PSIO 241 CH 17

endocrine system

• Consists of **ductless endocrine glands** scattered throughout body

• Glands secrete hormones which **travel through blood** to target cells

– Target cells have receptors for binding with specific hormone

– Regulates or directs specific functions

**Hydrophilic-water soluble hormones**

• Peptide hormones

• Catecholamines (NE)

**Lipophilic-lipid soluble hormones**

• Steroid hormones

• Thyroid hormone 

tropic hormones

• **Regulates hormone secretion by another endocrine gland**

• Stimulates and maintains their endocrine target tissues and system provides **negative feedback**

endocrine dysfunction

• Can arise from a variety of factors

• Most commonly result from abnormal plasma concentrations of a hormone caused by inappropriate rates of secretion

hypo secretion

too little hormone is secreted

hypersecretion

too much hormone is secreted

primary disease

occur when the actual gland is not working correctly

secondary disease

occurs when another structure is not working correctly and affects gland function

hormones

• bring about cell responses primarily  by signal transduction

– process by which incoming signals are conveyed to target cell’s interior

first messenger

• Binding of hormones **(first messenger)** to matching receptor brings about intracellular response by either:

– Opening or closing channels

– **Activating second-messenger systems** which relays message to intracellular proteins that carry out specific response

second messenger

Some hormones **do not utilize second messenger systems** and directly enter the cell to bind with their receptor and affect protein synthesis

pituitary gland

• Small gland located in bony cavity just below hypothalamus

– Thin stalk connects pituitary gland to hypothalamus

• Consists of two anatomically and functionally distinct lobes:

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**Posterior pituitary (neurohypophysis)**

• Composed of nervous tissue

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**Anterior pituitary (adenohypophysis)**

• Consists of glandular epithelial tissue

hypothalamus and posterior pituitary

1. The paraventricular and supraoptic nuclei contain neurons that produce **vasopressin (ADH) and oxytocin.**  
2. The hormone is **synthesized in the neuronal cell body in the hypothalamus.**
3. The hormone travels down the axon to be **stored in the neuronal terminals** within the posterior pituitary.
4. On excitation of the neuron, the **stored hormone is released** from these terminals in the **posterior pituitary** into the systemic blood for distribution throughout the body.

anterior pituitary hormones

1. Thyroid-stimulating hormone (TSH)
2. **Adrenocorticotropic hormone (ACTH)**
3. Follicle-stimulating hormone (FSH)
4. **Luteinizing hormone (LH)**
5. Growth hormone (GH)
6. Prolactin (PRL)

Thyroid-stimulating hormone (TSH)

stimulates secretion of thyroid hormone

Adrenocorticotropic hormone (ACTH)

stimulates secretion of cortisol by adrenal cortex

**Follicle-stimulating hormone (FSH**)

in females, stimulates growth and development of ovarian follicles; promotes secretion of estrogen by ovaries; males required for sperm production

Luteinizing hormone (LH)

in females, responsible for ovulation and luteinization; regulates ovarian secretion of female sex hormones; males, stimulates testosterone secretion

**Growth hormone (GH)**

primary hormone responsible for regulating overall body growth; important in intermediary metabolism

Prolactin (PRL)

non-tropic hormone; enhances breast development and milk production in females

GHRH

major controller of GH. Its release stimulated by **sleep, low blood glucose, exercise**

growth hormone direct actions

• **Increases fatty acid levels** in blood by enhancing breakdown of triglyceride fat stored in adipose tissue

• **Increases blood glucose levels** by decreasing glucose uptake by muscles; growing muscle/bones uses fats as energy source; allows glucose to be saved for brain called __**glucose sparing**__

• GH controls growth of tissue by increasing amino acid uptake

growth hormone indirect actions

•promotes growth by stimulating liver’s production of **growth factors.** Primary growth factor is **insulin-like growth factor-1 (IGF-1).**

insulin-like growth factor-1 direct actions (IGF-1)

• acts directly on bone and soft tissues to bring about growth

• stimulates protein synthesis, cell division, lengthening/thickening of **bones**

• affects muscle growth

• **has much longer half life than GH**

growth hormone excess

• Most often caused by tumor of GH-producing cells of anterior pituitary

• Symptoms depend on age of individual when abnormal secretion begins

gigantism

overproduction of GH in childhood before bone growth plates close

acromegaly

– overproduction of GH after bone growth plates close; abnormal growth of bone of hands and face; soft tissues; heart; elevated glucose 

– Best marker for this condition **is IGF levels** not GH levels

follicle

Functional unit of the thyroid gland 

lumen

filled with **thyroglobulin**, contains large numbers of thyroid hormone molecules

follicle cells

function to synthesize, and release thyroid hormones

thyroid gland

• Dietary intake of about 500 μg per day is typical, mainly in the form of iodide (I–) or iodine (I).

