechanisms of endocrine disease (Part II)
Definition

- Deficiency usually is due to destructive process        occurring at gland in which hormone is produced -   infection, infarction, physical compression by tumor growth, autoimmune attack

     - Type I Diabetes 

Term
Mechanisms of endocrine disease (Part III)
Definition
- Deficiency can also arise from genetic defects in hormone production - gene deletion or mutation, failure to cleave precursor, specific enzymatic defect (steroid or thyroid hormones)
- Congenital Adrenal Hyperplasia 
- Inactivating mutations of receptors can cause hormone deficiency
    - Testicular Feminization Syndrome
- Hormone excess usually results in disease
- Hormone may be oerproduced by gland that normally secretes it, or by a tissue that is not an endocrine organ.  
- Endocrine gland tumors produce hormone in an unregulated manner.
    - Cushing's Syndrome 
- Exogenous ingestion of hormone is the cause of hormone excess - for example, glucocorticoid excess or anabolic steroid abuse.
- Malignant transformation of non-endocrine tissue causes dedeifferentiation and ectopic production of hormones
- Anti-receptor antibodies stimulate receptor instead of blocking it, as in the case of the common form of hyperthyroidism.   
- Alterations in receptor number and function result in endocrine disorders.
- Most commonly, an abberant increase in the level of a specific hormone will cause a decrease in available receptors
    - Type II Diabetes 
Term
Hypothalamus and Pituitary Unit
Definition

- The hypothalamus-pituitary unit is the most dominanat portion of the entire endocrine system.

- The output of the hypothalamus-pituitary unit regulates the function of the thyroid, adrenal and reproductive glads and also controls somatic growth, lactation, milk secretion and water metabolism.

- Pituitary function depends on the hypothalamus and the anatomical organization of the hypothalamus-pituitary unit reflects this relationship.  - THe pituitary gland lies in a pocket of bone at the base of the brain, just below the hypothalamus to which it is connected by a stalk containing nerve fibers and blood vessels.  The pituitary is composed to twolobes -- anterior and posterior.    

Term
Posterior Pituitary: Neurohypophysis
Definition

- Posterior Pituitary: An outgrowth of the hypothalamus composed of neural tissue.

- Hypothalamic neurons pass through the neural stalk and end in the posterior pituitary 

- The upper portion of the neural stalk extends into the hypothalamus and is called the median eminence.  

- Midsagital view illustrates that magnocellular neurons paraventricular and supraoptic nuclei secrete oxytocin and vasopressin directly into capillaries in the posterior lobe.   

Term
Anterior Pituitary: Adenohypophysis
Definition

- Connected to the hypothalamus by the superior hypophyseal artery. 

- The anterior pituitary is an amalgram of hormone producing glandular cells.

- The anterior pituitary produces six peptide hormones 

Term
Anterior Pituitary Hormones produced
Definition

- Prolactin (PRL)

- Growth Hormone (GH)

- Thyroid stimulating hormone (TSH)

- Adrenocorticotropic hormone (ACTH)

- Follicle-stimulating Hormone (FSH)

- Luteinizing Hormone (LH) 

Term
Hypothalamus and Anterior Pituitary Relationship
Definition
- Neurosecretory cells secrete releasing factors into capillaries of the pituitary portal system at the median eminence which are then transported to the anterior pituitary gland to regulate the secretion of pituitary hormones. 
Term
Where do Hypothalamic releasing factors for anterior pituitary hormones go?
Definition

- Travel to adenohypophysis via hypophyseal-portal circulation.

- Travel to specific cells in anterior pituitary to stimulate synthesis and secretion of trophic hormones 

Term
Characteristics of hypothalamic releasing hormones
Definition

- Secretion in pulses

- Act on specific membrane receptors

- Transduce signals via second messengers

- Stimulate release of sotred pituitary hormones

- Stimulate synthesis of pituitary hormones

- Stimulates hyperplasia and hypertropy of target cells

- Regulates its own receptor. 

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