Endocrine

Endocrine system function

Acts with nervous system to integrate and control other systems

Endocrine system organ characteristics

Usually epithelial glandular tissue, small and widely scattered, may be ‘true’ organ or part of an organ, and ductless

Endocrine organs

Pineal gland, hypothalamus, pituitary gland, thyroid gland, parathyroid glands, thymus, adrenal glands, pancreas, gonads

Endocrine Signalling Mechanism

Chemical

Endocrine Primary Chemical Signal

Hormones

Endocrine Distance Traveled

Long or short

Endocrine Response Time

Fast or slow

Endocrine Environment Targeted

Internal

Nervous Signalling Mechanisms

Chemical/electrical

Nervous Primary Chemical Signal

Neurotransmitters

Nervous Distance Traveled

Always short

Nervous Response Time

Always fast

Nervous Environment Targeted

Internal and external

Hormones

Steroid based or amino acid based molecules carried via blood to target cells to alter metabolism by changing protein synthesis or enzyme activity

Autocrines

Exert effects on same cells that secrete them, ex. prostaglandins. local chemical messengers that are NOT a part of the endocrine system

Paracrines

exert effects on cells nearby, local chemical messengers and not considered part of the endocrine system

Target cells

Tissues with hormone receptors either on cell membrane or in cytoplasm for a specific hormone. Hormones alter target cell activity.

Amino acid-based hormones

Amino acid derivatives, peptides, and proteins. Mostly water soluble.

Steroids

Built from cholesterol, gonadal and adrenocortical hormones.

Eicosanoids

Not true hormones, includes leukotrienes and prostaglandins

Hormone actions

Opening or closing ion channels, stimulate enzyme or protein synthesis, activate or deactivate enzymes, induce sensory activity, stimulate mitosis

Water-soluble hormones

Includes all amino acid based hormones except thyroid hormone, these hormones act o plasma membrane receptors on the cell surface via G protein second messenger systems. Cannot enter the cell

Two main second-messenger systems

Cyclic AMP and PIP₂- Calcium

Cyclic AMP process

1. Hormone, located in extracellular space, binds to receptor on target

2. Receptor binds to and activates a G protein

3. G protein activates or inhibits effector enzyme adenylate cyclase

4. Adenylate cyclase converts ATP to cAMP

5. cAMP activates protein kinases (enzymes, specifically protein kinase A) that phosphorylate other proteins

6. Phosphorylated proteins are then either activated or inactivated

7. cAMP is rapidly degraded by enzyme phosphodiesterase, stopping cascade

PIP₂-Calcium process

1. Hormone activated G protein activates a different enzyme: phospholipase C

2. Activated phospholipase C splits membrane protein, PIP₂, into two second messengers:

   1. Diacylglycerol (DAG) activates protein kinases

   2. Inositol trisphosphate (IP3) causes calcium release from intracellular storage sites

How does calcium work as another second messenger?

Calcium alters enzyme activity and channels, or binds to regulatory protein calmodulin, which activates enzymes that cause cellular response

Lipid-soluble hormones

Includes steroid and thyroid hormones, enter the cell and act on intracellular receptors and activates genes

Lipid-soluble hormones mechanism of action

1. The steroid hormone diffuses through the plasma membrane and binds to an intracellular receptor and forms the receptor-hormone complex

2. The receptor-hormone complex enters the nucleus

3. The receptor-hormone complex binds to a specific DNA region

4. Binding initiates transcription of the gene to mRNA

5. the mRNA directs protein synthesis

Negative feedback

Reverse changes to maintain balance by producing change in opposite direct, ex: insulin decreasing plasma (glucose). Blood levels of hormones are controlled by negative feedback systems

Positive feedback

Action of the effectors amplifies the changes in the same direction of change, ex: oxytocin during labor, lactation

Hormone release is controlled by which three systems?

Hypothalamus, endocrine gland stimuli, and nervous system modulation

Endocrine glands release hormones in response to which three stimuli?

