Biology 2402  A&P     Endocrine System  
Dr. Weis                 

ENDOCRINE SYSTEM

Classic Glands (PTA= 3P,2T,1A)

Other organs with endocrine function include:

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Endocrine system has ties to and works with the Nervous and Immune systems in order to maintain homeostasis.

Hormones

Chemicals secreted in small amounts from ductless glands and released into circulation to have their affects on other organs. Organs may belong to same system or another system.  If hormones affect organs within the same system, they are local hormones known as paracrines.
NOTE: The use of the term "cytokines" should be reserved for the immune system chemical communication mechanisms.

Classified chemically :

Hormones will influence the activity of certain cells :: 

Target cells, due to the presence of specific receptors.

Alter cell activity by causing changes in:                                                    

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Therefore, all cells are exposed to hormones.  The specific receptor determines the cell's activity to bind the hormone and creating a receptor hormone complex, called the HRC. This is a chemical fit and must happen to create a signal that sends the message.  This signaling is called signal transduction.

Two Signal transduction mechanisms of action [MOA] are involved after the hormone has bound to the receptor::

For receptors located on the membrane: Formation of secondary messengers :  cAMP, Ca++, cGMP, tyrosine kinase (TK)

For receptors located inside the cell: Direct gene (DNA) activation

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Secondary Messenger System

Used by peptide and polypeptide hormones and most single amino acid hormones.  These hormones (first messenger) bind to cell membrane receptors and exert effects through secondary messengers created or released in the cell such as cyclic AMP (cAMP) , Calcium ion (Ca++), or cyclic GMP (cGMP), TK.

Binding to the receptor coupled to a G protein as an intermediary causes activation of an amplifier enzyme.

Specific Examples of Secondary Messenger Systems:: 

A) Adenyl cyclase activated  by GTP --> GMP, in the G protein.  This activated enzyme causes the conversion of ATP to cAMP.  cAMP then activates protein kinases whose main action is to add a phosphate group to different proteins.  The result is the activation or inhibition of these proteins.  cAMP is then degraded by phosphodiesterase (PDE) in the cytoplasm.

B) G protein activates phospholipase C to split PIP into diacylglycerol (DAG) and inositol triphosphate (ITP) that act as secondary messengers.  Diacylglycerol activates protein kinase C and can trigger the opening of Ca++ channels.   Ca++ enters from ECF and can then act as a secondary messenger and will bind to its protein calmodulin.  This binding can activate other enzymes.    Inositol triphosphate triggers calcium release from the smooth endoplasmic reticulum.  This calcium can then act as a third messenger and will bind to its protein calmodulin to then cause activation of certain enzymes, or increase the response of other hormones.

C) Inhibitory mechanisms for Secondary Messengers:: Other G proteins (inhibitory G proteins) when activated  can reduce the levels of secondary messengers and stimulate their removal by other enzymes.  This is seen when an inhibitory G protein activates phosphodiesterase [PDE] to help degrade cAMP to AMP.

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Signal Transduction for hormone receptors located in the cell:

Direct Gene Activation

The plasma membrane of the cell is a phospholipid and is lipid soluble.  Steroids and single amino acids will be able to diffuse through the cell membrane to bind to receptors located within the cell.  This hormone-receptor complex interacts with nuclear chromatin at specific DNA regions.  This binding can activate  the genes to start DNA transcription of messenger RNA and translation will result in protein synthesis or this binding can inactivate and therefore decrease the rate of transcription.  This is especially seen with metabolic rates involving thyroid hormones.

Direct gene activation is slower in onset than those messenger systems used by proteins. The delay may be hours to days.

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Hormones are very potent chemicals at low blood levels, have short half lives

(t 2 = 1 to 30 minutes), target organ response can be minutes to days.

Control of release: Through negative feedback mechanisms called Endocrine Reflexes.

This stimulus for hormone release can be

The nervous system can override normal endocrine controls primarily by way of the Hypothalamus and its control over the pituitary gland. Recall that the hypothalamus has several nuclei to regulate the functions which include:

The hypothalamus is in the region of the brain called the diencephalon, located below the thalamus.  In this region, during embryological development, the neural ectoderm of the diencephalon forms a diverticulum called the infundibulum which will gravitate downward to form the nervous portion of the pituitary gland. 

From the oral ectoderm of the primitive mouth, a diverticulum known as Rathke's Pouch grows upward toward the brain to form the glandular portion of the pituitary.  These two diverticulum will come in contact and will eventually become the pituitary gland that is located in the sella turcica of the sphenoid bone.

