ENDOCRINE. DR.HAROON RASHID.

OBJECTIVES.

• Define hormone & list the general functions of hormones in the body.

• Classify hormones according to their chemical nature.

• Outline the endocrine glands & exemplify some of their hormones.

• Describe briefly the major mechanisms for hormone actions.

• Hormone is a chemical substance secreted by ductless gland into the blood.

• Endocrine glands- • Hypothalamus, • Pituitary gland • Thyroid Gland. • Parathyroid. • Heart,Pancrease, • • •

• Adernal gland. • Testis • Ovaries etc.

Hypothalamus and posterior pituitary

Midsagital view illustrates that magnocellular neurons paraventricular and supraoptic nuclei secrete oxytocin and vasopressin directly into capillaries in the posterior lobe

What is the classical endocrine system?

We now know that nearly every tissue secretes chemical signals that act as hormones, heart, immune cells, stomach, intestines, bone cells, liver, skin, glial cells, etc.

www.cushings-help.com/ images/endocrine.jpg

What are the regulatory products of the hypothalamus?

Hormone Acronym

Hypophysial Cell Type

Hypothalamic Regulator(s) Hormonal Function(s)

Corticotropin, Adrenocorticotropin

ACTH

Corticotrope

+Corticotropin Releasing Hormone, Corticoliberin (CRH); + Interleukin 1 ; - Glucocortical Steroids (via CRH); + Vasopressin; + PACAP

Stimulates glucocorticoid production by adrenal fasiculata & reticularis

Thyrotropin, Thyroid Stimulating Hormone

TSH

Thyrotrope

-Thyroxine (T4); +Thyroid Releasing Hormone, Thyroliberin (TRH); -Somatostatin (SS)

Stimulates thyroxine production by thyroid

Prolactin, Mammotropin, Luteotropin

PRL

Lactotrope; Mammotrope

-Dopamine; + TRH; - SS; + Estrogens; + Oxytocin Stimulates milk synthesis by secretory epithelium of breast; supports corpus luteum function

Somatotropin, Growth Hormone

GH

Somatotrope

+ Growth Hormone Releasing Hormone, Somatoliberin (GHRH); - SS; + PACAP

Stimulates somatic growth, supports intermediary metabolism

Follitropin, Follicle Stimulating Hormone

FSH

Gonadotrope

+ Gonadotropin Releasing Hormone, Luteinizing Hormone Releasing Hormone, Gonadoliberin (GnRH, LHRH); - Inhibin; - Sex steroids (via LHRH)

Supports growth of ovarian follicles & estradiol production; Supports Sertoli cell function & spermatogenesis

Lutropin, Luteinizing Hormone

LH

Gonadotrope

+ GnRH (LHRH); - Sex steroids (via LHRH in & ); + Estradiol in near midcycle

Supports late follicular development, ovulation, & corpus luteum function (especially progesterone synthesis); Supports testosterone synthesis, Leydig cell

Melanotropin, Melanocyte Stimulating Hormone

MSH

Melanotrope

+ CRH Supports dispersal & synthesis of pigment in melanocytes; may alter adrenal response to ACTH

What are endocrine systems for?

Endocrine Functions• Maintain Internal Homeostasis • Support Cell Growth • Coordinate Development • Coordinate Reproduction • Facilitate Responses to External Stimuli

ENDOCRINOLOGY• Two systems control all physiologic processes:• The nervous system exerts point-to-point control

through nerves, similar to sending messages by conventional telephone. Nervous control is electrical in nature and fast.

• The endocrine system broadcasts its hormonal messages to essentially all cells by secretion into blood and extracellular fluid. Like a radio broadcast, it requires a receiver to get the message - in the case of endocrine messages, cells must bear a receptor for the hormone being broadcast in order to respond.

Endocrinology

Hormones:Classification:I.-Based on distance of target cells:1.Pracrine 2.Autocrine3.IntracrineII.Based on chemical nature:1.Peptides 2. Steroids 3.Derivatives of AA

Biosythesis

1.Peptide hormones:Gene-mRNA-AA linkage- Polypeptide chains

( preprohormone)- removal of signal peptide- formation of prohormone-to-Golgi apparatus – stored as secretory granules and are released by exocytosis( ca+ mediates ?)

2. Steroids:Cholesterol to hormone and released ( note: NOT STORED)

1.Peptide hormones:

ER,Golgi,secretoryvesicles

Many hydrophobic (lipophilic) hormones are steroids,derived from cholesterol

Storage

• Steroids: not stored.• Peptides: to some extent• Thyroids: reserve of upto 3 months.

• DEGRADATION:• Usually by Liver & excreted by kidneys.• Some are inactivated by kidneys.

Transport in blood

1. Protein-peptides & catacholamines:water soluble & are transported in blood.

2. Steroids & Thyroid hr: insoluble in water, but when combine with proteins- become water soluble and are transported. A small portion of hydrophobic hormones remain free( un bound with proteins ) and this fraction is metabolically active. The bound form acts as reservoir.