Humoral stimuli, neural stimuli, and hormonal stimuli

Humoral stimuli

Hormone release caused by altered levels of certain critical ions or nutrients

Neural stimuli

Hormone release caused by neural input

Hormonal stimuli

Hormone release caused by another hormone

Nervous system modulation

The nervous system can modify hormone levels and override endocrine controls

What does the concentration of a circulating hormone reflect?

The rate of release and speed at which it is inactivated and removed from the body

Hormones can be removed from blood by:

Degrading enzymes, kidneys, and the liver

Half-life

Time required for level of hormone in blood level to decrease by half. Varies anywhere from fraction of a minute to a week, depending on hormone. Water soluble hormones are removed quicker than steroid hormones.

How do hormone response times differ?

Some responses are immediate, while others are inactive until they enter target cells. Steroid hormones can takes hours to days.

How do hormone durations differ?

From 10 seconds to hours, dependent on water or lipid soluble

Target cell activation is dependent on which three factors?

Blood levels of hormone, relative number of receptors on/in target cell, affinity (strength) of binding between receptor and hormone

Up-regulation

Target forms more receptors in response to low hormone levels

Down-regulation

Target cells lose receptors in response to high hormone levels; desensitizes the target cells to prevent them from overreacting to persistently high levels of hormone

Antagonism

Hormones that counteract each other; insulin and glucagon

Permissiveness

One hormone requiring another hormone to work, thyroid hormone and epinephrine

Synergism

Multiple hormones produce same effect, causing amplification. Glucagon and epinephrine

Hypothalamus

Neuroendocrine organ responsible for linking the nervous and endocrine systems, producing releasing and inhibiting hormones to control the pituitary gland, and producing oxytocin and antidiuretic hormone

Oxytocin

Hormone responsible for influencing uterine contractions

Antidiuretic hormone (ADH)

Hormone that increases kidney water retention. Can be suppressed by alcohol, which can increase urination while inebriated

Pituitary gland

Gland that maintains homeostasis, reproductive cycles, blood chemistry, and mineral regulation. Divided into two lobes, anterior (adenohypophysis) and posterior (neurohypophysis).

Anterior Pituitary Gland (adenohypophysis)

Part of the pituitary gland composed of glandular epithelial tissue, controlled by hypothalamus. Releases growth hormone, thyroid stimulating hormone, follicle stimulating hormone, luteinizing hormone, adrenocorticotropic hormone, and prolactin.

Growth Hormone

Hormone that promotes cell division of body cells, does not use cAMP or PIP2

Thyroid stimulating hormone (TSH)

Hormone that stimulates thyroid to produce hormones

Follicle stimulating hormone

Hormone responsible for follicle development, estrogen secretion, and sperm maturation

Luteinizing hormone

Hormone responsible for ovulation and testosterone production

Adrenocorticotropic hormone

Hormone that stimulates adrenal glands to produce hormones

Prolactin

Hormone that stimulates milk production in mammary tissue, does not use cAMP or PIP2

Posterior Pituitary Gland (neurohypophysis)

Part of the pituitary gland that is composed of nerve tissue continuous with hypothalamus. Stores and releases oxytocin and ADH made by hypothalamus

Thyroid

Butterfly shaped organ around trachea connected by isthmus that is composed of follicles filled with colloid lined with cuboidal cells. Responsible for the release of thyroid hormone and calcitonin

Thyroid hormone

Consists of two molecules: Thyroxine (T4, the inactive variant) and Triiodothyronine (T3, the active variant). Released by follicular cells, it increases the cell metabolism of all cells but requires iodine to function

Calcitonin

Hormone released by parafollicular cells between follicles, it decreases blood calcium levels and stimulates bone formation.

Steps of thyroid hormone synthesis

• Step 1: TSH activation

• Step 2: Iodide trapping

• Step 3: Oxidation and Iodination

• Step 4: Coupling

• Step 5: Endocytosis and Release

Step 1: TSH activation

TSH binds to receptor inside thyroid follicular cells, which activates cAMP pathway. cAMP activates protein kinases to phosphorylate transcription factors, which play a role in the creation of thyroglobulin, thyroid peroxidase, and Na+/I- symporters.