The pituitary is therefore two different tissues::

These two lobes of the pituitary can also be named based on anatomical references:

             the anterior lobe or anterior pituitary (AP)

             the posterior lobe or posterior pituitary (PP).

The adenohypophysis (AP) consists of the :

The neurohypophysis (PP) consists of the :

The pituitary is connected to the hypothalamus by way of the pituitary stalk that is formed from the pars tuberalis and the infundibular stem.  Around the stalk are blood vessels that supply both parts of the pituitary individually and are named the posterior pituitary artery & vein and the anterior pituitary artery & vein. Hormones secreted from each area of the pituitary enter their own individual blood supply to eventually be delivered to the heart and then sent to the rest of the body tissues.

Because the pituitary consists of two different tissues, the Hypothalamus has to maintain control over the pituitary by two different means :

Neurons whose cell bodies are located in the hypothalamus are involved in secreting peptide hormones.  Their unmyelinated fibers have a pathway through the median eminence and pituitary stalk and will end on the basement membrane of capillaries from the inferior pituitary artery that supplies the posterior pituitary.  These hypothalamic neurons, the supraoptic and paraventricular, can secrete one of two peptide hormones:

             antidiuretic hormone (ADH), or also called arginine vasopressin (AVP)

             oxytocin (OT)

These hormones are formed in the neuron cell body and travel by axonal flow down the nerve fibers by way of a protein carrier (neurophysin) and will be stored in the nerve endings, to be released upon stimulation of the particular hypophyseal neuron, and then this neuropeptide can be carried through the blood system.

Therefore, the posterior pituitary has close direct anatomical association with the hypothalamus due to its neural connections. The nerve fiber tracks and axon terminals form the hypothalamic hypophyseal track and are supported by pituicytes, the cells of the posterior pituitary.

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Hypothalamic Control over the Anterior Pituitary

The hypothalamus has no direct neural connection to the anterior pituitary, but has connections through the blood supply from the superior pituitary artery.  This vessel will break into two capillary plexuses. 

The primary plexus is located near the median eminence and surrounds the axonal ends of the tuberinfundibular neurons located in the ventral hypothalamus. The secondary plexus surrounds the anterior pituitary lobe.  The two plexuses are connected by small hypophyseal portal veins and this whole system becomes the hypophyseal portal system and provides a vascular connection between the anterior pituitary and the hypothalamus.......How ?  

     The tuberinfundibular neurons in the median eminence secrete releasing or inhibitory peptide hormones.  (releasing hormone or RH, inhibitory hormone or IH).  These hormones go into the primary plexus through the fenestrations in the capillary wall, then into the portal circulation, and then secondary plexus that surrounds the anterior pituitary (AP).  These RH or IH affect the AP by regulating its hormone producing cells.

Some Hypothalamic factors :

CRH..........      corticotropin releasing hormone

GnRH.........     gonadotrophic releasing hormone

TRH..........       thyrotropic releasing hormone

GHRH........     growth hormone releasing hormone

GHIH.........      growth hormone inhibitory hormone (also called somatostatin)  

PIH.........         prolactin inhibitory hormone (also called Dopamine)

PRH.........       prolactin releasing hormone

Therefore.......the posterior pituitary STORES the hormones of the hypothalamus, and the anterior pituitary responds by releasing or stopping its hormones under the direction of the hypothalamic factors, -RH or -IH.  Thus, the anterior pituitary cells become the target cells for the hypothalamic factors. 

The various cell types of the AP are :

So the anterior pituitary hormones are :

1. Growth hormone (GH)  {also called somatotrophin}

2. Thyroid stimulating hormone (TSH)  {a.k.a.  Thyrotrophin}

3. Adrenocorticotrophic hormone (ACTH)  {corticotropin}

4. Gonadotropins : regulate function of gonads

Follicle stimulating hormone (FSH) or {Follitropin}-->

gamete production

Luteinizing Hormone (LH or {Lutropin}) -->

gonadal hormones

Gonadotropins are regulated by GnRH, negative feedback, and inhibin

5. Prolactin (PRL)

6. Melanocyte stimulating hormone (MSH) or {Melanotropin}

POSTERIOR PITUITARY storage hormones :

1. Oxytocin

2. Antidiuretic hormone (ADH) or argenine vasopressin (AVP)

Problems seen :
lack of ADH, therefore increased water loss seen with Diabetes Insipidus (DI)
Treatment --> vasopressin as injection or nasal spray.

