Endocrine Principles

The entire umbrella of the endocrine network consists of (other systems):

1. endocrine glands 2. the CNS and PNS (the nervous system) 3. the immune system Organs belonging to these systems secrete endocrine hormones

Hormone secreted by the stomach to know: list name, type of hormone, and its major functions

Gastrin is a peptide hormone, responsible for stimulating the secretion of HCl by parietal cells in the stomach mucosa. MAKES THINGS MORE ACIDIC.

Hormones interact with: Hormones are released from:

Hormones interact with receptors on target cells Hormones are released from endocrine glands, the heart, the liver, the brain and fat!

Target organs must express:

Target organs must express hormone receptors They then alter their function based on hormones binding to their receptors

Protein/Peptide hormones vs steroid hormones: Which are water soluble? Which require a carrier protein in plasma? Which are stored in vesicles? Where is the receptor location at the target cell? Mechanism of action? Speed and duration

see photo *note: the amine class has variable characteristics - the catecholamines (NE, epi, dopamine) behave like peptides, but the thyroid hormones behave like steroids.

Hormone *intracellular receptors* involve:

- the hormone crossing the cell membrane by diffusion (if lipid soluble) or transport and binding to the receptor intracellularly - the hormone-receptor complex may then bind to specific consensus sequences on the DNA to directly activate or repress gene expression! (ex; think estrogen dependent gene expression!) *generally seen with steroid hormones and thyroid (amine) hormones!

Hormones secreted by the hypothalamus

-The releasing hormones: Thyrotropin-releasing hormone (TRH), Corticotropin-releasing hormone (CRH) and Gonadotropin-releasing hormone (GnRH) *Hypothalamus releases--->Anterior Pituitary Releases from stimulation of Hypothalamus ---> target organ: Gonadotropin-releasing hormone (GnRH) ------> FSH & LH ---> ovaries and testes (estrogen, progesterone, testosterone) Thyroid-releasing hormone (TRH) ----------------> TSH -----> Thyroid Corticotropin releasing factor (CRH) --------------> ACTH* ----> adrenal cortex of kidney (cortisol, aldosterone, androgens) -Inhibitory hormones: somatostatin, dopamine, vasopressin, oxytocin

What are potential issues that may arise with hormone receptors? How are receptors regulated?

-hormone levels are off (too low or too high) -number of receptors is off (too low or too high) -receptor loses its affinity/becomes desensitized to the hormone (as in diabetes) Receptors can be upregulated (increase in number) when hormone level is low! Receptors can be downregulated or desensitized when hormone level is high or TOO CONTINUOUS. Receptors can be internalized via endocytosis.

Hormone Transport

-hormones can circulate either free or bound to proteins/in vesicles -only free/unbound hormones are active!! -metabolic clearance of hormones depends on the *volume* of plasma containing the hormone clearer per unit time >metabolic clearance will depend on receptor internalization, carrier proteins, and elimination

Hormone Carrier Proteins - what is their role? what effect do they have? where are many of them made? are they specific or nonspecific?

-protein binding can increase the hormones *half life and delay onset of action* -many carrier proteins are made in the liver (so liver function can drastically affect your hormone function) -some carrier proteins are specific (sex hormone binding proteins) while some are nonspecific (albumin)

Two classes of hormone receptors

1. Cell membrane (protein hormones! Amine catecholamines!) --> includes GPCRs, Receptor tyrosine kinase, and ion channels 2. Intracellular (steroid hormones! Amine thyroid hormones!)

Two hormones secreted by the small intestine to know: list name, type of hormone, and its major functions

1. Cholecystokinin (CCK) is a peptide hormone, responsible for stimulating release of pancreatic enzymes, contracting the gallbladder, relaxing the sphincter of Oddi, inhibiting stomach motility, TELLING YOU WHEN YOU ARE FULL. 2. Secretin is a peptide hormone, responsible for increasing fluid and bicarbonate secretion by the pancreatic duct, feedback inhibition of gastric HCl/H+ secretion. MAKES THINGS MORE BASIC

**important: Which hormones are key in maintaining homeostasis? (3 we focused on)

1. Cortisol 2. Mineralcorticoids (ALDOSTERONE) 3. Insulin

Hormone *cell membrane receptors* use signal transduction pathways (which are nonlinear in real life); these may involve:

1. GPCRs: receptors couples to a protein that binds GTP and is also linked to an enzyme which has some other action in the cell. 2. Receptor tyrosine kinases: generally phosphorylation mediated 3. Ligand gated ion channels *generally seen with peptide hormones!