Thyroglobulin

Molecule that serves as the backbone for the thyroid hormone

Thyroid peroxidase

Enzyme that converts iodide to iodine

Na+/I- Symporters

Passageways that transport iodide into the cell. Requires ATP

Step 2: Iodide trapping

Iodide is actively transported into the follicular cells by symporters, which then transfer iodide into the colloid. For every two sodium ions that enter the colloid across the cell, one iodide can be brought in.

Oxidation

Process by which thyroid peroxidase converts iodide into iodine, which must happen so the ion can be incorporated into the tyrosine residues on the thyroglobulin molecule.

Iodination

Iodine binds to tyrosine residues on thyroglobulin, forming either monoiodotyrosine (MIT) or diiodotyrosine (DIT) based on the amount of iodine and tyrosine molecules.

Step 4: Coupling

The iodinated tyrosines link together to form either T3 or T4. MIT binding to DIT creates T3, DIT binding to DIT creates T4

Step 5: Endocytosis and Release

Iodinated thyroglobulin molecules enter the follicular cells via endocytosis, where they combine with lysosomal vesicles. The lysosomes then cleave T3 and T4 from thyroglobulin and the hormones diffuse directly into the bloodstream.

Parathyroid gland

Four pea-sized glands embedded in the posterior thyroid that release parathyroid hormone

Parathyroid hormone

Hormone that increases blood calcium level by stimulating osteoclasts, also targets the intestines to increase calcium absorption from food and kidneys to activate vitamin D and increase calcium absorption

Adrenal Glands

Pyramid shaped organs on top of the kidneys that regulate stress response, composed of a medulla and a cortex

Adrenal medulla

Inner portion of the adrenal glands made of nervous tissue that is innervated by sympathetic nervous system neurons. Releases epinephrine and norepinephrine in fight-or-flight response.

Adrenal cortex

Outer portion of the adrenal glands made of three layers: Zona glomerulosa (outer), Zona fasciculata (middle), and zona reticularis (inner). Releases more than 25 steroid-based hormones. Release is controlled by the adrenocorticotropic hormone.

Three major types of corticosteroids

Glucocorticoids, Mineralocorticoids, and Gonadocorticoids

Glucocorticoids

Located in zona fasciculata, produces corticosteroids that regulate long term stress and glucose metabolism. Also plays a role in lipid and protein metabolism, and is anti-inflammatory in nature. Ex: Cortisol

Mineralocorticoids

Located in zona glomerulosa, controls electrolytes and water balance in body fluids long term, increases kidney absorption retention of sodium from urine. Ex: Aldosterone

Gonadocorticoids

Located in zona reticularis, produces small amounts of sex hormones

Pancreas

Organ located behind the stomach and over the small intestine that functions both as an exocrine and endocrine organ. Exocrine cells are pancreatic acinar cells which produce enzymes to contribute to chemical digestion, while the endocrine function is controlled by pancreatic islets, which are scattered clusters of alpha and beta cells.

Alpha cells

Cells that make glucagon, which increases blood glucose levels by targeting the liver to release stored glucose

Beta cells

Cells that make insulin, which reduces blood glucose level by increasing uptake by cells. Targets mainly skeletal muscle, liver, and adipose cells

Pineal gland

Located on posterior aspect of diencephalon, secretes melatonin

Melatonin

Hormone that regulates sleep wake cycles and circadian rhythms

Thymus

Controls immune system cell development in children, degrades in adults

Testes/ovaries

Produces sex hormones. Ovaries produce estrogens and progesterone in females, testes produce testosterone in males.

Stomach and small intestine endocrine function

Secretes hormones controlling digestion

Heart endocrine function

Secretes hormones that decrease blood volume

Kidneys endocrine function

Secretes hormones that increase calcium and phosphate absorption and RBC production