MBS 603 Final Exam set

Functions of the endocrine system

1. maintain steady-state

Where does the endocrine system begin?

Hypothalamus and Pituitary

Hypothalamus Role in nervous system

Sensor for changes in the environment externally and internally then regulates autonomic functions response such as temperature, hunger, and sleep, and controlling the pituitary gland.

Where is the hypothalamus located?

Centrally located at the base of the brain

Pituitary Stalk

Connector between the hypothalamus and pituitary gland.

What is important to remember about the anterior and posterior pituitary glands?

They are derived embryologically from different sites.

How are anterior and posterior pituitary gland

During brain development, an extension forms the posterior pituitary, while the anterior pituitary develops from an outpouching of the oral cavity. ,

Is the posterior pituitary a part of the brain?

Yes, it is made from neural tissue and responds to stimuli

Is the anterior pituitary part of the brain?

No, it is derived from epithelial tissue and not part of the central nervous system.

What type of response is given after the hypothalamus and pituitary communicate?

an endocrine response

Endocrine

a hormone or a substance created at one site travels through the blood stream to high affinity receptors at a distant site. (Travel)

Paracrine

Where a substance is produced in one cell, leaves the cell, and affects nearby cells. (Neighboring)

Autocrine

Where is a substance is produced, leaves the cell, and acts upon the cell it just left. (Self)

Neuroendocrine

A substance produced by the central nervous system travels to distant high affinity receptors.

Neuroendocrine hormones

releasing hormones that come from the hypothalamus

Is the pituitary a part of the brain?

No, due to the development

Types of hormones

1. Peptide and and protein

2. Amine

3. Steroid

Examples of peptide and protein hormones

Growth Hormone

ACTH

Insulin

Glucagon

Peptide and protein hormone synthesis

gene for hormone in nucleus transcribed → mRNA → mRNA translated on ribosome in the cytoplasm → perprohormone with signal peptide → signal peptide removed via endoplasmic reticulum and converted to a prohormone → prohormone transferred to the Golgi and package into secretory vesicles → proteolytic enzymes in the vesicles cleave prohormone to be active

What is the benefit to having storage available for the endocrine system

enables immediate action when stimulated

What is the largest distinction between the peptide and protein hormones and the other 2 types?

Hormones are able to be stored in secretory vessels enabling immediate response to stimuli

Protein and Peptide hormone storage

the active form of this hormone is stored in secretory vesicles of the Golgi Apparatus

Protein and peptide hormone release

An endocrine cell, upon stimulation by a signal that activates a G-protein-coupled receptor (GPCR), initiates a signaling cascade that increases intracellular cAMP via adenylyl cyclase. The elevated cAMP activates protein kinase A (PKA), which can enhance intracellular Ca²⁺ levels—either by promoting calcium influx or release from intracellular stores. The rise in intracellular Ca²⁺ then triggers exocytosis, leading to the release of hormones into the bloodstream.

What molecular event indicates that there will be an endocrine response?

A rise in Ca2+ concentration

Example of Amine hormones

1. Catecholamines

2. Thyroid Hormones

Amine hormone synthesis

Derived from Tyrosine

Amine hormones storage

No storage and must be made upon signaling

Examples of Steroid hormones

1. Cortisol

2. Testosterone

What is the most important molecular factor in the reproductive system?

Cholesterol

What would happen without cholesterol?

1. No cortisol

2. No reproductive system

3. Homeostasis cannot be maintained

What happens when there is no cortisol?

Stress can not be signaled to maintain steady-state

Where are steroid hormones synthesized?

cytoplasm and mitochondria

Steroid hormone synthesis

Cholesterol from diet (chylomicrons) enters liver → Acetyl CoA acts on chylomicrons to convert to VLDL → VLDL secreted from liver into blood → VLDL travels as LDL through the bloodstream → LDL is phagocytosed into cell and then into Lysosome → LDL is broken down into amino acids, cholesterol, and fatty acids → 20% of LDL broken down into acetyl CoA & 80% LDL to cholesterol → Actelyl CoA + Cholesterol in cell make pregnenolone → pregnenolone broken down to Aldosterone, Cortisol, Testosterone, and Estradiol

 

What is the rate limiting step for steroid synthesis?

The initial step where cholesterol is converted to pregnenolone catalyzed by cholesterol desmolase.

What happens to peptide and protein hormones when they enter the blood stream?

They must bind to a high affinity receptor

GPCR differences

the alpha chain used by the receptor

Gs

Stimulatory GCRP

G alpha-i

inhibitory GCPR

G alpha-q

stimulatory GCPR

Which GCPR cause a rise in intracellular Ca2+ concentration

Gs and G alpha-q

What makes secretory vessles move towards the cell membrane for release?

rise in intracellular Ca2+

What happens during Gs stimulation?