Functions of the endocrine system

1. Maintain homeostasis 2. Coordinate activity in the body 3. Produce effects in distant organs via hormones

5 Modes of Intracellular communication1

1. Neural - rapid information transfer using electrical signals; release of NT between neuron and target cell 2. Endocrine - release of chemical transmitter (hormone) by specialized cells to target via blood 3. Neuroendocrine - release of "neurohormone" by neuroendocrine cells (such as those in the hypothalamus or anterior pituitary) into the blood 4. Paracrine - cells secrete chemical transmitters locally - target their neighbors with hormone via diffusion 5. Autocrine - cells regulate themselves via release of hormone/chemical messenger

Three classes of Hormones

1. Proteins/Peptides - the largest group, *post-translationally processed* from zymogens to the active form, released by *exocytosis* from secretory granules, bind to PM receptors so don't make it into the cell 2. Steroids - *derived from cholesterol,* made by the adrenal cortex, testes/ovaries, placenta, *lipid soluble* so must travel bound to proteins, bind to *intracellular receptors - cytosolic or nuclear* 3. Amines - *derived from tyrosine,* include epi, NE, dopamine, thyroid hormones

List Hormone; Source (gland); Action for: Cortisol Mineralcorticoids Insulin **know!

All three are very important for homeostasis! 1. Cortisol is made by the adrenal cortex, and its action is to assist in *energy metabolism*; it is also *permissive* of other hormones (its presence is needed for other hormones to be secreted) 2. Mineralcorticoids are also made by the adrenal cortex, and they regulate *plasma volume* via effects on serum *electrolytes* --> *ALDOSTERONE IS THE MAIN MINERALCORTICOID* 3. Insulin is made by the pancreas (beta cells), its role is to regulate plasma/blood glucose concentration

Hormones secreted by the adrenal glands - both cortex and medulla (think acronym)

CANE-A -Cortisol, aldosterone, norepinephrine, epinephrine, adrenal androgens

**Know this pathway of the HPA Axis: Hypothalamus releases CRH --> acts on G protein coupled receptors in the anterior pituitary (on corticotroph cells) --> this causes an increase in adenylate cyclase (AC) --> this stimulates the secretion of ACTH --> ACTH uses G protein coupled receptors to get into target organs (like the adrenal cortex) and cause an increase in AC to make the target organ release hormones like cortisol or aldosterone

CRH (hypothalamus) --> GPCR on corticotroph cells of the anterior pituitary --> activates AC (AC --> cAMP --> pka) causes release of ACTH --> ACTH binds to GPCR on target cells --> again activates AC --> AC causes release of hormones by the target cells

Steroid hormones are ALL derivatives of _________________

Cholesterol! Some key steroid hormones are testosterone, estradiol (estrogen), cortisol, mineralocorticoids, and aldosterone

Hormones secreted by the pituitary gland (think acronym)

FLAT P(I)G ....MMMM -FSH, LH, ACTH, TSH, prolactin, growth hormone; MSH (melanocyte stimulating hormone) FLAT (the tropic hormones --> stimulates another gland, affects growth): *follicle stimulating hormone*, *luteinizing hormone*, *adrenocorticotropic hormone*, *thyroid stimulating hormone*; ALSO *MSH* P(I)G (the direct hormones, also affect growth): *prolactin* (acts on breast for breast growth and milk production) and *growth hormone* (acts on liver)

What are androgens?

Includes testosterone, are known for contributing to development of male secondary sex characteristics but are also found in women.

Hormones secreted by the pancreas

Insulin, Glucagon, Somatostatin

What is the role of insulin? What type of hormone is it? What endocrine gland secretes it?

It is a peptide hormone secreted by pancreatic beta cells (pancreas can be considered as an endocrine gland). It: 1. promotes storage of glucose as glycogen in the liver and muscle 2. promotes uptake of glucose and storage as triglycerides in adipose tissue and the liver.

Function of cortisol? (a steroid hormone)

It is released in response to stress and has many metabolic functions - MAINTAINS ENERGY BALANCE.

Variation/Oscillation of Hormone secretion - why is this important?