Excessive ADH: due to neuronal damage or ectopic cancer cells
Treatment--> monitor fluid and Na+ levels

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ENDOCRINE GLANDS

I. Thyroid gland

gross : below larynx, anterior to trachea,  two lobes connected by an isthmus

micro : simple cuboidal epithelial lined follicles that produce colloid that is primarily thyroglobulin

   center cavity (lumen) stores thyroglobulin and iodine trapped by the epithelial cells.

   parafollicular cells....tissue around the follicles produces calcitonin

Two thyroid hormones are produced from tyrosine (-----) on the thyroglobulin and the oxidized form of iodine (*)

tyrosine + 1 iodine --> monoiodotyrosine  (MIT) or T1  *------

tyrosine + 2 iodines --> diiodotyrosine   (DIT) or T2  *------*

Enzymes link  MIT + DIT --> T3 or triiodothyronine   and    DIT + DIT --> T4 or thyroxine                

These thyroid hormones have the same function :

stimulate metabolic rate and tissue growth BUT differ in potency : intensity and duration

T3.......triiodothyronine

T4....thyroxine has a .longer duration, 90% of the thyroid hormone that is produced by the thyroid follicle.

The thyroid gland stores the hormone linked to the thyroglobulin and releases the hormone into circulation.  It can remain free and therefore stay active as thyroid hormones , and then can diffuse into the cell and bind to receptors in the cell  (DNA direct acting system).  The receptors are either in the cytoplasm and the hormone receptor complex then moves into the nucleus or the thyroid receptors can also be found on the mitochondria, thus affecting ATP production.  Because these hormones are considered lipid soluble, they can thereby potentially affect all cells.  Very small amounts of thyroid are in the unbound active state, these are called "free" thyroid hormones. Most of the thyroid hormones are bound to proteins such as albumin, or a specific protien called thyroid binding globulin (TBG). Protein binding of hormones allows for transport to target tissues & then the hormone is released from its protein to have an effect on the cell.

 Controls :                   

          Hypothalamus --> TRH  ==> AP --> TSH ==> Thyroid --> T4, T3

inhibited by glucocorticoids, somatostatin ,negative feedback from T4, T3 concentrations

Thyroid hormone functions :

Thyroid hormone problems :

Thyroid Gland :

Calcitonin from parafollicular cells --> C cells

Control for this Hormone's release is under humoral or blood levels of calcium ion. It is then triggered by high levels of blood calcium.
The final effects are to lower blood calcium levels by effects on skeletal system :

stimulates calcium uptake and storage in bone, target cells are the osteoblasts
inhibits release  primarily useful in children

short duration of effects, overridden by PTH

 

II. Parathyroids

Tiny glands embedded in posterior aspect of thyroid

produce parathormone (PTH) from the chief cells

*** most important control of blood calcium levels.

Calcium is maintained at 9-10 mg % in the blood

If calcium is too low ----Hypocalcemia occurs causes changes in the neuron membrane and makes it more excitable. (decreases in calcium ion cause increases in sodium ion)   neurons fire impulses & cause muscle contraction to the point of tetany affects blood clotting mechanisms

If calcium is too high --- Hypercalcemia (Increases in calcium ion cause decreases in sodium ion) neuronal membranes change, slow down and heart changes seen on ECG  at QT interval
Calcium can precipitate in soft tissues, primarily kidneys.

When calcium levels in the blood fall, PTH stimulates :

1. skeletal system......osteoclasts to digest bone and release calcium, inhibits osteoblasts activity to decrease the rate of calcium deposition.                                                      

2. digestive system....increase absorption of calcium, but Vitamin D is required

3. kidneys...... resorption of calcium and put in back into the plasma via hormonal release of calcitrol (made from Vit D)

Problems :

 

III. Adrenal Glands

Located at superior pole of kidneys; Grossly triangular in shape

structure :

A) Adrenal Cortex......cortical cells arranged in 3 regions

1. Zona glomerulosa

2. Zona Fasciculata

3. Zona Reticularis

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Adrenal Gland Cortical Hormones


Mineralocorticoids :

95% aldosterone

primary regulation of Na+

decreases the secretion of sodium by acting on the distal kidney tubules and collecting ducts to stimulate reabsorption of sodium and allows potassium elimination in the urine. when sodium is reabsorbed, water is reabsorbed by the osmotic gradient that is created.