Adenyl cyclase is activated and increases production of cAMP and PKA is stimulated

Increased cAMP production

Opens c alcium channles on the surface of the cell causing influx of calcium into the cell

What happens when G alpha-q is stimulated?

Intracellular stores of Ca2+ are released from the endoplasmic reticulum which means an increase in secretion. PKC is stimulated

What happens when Gi is stimulated

Ca2+ secretion is inhibited

Insulin receptor structure

heterodimer with 2 in ECF and 2 in ICF

Insulin receptor ICF domain

Has enzymatic activity (like kinase ) because it is phosphorylated during stimulation

How does the growth hormone receptor differ from the insulin receptor?

It has phsphorylating activity domains that associate with it and is not part of the receptor itself

What is the main source of cholesterol?

Food that is processed in the liver to LDL

What type of receptor is needed for steroid hormones to act?

intracellular hormone receptor

Steroid hormone release

Lipophilic nature allows for steroid hormones to enter ICF via passive diffusion → steroids bind to cytosolic receptors or nuclear receptors → once bound, the receptor dimerizes and binds to steroid-responsive elements to act as a transcription factor → This stimulates or represses the transcription of a gene

What happens when cortisol levels stay high?

1. Tachycardia (increased heart rate)

2. Hypertension (raised BP)

3. Shut down reproductive function

Negative Feedback

the internal regulatory system that make sure hormones levels are not too high in the body

Endocrine axis negative feedback (classic mechanism)

1. Hypothalamus releases a releasing hormone (neuroendocrine)

2. Neuroendocrine hormone acts on the pituitary gland, producing a tropic hormone

3. Tropic hormone binds to a peripheral gland

4. hormones produced peripherally travel back to the pituitary adn hypothalum to turn off releasing and tropic hormones

Tropic actions

causing a positie stimulus to where ever a tropic hormone binds

Physiologic response driven feedback (non-classic mechanism)

1. Physiologic response (low blood sugar)

2. peripheral organ begins to correct using hormone(pancreas releases glucagon)

3. physiologial change turns off the activity of the hormone (blood sugar rising back to normal)

Examples of physiologic response driven feedback

1. Insulin-Glucagon system

2. Calcium regulatory system

How does the hypothalamus communicate to the anterior pituitary?

1. The hypothalamus has axons that extend to the pituitary stalk

2. Releasing hormones are released in the pituitary stalk and enter the hypothalamic-hypophyseal portal system

3. Once entered into the anterior pituitary the RH look for cytophils with the correct receptors

Hypothalamic-hypophyseal portal system

Intricate circulation that picks up RH and delivers them to the anterior pituitary

Median eminence

The region of the pituitary stalk where RH to enter the hypothalamic-hypophyseal portal system

Tropes

Cells that produce pituitary hormones

Lactotropes

produce prolactin (PRL) for breast development and breast milk production

Thyrotropes

Produce thyroid stimulating hormone (TSH)

Gonadatropes

Produce LH and FSH that stimulate the gonads

Corticaltropes

Produce ACTH which stimulates the adrenal cortex to produce cortisol

Somaditropes

produce growth hormones responsible for the regulation of linear growth and glucose level

5 characteristics of releasing hormones

1. Secreted in pulses

2. bind to specific plasma membrane receptors

3. secondary messenger systems in target cells (calcium, cAMP, PKC)

4. Stimulate the release of stored target anterior pituitary hormones via exocytosis

5. Stimulate synthesis of target anterior pituitary hormones

What anterior pituitary hormone is being tonically suppressed?

Prolactin (PRL)

How is PRL tonically suppressed?

Dopamine

Why are RH secreted in pulses throughout the day?

Always assures there are fresh receptors on the surface of pituitary cells

Suprachiasmatic nucleus

regulates that carcadian rhythm in the hypothalamus

Primary Endocrine disease

there is a disfunction in the peripheral gland

Secondary Endocrine disease

There is a disfunction in the pituitary gland

Tertiary Endocrine disease

There is a disfunction in the hypothalamus

Long-loop feedback

When a hormone secreted by a peripheral endocrine gland (e.g., cortisol from the adrenal cortex) feeds back to inhibit the hypothalamus and/or pituitary.

Short-loop feedback

When a tropic hormone from the pituitary feeds back to inhibit hypothalamic hormone secretion.

How does the hypothalamus communicate with the posterior pituitary?

1. The hypothalamus has axons that extend to the posterior pituitary

2. The hormones are produced in the axon and travel into the blood stream surrounding the posterior for circulation

What hormones are produced in the posterior pituitary?

None

Posterior pituitary hormones

1. ADH (vasopressin in the kidneys)

2. Oxytocin (Mammary glands and uterus)