Introduction to endocrine

PARTLY ENDOCRINE

Cardiovascular system

- Partly endocrine- Right atrium releases ANP that will regulate your

kidney function - ANP acts by secreting Na2+ so that Na2+ will

decrease in the body.- Na2+ makes your urine hypertonic and it will

attract water.

Stomach and small intestine

- Secretes glucagon and secretin (parahormone), CCK

HORMONES

- Secreted by a particular cell then goes into the blood vessel.

- Receptors are far from the site of secretion

ENDOCRINE ORGANS

- One characteristic is that it is highly vascular.

PARAHORMONE

- Para means beside- Receptors are found in the adjacent cell.

GENERAL HORMONE

- Effect is usually systemic

LOCAL HORMONES

- The effect is less systemic and more localized.

TYPES OF HORMONES

- Amines / derivatives of tyrosine- Polypeptide- Steroid hormone- Glycoproteins- Cytokines

POLYPEPTIDES

- Could be long or short- Short polypeptides

o ADH

o Oxytoxin- Long polypeptides

o GHo Insulin

AMINES

- From tyrosine- Dopamine, thyroid hormone, cathecolamines

( NE & E) are amines.

STEROID

- From cholesterol- Estrogen, progesterone, testosterone, cortisol.- Mineralocorticoids ( aldosterol)- Lipids has same component like the cell

membrane and because of that, they can easily penetrate the cell membrane.

- Receptors are in the cytoplasm or nucleus.- The effect is slow compare to membrane

receptors.

GLYCOPROTEINS

- Pituitary hormones ( FSH, LH, TSH)

RECEPTORS

- Could be found inside the cell membrane or inside the cytoplasm or nucleus.

MEMBRANE RECEPTOR

- Most peptide and some amine particularly NE & E acts on alpha receptors ( CAMP)

- Rate of excretion of polypeptide are high than steroid hormone.

- In plasma, your NE & E (alpha) are free while steroid is commonly bound

NE & E alpha - Free in plasma- Receptors: Cell

membrane- Fast rate of

excretion- Phospholipase C->

DAG & IP3Steroids, T3 & T4, NE & E beta

- Bound in protein- Receptors: Cytoplasm

and nucleus- Slow rate of excretion- Enhance oxidative

metabolism

INTRACELLULAR RECEPTORS

- Found inside the cytoplasm (intracytoplasmic)- Or it could be in the nucleus (intranuclear)=>

more common.- Example are steroid hormone or amine ( thyroid

hormone, inactivator)- If it’s inside the cytoplasm, the hormone

receptor-complex will go inside the nucleus to regulate or modify your activity.

- Slow effect since when it goes inside the cell, gene modification is done. (testosterone).

CHARACTERISTICS

- It must be secreted and produced by chief cell.- It should be hypo or hyper secretion.- It should be digested by human enzyme.

o Remember you have degradation or removal of your hormone.

o One will be reacting; another one is enzymatic degradation, and lastly diffusion.

o This is the reason why when hormones are induced orally, they are ineffective. i.e. insulin

o They are enzymes in the GIT that immediately degrade insulin.

- It can influence cellular activity but they do not begin or commence a particular cellular activity.

o It is the reason why insulin has low levels if not we will need insulin for 24/7.

- They will regress or enhance.- They are not secreted continuously but in a

pulsatile function.- They can be effective even in a very low

concentration.- They are very good in enhancing metabolic

functions of some enzymes.- Effects are normally directed at specific cells

where it has its receptors.- They are directly secreted in the blood. It can be

bound or unbound.o Bound in the protein= inactiveo Unbound / free to protein = active

- Usually, they bind to proteins reversibly as well as bind to your receptor reversibly.

- If binding is irreversible, the hormone has a longer effect or the effect is forever.

o Insulin if bound to a receptor in fat cell, we will get fatter. We will need more glucose since it will let the glucose enter the skeletal muscle.

o We cannot regulate it, we’re always hungry, we’ll always eat because of low blood glucose if we always have insulin.

