ENDO EXAM 1

What is endocrinology

The study of hormones, their receptors, and the intracellular signaling pathways and responses.

Endocrine

hormones released into the blood stream

Paracrine

hormones that act on nearby cells

Autocrine

hormones that act one the same cell that secreted them

Neuroendocrine

neurons that release hormones into the blood

Examples of endocrine tissues

hypothalamus

pituitary gland

thyroid gland

parathyroid gland

thymus

pineal gland

adrenal glands

pancreas

kidneys

testes

ovaries

Examples of endocrine hormones

insulin, cortisol, T3/T4, estrogen, testosterone, growth hormone

What was the design and outcome of Berthold’s 1849 experiment?

This was the first scientific study of behavioral endocrinology. The castrated roosters showed no male characteristics unless testes were reimplanted. The testosterone produced by the testes was responsible for the chicken’s development into an adult rooster.

What is compensatory hypertrophy?

increase in size of an organ to compensate functionally for loss of other organ

How was it shown that a factor made from the pancreas could regulate carbohydrate metabolism?

Removing the pancreas caused diabetes in dogs. Extracts from the pancreas reversed this, leading to the discovery of insulin.

What is homeostasis?

maintaining stable internal conditions

Why is homeostasis important?

keeps the cells functioning properly; an imbalance leads to disease.

What is physiological temperature and pH?

temp: 98.6

pH: 7.35-7.45

Why is it important to maintain blood glucose concentrations?

brain and muscles rely on glucose. imbalance= hypoglycemia and diabetes

Why is it important to maintain blood calcium concentrations?

essential for muscle contraction, neurotransmission, and clotting.

What other physiological parameters are controlled by endocrine hormones?

blood pressure

growth

metabolism

stress response

reproduction

immune regulation

What types of proteins are needed to mediate hormone action and where are they located within the cell?

receptors, g proteins, kinases, phosphatases.

receptors are in the membrane, nucleus, and cytoplasm.

Distinguish between humoral, somatic, and neural.

Humoral: bodily fluids

Somatic: body-wide physical responses

Neural: stimulated by nerves

What types of “other cells” make up tissues?

hormone-producing cells, support cells, immune cells, and blood vessels

Distinguish between endocrine and exocrine.

Endocrine: secretes hormones into blood

Exocrine: uses ducts to secrete onto surfaces

Usually, one cell type in a tissue or organ will be responsible for hormone production. List an example.

beta cells in pancreas make insulin

What is a transient endocrine gland? What is an example?

an organ that produces hormones only for a short period of time before it degenerates and is replaced by another gland. ex: placenta

Some tissues only make hormones at certain times during lifetime. Give an example for humans.

thymus (active in childhood)

Do endocrine tissues usually produce more than one hormone? Are there any exceptions?

yes, the pancreas makes insulin and glucagon.

the parathyroid and pineal are the only exceptions because they produce one hormone.

What was the first hormone defined and what is its function?

secretin (stimulates flow of pancreatic juice)

What is the developmental origin of all types of hormones?

ectoderm, mesoderm, and endoderm

Can a hormone be made in more than one location?

yes, hormones can be produced at different sites for different functions.

What covalent modification is common for most peptide hormones? Why is this important?

glycosylation. affects stability and function.

What are the four types of non-covalent interactions? How are they important in hormone structure and action?

hydrogen bonds, ionic bonds, van der waals, and hydrophobic interactions.

they stabilize hormone-receptor binding.

What is the secretory pathway?

Hormones are synthesized, modified, sorted, and secreted from endocrine cells to target cells.

What organelles are involved in the secretory pathway?

ER → Golgi → vesicles → membrane.

Distinguish between two populations of secretory vesicles (continuous and regulated).

Continuous: constant release

Regulated: stimulus-triggered

Do hormones have the same function and sequence in every species?

varies depending on the type of hormone

Name an endocrine hormone that is highly conserved across species.

Insulin

What are the two thyroid hormones, their general functions, and one unique property?

T3 and T4. Increase metabolism. They need Iodine.

Where are steroid hormones produced? What are the five general types?

made in the adrenal cortex and gonads.

types: androgens, estrogens, progestins, glucocorticoids, mineralocorticoids

How does the solubility of peptide and steroid hormones contribute to their mode of action?

peptide: water soluble → act on surface receptors

steroid: lipid soluble → cross membranes → intracellular receptors

What is a neurotransmitter? Give an example.

chemical messenger to transmit signals to another neuron, muscle cell, or. gland

example: dopamine

Give some examples of peptide growth factors and their very general functions.

EGF, NGF → regulate growth

What are eicosanoids?

a large group of lipid-based signaling molecules derived from 20-carbon polyunsaturated fatty acids (PUFAs)

What are some of the different types of eicosanoids?

Prostaglandins, prostacyclins, leukotrienes and thromboxanes

How are prostaglandins named?

named by letter + number

What are prostaglandins made from? Where were they first discovered?

Made from fatty acid substrates (AA) within membranes of cells.

First discovered in seminal fluid.

Pheromone

chemicals affecting other organisms behavior

How can pheromones be dispersed?

in the air or an aquatic environment

What was the first pheromone, its function and how was it purified.

Bombykol (moth sex attractant). Purified by removing certain glands at the tip of the abdomen.

What is evidence that pheromones exist in humans?

groups of women who live together tend to get their period the same time of the month.

What hormone is a human pheromone?

androstadienone

Has a human pheromone been purified?

no

What are some non-traditional cellular messengers that can act as hormones? Give some examples.

nitric oxide (NO), carbon monoxide (CO), retinoic acid

What amino acid is needed for production of thyroid hormones?

tyrosine

Tryptophan is needed for production of what hormones?