Many hormones are secreted in a pulsatile manner (based on if you've just eaten a meal, time of day/circadian rhythm, etc). This is important to note clinically because depending on when you sample for the hormone, the result you get may be totally different! Ex: cortisol peaks in the morning, growth hormone secreted overnight, insulin secreted after a meal

** Know: Neurons coming from the hypothalamus that secrete hormones onto the anterior pituitary are __________ Neurons coming from the hypothalamus that secrete hormones onto the posterior pituitary are ________

Neurons headed from hypothalamus to the anterior pituitary are SHORT --> they feed into the capillary bed that transects the hypothalamus and anterior pituitary instead of making direct contact with the anterior pituitary Neurons headed from the hypothalamus to the posterior pituitary are LONG --> they feed right into the capillaries IN the posterior pituitary

Hormone-receptor binding kinetics; kd is used instead of km. See specific binding vs nonspecific

Note - with specific binding, concentration of hormones is low and affinity is high!

Secretion of hormones by class

Peptide hormones are usually stored in vesicles and thus will need to be secreted by *exocytosis* Steroid hormones are continually released by *diffusion* Note: control occurs via *kinetic influences* on the enzymes or carrier proteins involved in the production of the hormone (ex: remember, steroid hormones are limited by the amount of carrier protein available to shuttle them around)

Hormone synthesis by hormone class (what controls their synthesis?)

Peptide hormones synthesis is: *directly, transcriptionally controlled*, and many are made as inactive precursors (zymogens) Amine AND steroid hormones synthesis is: *indirectly controlled by production of key synthetic enzymes/substrate availability*. Note - steroid hormones are limited by the amount of carrier proteins available to shuttle them around! The synthesis of ALL hormones is *highly regulated* by positive/negative feedback.

Homeostatic hormonal effects (4) ...think acronym

RE-RE...Hormones help to achieve homeostasis by controlling/assisting in: 1. REGULATION - of blood volume, osmolarity, glucose, and electrolytes 2. ENERGY BALANCE - storage and breakdown of metabolites, energy production, metabolic rate 3. REPRODUCTION - growth and development 4. ENVIRONMENTAL ADAPTATION - adapting to temperature, stress, etc.

Hormone regulation/feedback (simple and complex/hierarchical)

Simple: negative feedback in which a hormone, or response to a hormone, inhibits further hormone secretion Complex (hierarchical): negative feedback in which a hormone secreted from a primary target gland exerts negative feedback ON THE HYPOTHALAMUS OR PITUITARY GLAND. This can be short or long loop. **positive feedback is also possible

The __________ secretes CRH which then stimulates the anterior pituitary to secrete _________ which then stimulates the adrenal cortex to secrete ________, _________ and ________. What class of hormones does each belong to?

The *hypothalamus* secretes CRH (corticotropin releasing hormone), which then stimulates the anterior pituitary to secrete *ACTH* (adrenocorticotropic hormone), which then acts on the adrenal cortex to make it secrete *cortisol, aldosterone, and the androgens*. CRH and ACTH are peptide hormones, while cortisol, aldosterone and androgens are steroid hormones. The main function of CRH is to cause ACTH secretion. The main function of ACTH is to cause aldosterone, androgens and cortisol secretion.

What is the HPA axis?

The HPA axis is named after its three components: the hypothalamus, the pituitary gland, and the adrenal glands. It is a complex set of direct influences and feedback interactions among these three endocrine glands.

Hormone concentration in the blood (plasma) is affected by (3 things):

The plasma free hormone concentration is affected by: 1. the rate of hormone secretion 2. the rate of hormone elimination 3. the extent of hormone binding to plasma proteins *the magnitude of a response to a hormone depends on how many receptors are bound which in turn depends on the free hormone concentration

Function of aldosterone? (a steroid hormone)

To decrease urinary NA+ excretion and increase urinary K+ and H+ secretion. In this way, it raises blood volume and thus blood pressure.

What would be the effect of the administration of a synthetic glucocorticoid (any steroid hormone produced by the adrenal glands) on the *circulating ACTH* levels in a normal person? What would be the effect of the administration of a synthetic glucocorticoid on the *total cortisol* levels in a normal person?

both would decrease! negative feedback.

Endocrine glands are _____________, they secrete hormones into interstitial space. They (select: are or are not) connected physically.

ductless; are NOT connected physically

Three body systems important in communication

endocrine, nervous, immune system --> goal is homeostasis

Receptors and Hormones: Hormones circulate at _________ levels in the blood Hormones must then bind to receptors at __________ affinity

hormones circulate at low levels; have high affinity for their receptors