• Produces two **iodine-containing** hormones derived from amino acid tyrosine:

• Tetraiodothyronine (T4 or thyroxine)

• Tri-iodothyronine (T3)

TSH

synthesis and secretion driven by _

TH storage

Usually, enough thyroid hormone stored to supply body’s needs for several months

TH (thyroid hormone) secretion

– Gland releases T4 and T3 into blood (20:1) and due to many factors, the ratio in circulating plasma can be as high as 50:1

– T3 has more biological activity

– Tissues can covert T4 into T3

regulation of secretion of TH

• Regulated by **negative-feedback system** between hypothalamic TRH, anterior pituitary TSH, and **T4**

• Feedback loop maintains thyroid hormones at **relatively constant levels**

hashimoto thyroiditis

an **autoimmune disease** that destroys thyroid cells by cell an antibody-mediated immune processes. The pathology of the disease involves the formation of antithyroid antibodies that attack the thyroid tissue, causing progressive fibrosis. **It is the most common cause of hypothyroidism in developed countries.** 

causes of hypothyroidism

• **Loss of TSH from anterior pituitary**

• **Severe iodine deficiency**

• Failure to escape from **Wolff-Chaikoff** effect following excessive iodine uptake

hypothyroidism symptoms

due to lower metabolic activity

↓ BMR-Less energy expenditure at rest

Poor tolerance to cold- lack of calorigenic effect

Excessive weight gain-reduced intracellular fuel consumption

Easily fatigued-reduced energy production

Slow, weak pulse- ↓ HR, ↓ contractility à ↓ CO

Slow reflexes and metal responsiveness-due to reduced effects on nervous system

Edema-carbohydrate infiltration in skin **(myxedema);** can occur in severe hypothyroidism, especially in patients older than 60-years-old

**Treatment-hormone replacement therap**

cretinism

• Untreated postnatal hypothyroidism; infants can have normal appearance following delivery, but may display, respiratory difficulty, jaundice, feeding problems, hypotonia

• **Hypothyroidism causes rapid, irreversible abnormalities in nervous system maturation**

Patients also exhibit **abnormalities of bone and muscle development**

Grave’s disease

• Autoimmune disease; body produces thyroid-stimulating immunoglobulins (TSI)

• These **bind TSH receptors** on the thyroid and **promote hormone synthesis and release**

• Laboratory tests would show **↑ FT4, ↓ TSH**

• Characterized by exophthalmos (eye protrusion); **thyroid eye disorder**

• Accelerated metabolism, weight loss, agitation, increased blood pressure, tachycardia

adrenal glands

• Embedded above each kidney 

• Composed of two endocrine organs:

adrenal cortex-outer portion

adrenal medulla

adrenal cortex-outer portion

secretes steroid hormones

adrenal medulla

inner portion, secretes catecholamines NE and E in times of **sympathetic stress response**

zona glomerulosa

• makes mineralocorticoids

– **Mainly aldosterone;** influences Na+ and K+ balance

zona fasciculata

•makes glucocorticoids

–**Mainly cortisol**

–Major role in glucose metabolism as well as in protein and lipid metabolism and helps body deal with **chronic stress**

zona reticularis

•makes male sex-hormones (androgens)

–Does not produce testosterone, but produces **intermediary androgens** that can be converted to testosterone in tissues

–Most abundant and physiologically important **isdehydroepiandosterone (DHEA) and androstenedione**

Not important in adult males

mineral corticoids

Major hormone is **Aldosterone:**

•Primary action on Principal cells of nephron, cells reabsorb Na+, ECF volume increases; cells secrete K+ and H+

•Secretion is increased by renin-angiotensin-aldosterone system and hyperkalemia

•Regulation of aldosterone secretion is **largely independent of anterior pituitary control**

glucocorticoids

Major Hormone is **Cortisol:**

•Raises blood glucose levels by breaking down proteins and increases fat metabolism

•Plays key role in **adaptation to chronic stress**

•At pharmacological levels, can have **anti-inflammatory and immunosuppressive effects**

•Displays a characteristic **diurnal rhythm**

•Secretion regulated by negative-feedback loop involving **hypothalamic CRH and pituitary ACTH**

cortisol and metabolism

• __Protein__

–Cortisol promotes degradation of **proteins into amino acids**

–Amino acids used by liver to make new glucose **gluconeogenesis**

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• __Lipids__

–Cortisol promotes lipolysis and increased delivery of **free fatty acids and glycerol (to make new glucose)**

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• __Carbohydrates,__ cortisol **raises** blood glucose

1\.Increases hepatic output of glucose via **gluconeogenesis**

2\.Counteracts insulin’s action in most tissues, **ensures glucose is not taken up by cells unnecessarily during stress, saves glucose for brain**