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. AMINES -

o Oxytoxin Long polypeptides o GH o Insulin

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.

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

GLYCOPROTEINS Pituitary hormones ( FSH, LH, TSH)

ENDOCRINE ORGANS One characteristic is that it is highly vascular.

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

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

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 & IP3 Steroids, T3 & T4, - Bound in protein NE & E beta - Receptors: Cytoplasm and nucleus - Slow rate of excretion - Enhance oxidative metabolism

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

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 its 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= inactive o 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, were always hungry, well 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-cells o 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 Autonomics o Behavior ( excess testosterone- anger) o Reproduction ( gonadotrophin) More receptor, effect is more potentiated. Up regulation of receptors o Few hormones Down regulation o More hormone o 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 amine o 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 calciumcalmodulin 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 dati o It increases fat metabolism o 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 theres 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 exercise o 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 control o 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 Epinephrine o Act together o Thyroglobulin wont 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.

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..

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.

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 gland o Medulla = neural o Zona Glomerulosa= only partly regulated by HHS axis o Pineal gland o Thyroid o Parathyroid

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

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

of liver and kidney which will cause unreleased/ not secreted hormone.

METABOLISM OF HORMONES STEROID Converted to water soluble component and excreted in the kidney. Enzymatic degradation Recirculation/ diffusion Re-uptake

BIOGENIC AMINE Enzymatic degradation o COMP o 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 -> 5dihydrotestostetone (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