Control of hormone secretion( = Secretion can be stimulated or inhibited)

• Other hormones(of Hypothalamus or Ant.pituitary )• Feed back mechanisms- + feedback&-ve• Stress• Biological rhythm• Neural and mental activity• Plasma concentrations of ions or nutrients, as well as binding

globulins • Environmental changes, e.g., of light or temperature • One special group of hormones is the tropic hormones that

stimulate the hormone production of other endocrine glands. For example, thyroid-stimulating hormone (TSH) causes growth and increased activity of another endocrine gland, the thyroid, which increases output of thyroid hormones.

• Others.

Regulation

• Positive feedback mechanism-Release of oxytocin during Lactation-Contraction of myoepitheial cells-Release of Milk.

• Negative feedback mechanism-Decrease in concentration of hormone will stimulate the target gland-Release of hormone occurs.

• Eg-Thyroid,Insulin etc.

NEGATIVE FEEDBACK

Mechanism of action: mainly by RECEPTORS

• Receptors:1. Only target cells have receptors.2. Only fraction of total population of receptors in target cells is enough

for max.effects( Insulin 10% )3. Receptors combine with ligands and initiate series of

actions( Ligand=chemical molecule which combine with receptor, it can be hormone, neurotransmitter,drug)

4. There is upregulation & down regulation.5. A cell may have many different types of receptors for different

sub/hormones( eg. Oxyntic cells have receptors for Ach, histamine, prostaglandins)

6. Receptors are degraded and are replaced.7. Location: MEMBRANE BOUND OR CYTOSOLIC/NUCLEAR8. RECEPTOS : may be linked to- ionic channels of membrane,Gproteins,

enzymes in the cells,may stimulate transcripting mechanism.

Types of receptors

G-protein coupled receptorsAdenylate cyclase, cAMP and PKA

Types of receptors-

Mechanism of Action of hormones

• For many hormones, including most protein hormones, the receptor is membrane associated and embedded in the plasma membrane at the surface of the cell. The interaction of hormone and receptor typically triggers a cascade of secondary effects within the cytoplasm of the cell, often involving phosphorylation or dephosphorylation of various other cytoplasmic proteins, changes in ion channel permeability, or increased concentrations of intracellular molecules that may act as secondary messengers (e.g. cyclic AMP). Some protein hormones also interact with intracellular receptors located in the cytoplasm or nucleus by an intracrine mechanism.

Mechanism of Action of hormones

• For many hormones, including most protein hormones, the receptor is membrane associated and embedded in the plasma membrane at the surface of the cell. The interaction of hormone and receptor typically triggers a cascade of secondary effects within the cytoplasm of the cell, often involving phosphorylation or dephosphorylation of various other cytoplasmic proteins, changes in ion channel permeability, or increased concentrations of intracellular molecules that may act as secondary messengers (e.g. cyclic AMP). Some protein hormones also interact with intracellular receptors located in the cytoplasm or nucleus by an intracrine mechanism.

Cell surface receptor action

Second messenger systems The generation of second messengers and activation

of specific protein kinases results in changes in the activity of the target cell which characterizes the response that the hormone evokes.

Changes evoked by the actions of second messengers are usually rapid

Second messenger systems Each of these second messenger systems activates a

specific protein kinase enzyme. These include cyclic nucleotide-dependent protein

kinases Calcium/calmodulin-dependent protein kinase,

and protein kinase C which depends on diacyl glycerol binding for activation. Protein kinase C activity is further increased by

calcium which is released by the action of inositol phosphates.

Second messengers for cell-surface receptors

Second messenger systems include: Adenylate cyclase which catalyzes the conversion of ATP to

cyclic AMP; Guanylate cyclase which catalyzes the conversion of GMP

to cyclic GMP (cyclic AMP and cyclic GMP are known collectively as cyclic nucleotides);

Calcium and calmodulin; phospholipase C which catalyzes phosphoinositide turnover producing inositol phosphates and diacyl glycerol.

Mechanism of Action of hormones

• For hormones such as steroid or thyroid hormones, their receptors are located intracellularly within the cytoplasm of their target cell. In order to bind their receptors these hormones must cross the cell membrane. The combined hormone-receptor complex then moves across the nuclear membrane into the nucleus of the cell, where it binds to specific DNA sequences, effectively amplifying or suppressing the action of certain genes, and affecting protein synthesis.[2] However, it has been shown that not all steroid receptors are located intracellularly, some are plasma membrane associated.[3]

Mechanism of lipid soluble hormone action

Effects of hormone• Hormone effects vary widely, but can include:• stimulation or inhibition of growth, • In puberty hormones can affect mood and mind • induction or suppression of apoptosis (programmed cell death) • activation or inhibition of the immune system • regulating metabolism • preparation for a new activity (e.g., fighting, fleeing, mating) • preparation for a new phase of life (e.g., puberty, caring for offspring,

menopause) • controlling the reproductive cycle • In many cases, one hormone may regulate the production and release of

other hormones• Many of the responses to hormone signals can be described as serving to

regulate metabolic activity of an organ or tissue.

Estimation of hormones

• Calorimetric• Bioassay• RIA• ELISA• Chemiluminescence method.