Serotonin and melatonin

What amino acid is needed for histamine production?

Histidine

Where are peptide hormones produced within cells?

made in rough ER → golgi → secretory vesicles

Where are steroid hormones made in the cell and how can these cells often be recognized?

made in smooth ER and mitochondria. recognized by lipid droplets.

What are prohormones and preprohormones? Give some examples.

inactive protein precursors that are modified to produce the final active peptide hormone. (preprohormone → prohormone → active hormone)

ex: proinsulin → insulin

How does this regulation of prohormones impact hormone action?

controls the timing and location of hormone action

Hormones often function to induce secretion of other hormones. Give some examples of these cascade effects.

TRH → TSH → T3/T4 → CRH → ACTH → CORTISOL

Why do peptide hormones have short lives and steroid hormones have long lives?

Peptide: short lives due to enzymes in blood

Steroids: long lives due to binding proteins

Define endopeptidase and exopeptidase.

Endopeptidse cleaves inside chain. Exopeptidase cleaves from ends.

What physiological processes do hormones regulate? 

metabolism, cell growth and development, reproduction, homeostasis

Besides receptors, what proteins or mediators are involved in hormone action?

second messengers, kinases, and phosphatases

What two types of hormones have intracellular receptors?

Steroid and thyroid

Do specific hormones affect all cells in an organism? Why or why not?

not all cells respond, only if they have the receptor

Where are hormone receptors located in the cell? 

membrane, cytoplasm, and nucleus

Give some specific examples of how hormone levels or receptor levels modulate hormone action.

the concentration of a hormone in the bloodstream directly affects the magnitude of the cellular response

What % of receptors needs to be occupied for a maximal cellular response? WHY?

5-10% of receptors occupied can trigger a full response

What are 3 characteristics of G protein coupled receptors (GPCR)?

7 transmembrane domains, G protein activation, second messenger signaling

What is a trimeric G protein? How is it activated?

alpha, beta, gamma subunits. activated when hormone binds to GPCR

What are some second messengers activated by these proteins?

cAMP, IP3, DAG, Ca2+

What types of physiological responses are due to 7TMD receptors?

they detect extracellular stimuli and trigger intracellular signaling pathways

What is a kinase?

an enzyme that adds a phosphate group

What is phosphatase?

an enzyme that removes a phosphate

What amino acid residues are substrates for these enzymes?

serine, threonine, tyrosine

How is adenylate cyclase activated? What kinase does it induce? How does this effect transcription?

activated by Gas, which converts ATP to cAMP. cAMP activates PKA → phosphorylates CREB → changes transcription

What are the 4 different types of cell surface receptors and give an example of each.

1. GPCRs - glucagon

2. Tyrosine kinase - insulin

3. Cytokine receptors (JAK/STAT) - GH

4. Intracellular - cortisol

What is CREB?

transcription factor for cAMP response

What is the JAK STAT pathway?

a signal pathway that transmit information from the cell surface to the nucleus, leading to gene expression. bypasses second messengers.

What hormones utilize this pathway? (JAK/STAT)

cytokines (GH, prolactin, and leptin)

What 2 phosphorylation events is the JAK responsible for?

phosphorylation of the receptor and the STAT proteins

What are the steps involved in STAT activation?

STAT dimerizes and translocates to the nucleus to bind to DNA and regulate gene transcription

Define adenylate cyclase.

an enzyme that converts ATP to cAMP

How does cAMP result in the activation of PKA?

by binding to its two regulatory subunits, causing a conformational change that releases the two inactive catalytic subunits

What kind of enzyme is PKA?

serine/theronine kinase

What transcription factor (TF) is phosphorylated by PKA? Where does that TF bind?

CREB. CREB binds to a specific DNA sequence called CRE (cyclic AMP response element)

What happens as soon as a hormone response is induced?

the hormone binds to a specific receptor on or inside the target cell

Are cAMP and cGMP labile? What is a PDE and how does it affect these second messengers

yes, they are labile because they are actively degraded by enzymes call PDEs.

PDEs= phosphodiesterases

PDEs inactivate second messengers

What are methxanthines and how do they effect cAMP levels?

naturally occurring compounds found in food and beverages (ex: caffeine) . they inhibit PDE which increases cAMP levels.

Do all G proteins activate cAMP?

no, they either stimulate or inhibit it.

Do all G proteins utilize second messengers? Explain

no, some activated G proteins directly open ion channels, which allows ions like calcium to act as second messengers.

What is arachadonic acid, IP3, DAG, PKC and PLC?

arachidonic acid → makes prostaglandins

IP3 → releases calcium from ER

DAG → activates PKC

PLC → located in the cell membranes and activated by G-proteins

Where is calcium stored in the cell?

ER

What are the different types of eicosanoids? Where in the cell are they made? How do they act?

prostaglandins, thromboxanes, leukotrienes, and prostacyclins.

made in the membrane; act locally

Are they short or long lived? (eicosanoids)

short lived

What are prostacylins and what is their primary function?

vasodilation, inhibit clotting

What two prostaglandins affect blood flow in opposite ways?

prostacyclin and thromboxane (this opposing relationship is key to regulating blood vessel tone and blood clotting)

What hormones have intracellular receptors? How are these hormones activated?

steroid and thyroid hormones. they activate their receptors by diffusing across the cell membrane.

What is an ERE, a TRE, a GRE, an ARE. Where are they found?

EREs: estrogen response elements

TREs: thyroid hormone response elements

GREs: glucocorticoid response elements

AREs: androgen response elements

found in promoters of target genes.

What is hypertrophic and atrophic?

hypertrophic is bigger cells and atrophic is a decrease in size

What is hyperplasia?

an increase in the number of cells