- You can store hormones in the circulation. o Insulin is stored in your pancreatic islet

/ beta-cellso Cortisol are being stored and secreted

in your adrenal cortex.o ADH and Oxytocin are stored in the

posterior pituitary.- Hormones are only released when needed- Pulsing agents present in the plasma.

o Testosterone, estrogen, progesterone.- We have steroid binding globulin but we also

have albumin that will bind to your receptor.- Secreting cell -> blood stream -> target cell

(receptor).- NO receptor NO effect! But they could also have

an effect in the non-endocrine cells.- Hormones are needed for homeostasis.- It is also needed for morphogenesis in order for

us to grow. ( slowed / lowered in plasma as we age).

o From menarche to meopause- Regulates some neural activity

o Autonomicso Behavior ( excess testosterone- anger)o Reproduction ( gonadotrophin)

- More receptor, effect is more potentiated.- Up regulation of receptors

o Few hormones- Down regulation

o More hormoneo Less effective

- Action of hormone to membrane receptor-> opening of channel-> change of permeability of the membrane or it can promote changes inside the cell ( G-protein, cyclic nucleotide other are direct).

o Polypeptide or amineo Polypeptide that can act on the

membrane and promote intracellular changes -> insulin, GH, prolactin, leptin?, angiotensin.

- Madaming hormone, bababa ang number ng hormone receptor

- Kapag unti ang hormone, dadami ang receptor at regulation

SIGNAL TRANSDUCTION

- In peptides, most signal transduction mechanism are in the membrane via activation of calcium-calmodulin system, metabolic enzyme or activation of JAK enzyme or activation of membrane receptors that will generate second messenger ( CAMP, CGMP etc).

- Other peptides acts on phospholipase C to generate DAG & IP3 as second messenger.

- Generation of arachidonic acid for activation of second messenger

- Other amines receptors acts with nuclear receptor to enhance oxidative metabolism.

- NE & E on thyroid hormone increases metabolic activity

o Pampapayat datio It increases fat metabolismo Side effects: activates cardiac receptor

which causes arrhythmia.o Payat k nga, patay k naman..

- Ligand binds to receptor-> activate G protein-> opening of channel (metabotrophic).

- If the receptor is in the channel itself, it is ionotrophic.

- Activation by Ca2+ where it can act as second messenger -> activate kinase -> effect

- If G-protein is activated, it can produce cyclic messenger such as CAMP, CGMP that will activate protein kinase.

- CAMP will activate protein kinase A- CGMP will activate protein kinase G- Phospholipase C will activate protein kinase C- When there’s a binding in the ligand, there will

be a detachment of beta, gamma and alpha which all has a binding site.

- To activate, you either open Ca channel or produce second messenger.

DEPHOSPHORYLATION & PHOSPHORYLATION- Phosphorylation of an enzyme : active- Dephosphorylation: inactive- i.e. Myosin

o myosin kinase activates myosin- Phospholamban

o If activated myosin is inactivated

- When is testosterone increased?o Endogenous testosterone has greater

effect that exogenous.o Must be produced before exerciseo Masturbate before exercise.

- Ejaculate is rich in protein, fortified with ascorbic acid, zinc. It is highly nutritious but it has high cholesterol.

REGULATION OF HORMONES IN PLASMA

- Glucose, cholesterol, ions or electrolytes.- Regulation of physiologic response via negative

feedback or modified negative feedback.- It can also be regulated by neurons by direct

neural controlo Oxytocin

Suckling will stimulate the nerve -> hypothalamus -> secrete oxytocin via post. Pituitary.-> mammary area-> contraction of myoepithelial cell-> milk let down

It is milk let down not milk secretion because milk secretion is a function of prolactin.

o ADH- It is regulated by other hormones

o Alpha cells regulated by insulin to secrete glucagon

o Insulin has antagonistic effect to glucagon.

- Thyroid hormone and Epinephrineo Act togethero Thyroglobulin won’t act without

epinephrine.

ANTAGONISTIC HORMONE

- Insulin & glucagon- Insulin will decrease the blood glucose that will

cause the stimulation of glucagon.- Glucagon will increase blood sugar so that an

increase in blood sugar will stimulate insulin to decrease sugar.

REGULATION BY DIRECT CONTROL

- Adenohypophysis- Positive feedback - Modified negative feedback

SHORT LOOP

- Pituitary to hypothalamus is inhibited.- Negative feedback

LONG LOOP

- Endocrine organ is inhibited that will cause inhibition of pituitary and hypothalamus.