Aldosterone release controlled by :

a) renin-angiotensin system

in response to decresed Na+, increased K+ renin from the kidneys initiates a cascade that converts angiotensin to angiotensin II to stimulate aldosterone release from the adrenal cortex=s zona glomerulosa.

b) Plasma concentrations of Na+ and K+ can directly affect the zona glomerulosa

c) ACTH  --> increased amounts during stress can cause and increased rate of aldosterone secretion

d) atrial natriuretic peptide (ANP)    old name ANF   (F= factor)

Problems : 

Hypersecretion........Aldosteronism

Hyposecretion ...........Addison's Disease

Glucocorticoids :

synthesized from cholesterol

influence metabolism :  gluconeogenesis by liver (make glucose)  anti-inflammatory, immunosuppressive

allow us to adapt to stress situations  (AP exams :-)

          Three glucocorticoids  (GCC)

Hypothalamus, CRH --> AP, ACTH --> Adrenal Gland, GCC

control by negative feedback due to GCC concentrations

            Problems :

Hyperadrenocorticoidism (Cushings Disease)

Hyposecretion of GCC, usually associated with Addisons disease

Gonadocorticoids from zona reticularis :

Adrenal Medulla Hormones

connections with the sympathetic nervous system since it becomes the postganglionic neuron

hormones secreted :

released in response to sympathetic stimulation. 

Affect tissues with alpha and beta receptors  :

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IV. Pancreas

Endocrine and exocrine gland

associated with the first part of the duodenum of the small intestine

Exocrine pancreas  --> 99% of the pancreass, acinar cells secrete digestive enzymes

Endocrine pancreas --> cluster of cells called the Islets of Langerhans

1) Glucagon

  glucagon will then cause a rise in blood glucose inhibited by somatostatin and high blood glucose

2) Insulin

synthesized as proinsulin

produced by beta cells of the pancreatic islets

effects : lower blood glucose

            enhances membrane uptake & glucose transport into cells

(except for liver, kidney, brain --> no insulin is needed)

glucose is then used for ATP production, or stored as glycogen, or fat

Insulin release is stimulated by :

Problems for Endocrine Pancreas:

hyposecretion or hypoactivity of insulin

causes blood glucose levels to increase --> Hyperglycemia.

  Renal threshold for glucose is reached and glucose is eliminated in urine --> causing glycosuria.

fats are mobilized since glucose cannot be used metabolites form and are called ketone bodies these are acids and will decrease the blood pH levels causing ketosis, also known as diabetic ketoacidosis.

signs : polyuria --> increased urination

therefore :

DIABETES MELLITUS   (DM)  occurs...........

types :  Type I DM, insulin dependent

Type II DM, non insulin dependent

chronic problems of Diabetes ::

               affect the circulatory system.......hemorrhage  because of changes in vascular system

               cataracts...due to change in glucose metabolism in the lens

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V.  Gonads

Female.........ovaries : follicles produce estrogen in response to FSH

            Allow for secondary sex characteristics, and development of reproductive organs, follicular development and oogenesis

Male...........testosterone production in response to LH:

Regulated by GnRH from hypothalamus ==> FSH, LH from AP ==>Gonadotropins

Inhibited by negative feedback of hormone concentrations and inhibin

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VI. Pineal Gland

located in the epithalamus (Aeye brain@) of the diencephalon

produces melatonin

amount of hormone produced is related to visual pathway and light

Melatonin reduces the rate of GnRH,  thereby slowing down reproductive organ activity.

This provides seasonality to lower mammals in regards to reproduction, and stops the heat cycles in winter months to prevent pregnancy and loss of offspring due to decreased survival rates.

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VII. Thymus

located in the anterior mediastinum, behind the upper portion of the sternum

found in infants and children, will atrophy after puberty with the gradual loss of cells and be replaced with adipose tissue

produces hormones essential for development of the immune system. 

The  major hormones are called  : Thymosins. 

            These hormones  have their effects on the lymphocytes to process

            and program them to become Specific Immune System defense cells.

The hormones create and are responsible for producing the group

of lymphocytes known as T-lymphocytes (T-cells) that are necessary for cellular immunity.

Other Tissues with endocrine functions ::

Placenta ::   reproductive hormones

Adipose: Leptin, Resitin, Estrogen

Heart     ::   ANP

Kidneys ::   

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Summary ::

Hormone concentrations are regulated by feedback mechanisms (+/-)

Hormone interactions

Disorders :

Aging :  

Clinical Assessment

Relate results to normal basal levels of hormones using organ function tests

specific tests :

Review Hormone Effects on