POSITIVE FEEDBACK

- Stimulation of hypothalamus for releasing hormones -> stimulate adenohypophysis-> stimulate thyroid stimulating hormone -> stimulate thyroid hormone

- Best example is estrogen secretion- Another example is GnRH-> stimulate anterior

pituitary-> release FSH -> target organ is ovary-> the ovary will secrete estrogen -> increase in estrogen will further stimulate anterior pituitary to further release FSH

- Habang pataas ng pataas ang estrogen, madaming estrogen ang masesecreate tpos magsesecrete ng LH para may estrogen at progesterone ka na.

- LH lang ang magiinhibit sa estrogen at progesterone?

- Initially this process is positive feedback why? o As long as you release estrogen-> there

will be an increase in FSH-> until LH increase-> ovulation occurs -> estrogen is produced, by this time, instead of positive feedback, negative feedback will occur.

- Birth giving-> uterus contract due to oxytocin -> stretch in uterus cause increase in oxytocin until you gave birth. It will only decrease when birth giving is done.

NEGATIVE FEEDBACK

- Hypothalamus -> hypophysis -> target endocrine organ

o If negative feedback: hypothalamus will release releasing hormones -> it will act on the pituitary gland as stimulating hormone -> stimulating hormone will act on target endocrine gland -> release hormones -> increase in hormones will inhibit hypothalamus, adenohypophysis

THYROID HORMONES

- Follows negative feedback also known as endocrine acted/ driven negative feedback

- Not always increase because excess will cause tachycardia, decrease body wt., laging dilat (parang adik), nanginginig lagi kht wlang gngawa, mabilis takbo ng utak, you will have arrhythmia until you die.

- If thyroid level decreases, you will still stimulate ant. Pituitary and hypothalamus.

o What inhibits hypothalamus? – increase T3&T4, TSH

o What inhibits ant. Pituitary? – increase T3 & T4

- Secretion of hormones follow a diurnal pattern : morning and afternoon.

o Steroid hormone ( 8am and 6pm) = kaya sa umaga by 8 am ihi ka ng ihi..

PHYSIOLOGIC DRIVEN NEGATIVE FEEDBACK

- Insulin and Glucagon- increase in blood glucose -> secrete insulin in

pancreatic beta cell- continuous increase in insulin will decrease

blood glucose-> inhibit insulin secretion-> stimulate glucagon secretion

PART OF ENDOCRINE SYSTEM THAT IS NOT INCLUDED IN HHS AXIS

- Adrenal glando Medulla = neuralo Zona Glomerulosa= only partly

regulated by HHS axiso Pineal glando Thyroido Parathyroid

HORMONE INACTIVATION

- inactivation of hormone is generally in the liver but it is not absolute since we have other hormone that is not degraded in the liver instead, it is degraded/ catabolized on the site of its action.

- When it is catabolized, it is commonly excreted in the kidney but it is not also absolute since we can also excrete it via GIT or skin.

- When destruction of liver occurs, will lead to non-metabolized hormone but it will still have effect.

- Destruction of kidney will lead to non-excretion of drugs and hormones

METABOLISM OF HORMONES

- Enzymatic degradation- Recirculation/ diffusion - Re-uptake

STEROID

- Converted to water soluble component and excreted in the kidney.

BIOGENIC AMINE

- Enzymatic degradationo COMPo MAO

- Re-uptake

KIDNEY

- When hormone is secreted by endocrine cell-> it can be excreted or inactivated by metabolism, enzymatic degradation, catalyze the formation of active hormone

o Testosterone -> release by leydig cells-> catalyzed by 5-alpha- reductase -> 5- dihydrotestostetone (more active form of testosterone)

- Hormones become more active when catabolized.

- Destruction of cell itself= no hormone/ deficient in hormone. The problem is manifested in the target cell.

o Either decreased, low, or no target receptor or unresponsive/ resistance receptor.

- Increase in binding protein is the problem of the liver -> liver will continuously produce binding protein.

- Binding of protein with hormone renders it inactive

- Hypersecretion may be caused by a tumor in the endocrine organ. It may be also caused by an

increased in the receptor organ which is very responsive to the hormone-> increase sensitivity to the receptor. Less binding proteins means there is free hormone. It could be also a problem of liver and kidney which will cause unreleased/ not secreted hormone.