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Annie Christianus

Department of Aquaculture, Faculty of Agriculture,

Universiti Putra Malaysia

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1st record of endocrine experiments:tests on roosters in 1849 while he wascurator of the local zoo.

Chronology on Early Endocrine Studies

Ablation and replacement

Found that a rooster's comb is anandrogen-dependent structure. Followingcastration, the comb atrophies, aggressivemale behavior disappears, and it lost

interest in the hens.

However these castration-induced changescould be reversed by administration of acrude testicular extract (or prevented bytransplantation of the testes).

Courtesy: Dale Buchanan Hales,

PhD

Department of Physiology &

Biophysics

www.uic.edu.

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Claude Bernard

(1813-1878)

Stated : the endocrine system regulates theinternal milieu of an animal

The internal secretions were liberated by one

part of the body, traveled via the bloodstream to

distant targets cells. Circa 1854

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Ernest Henry Starling

(1866-1927) Discovered the functional significance of serum

proteins.

In 1902 along with Bayliss he demonstrated thatsecretin stimulates pancreatic secretion.

In 1924 along with E. B. Vernay he demonstratedthe reabsorption of water by the tubules of the

kidney.

He was the first to use the term hormone

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Charles Edouard Brown-Squard (1817-1894) scientific interest in chemical contents of testes with

his famous auto-experimentation.

In 1889, Brown-Sequard reported that he had increased

his physical strength, mental abilities and appetite byself-injection with an extract derived from the testiclesof dogs & guinea pigs

Although never substantiated, this claim prompted

researchers around the world to pursue the new field oforganotherapy

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Schafer & Hering (1906): extract of pituitary

gland from cod when injected to dog-caused

kidney dilation & diuresis

Gudernatsch (1912): feeding of horse thyroid

to juvenile tadpoles- induced metamorphose

into frog

Kopec (1922): hormone from brain control

moulting in moth

Turner (1948): 1st text book- General

Endocrinology

(Source: Matty, 1985)

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Endocrine system regulates development& growth processes in fish

(source: Reinecke et al., 2006)

Endocrine regulation involved system

integration of neuroendocrine, hormones,

homeostasis, etc.

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Endocrine system

-A complex system of glands (pituitary,pancreas, gonads, etc...)

-It produce hormones

-Endocrine system disruption can result in

adverse effect to body

-Disruptions include = disruption in thesynthesis, secretion, transport, binding,

action, maintenance of homeostasis,

reproduction, development, behavior

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Homeostasis

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Endocrine system maintains

homeostasisConcept: Hormones act on distant target cells to

maintain the stability of the internal milieu (this was

a major advance in physiological understanding)The secretion of the hormone was evoked by a changein the milieu and the resulting action on the targetcell restored the milieu to normal.

The desired return to the status quo results in themaintenance of homeostasis

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Homeostasis

~ The ability of the body or a cell to seek andmaintain a condition of equilibrium or stability

within its internal environment when dealing with

external changes

i.e.: In humans, homeostasis happens when the

body regulates body temperature in an effort to

maintain an internal temperature around 98.6

degrees Fahrenheit. For example, we sweat tocool off during the hot summer days, and we

shiver to produce heat during the cold winter

season.

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Sensing and signalingEndocrine glands

synthesize and store

hormones. These glands

have a sensing and

signaling system which

regulate the duration and

magnitude of hormonerelease via feedback from

the target cell.

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Endocrine vs. Nervous System Major communication systems in the body

Integrate stimuli and responses to changes in externaland internal environment

Both are crucial to coordinated functions of highlydifferentiated cells, tissues and organs

Unlike the nervous system, the endocrine system isanatomically discontinuous.

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Nervous system

The nervous system exerts

point-to-point control throughnerves, similar to sending

messages by conventional

telephone. Nervous control is

electrical in nature and fast.

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Hormones

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Hormones travel via the

bloodstream to target cellsThe endocrine systembroadcasts its

hormonal messages to essentially all

cells by secretion into blood andextracellular fluid. Like a radio

broadcast, it requires a receiver to get

the message - in the case of endocrine

messages, cells must bear a receptorfor the hormone being broadcast in

order to respond.

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A cell is a target because is has a specific receptor for the

hormoneMost hormones circulate in blood, coming into contact with essentially

all cells. However, a given hormone usually affects only a limited

number of cells, which are called target cells. A target cell

responds to a hormone because it bears receptors for the

hormone.

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Principal functions of the

endocrine system Maintenance of the internal environment in the

body (maintaining the optimum biochemicalenvironment).

Integration and regulation of growth anddevelopment.

Control, maintenance and instigation of sexual

reproduction, including gametogenesis, coitus,fertilization, fetal growth and development andnourishment of the newborn.

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Types of cell-to-cell signalingClassic endocrine hormones travelvia bloodstream to target cells;

neurohormones are released via

synapses and travel via the

bloostream;

paracrine hormones act on adjacent

cells and

autocrine hormones are released

and act on the cell that secreted

them.

Also, intracrine hormones act

within the cell that produces them.

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Response vs. distance traveled

Endocrine action: the hormone is distributed in blood and binds to

distant target cells.

Paracrine action: the hormone acts locally by diffusing from its

source to target cells in the neighborhood.

Autocrine action: the hormone acts on the same cell that producedit.

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Regulation of hormone secretionSensing and signaling: a biological need is sensed,

the endocrine system sends out a signal to a target

cell whose action addresses the biological need.Key features of this stimulus response system are: receipt of stimulus

synthesis and secretion of hormone

delivery of hormone to target cell evoking target cell response

degradation of hormone

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Control of Endocrine Activity

The physiologic effects of hormones depend

largely on their concentration in blood and

extracellular fluid.

Almost inevitably, disease results when hormone

concentrations are either too high or too low, and

precise control over circulating concentrations ofhormones is therefore crucial.

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Control of Endocrine Activity

The concentration of hormone as seen by target

cells is determined by three factors:

Rate of production

Rate of delivery

Rate of degradation and elimination

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Rate of production: Synthesis and secretion ofhormones are the most highly regulated aspect of

endocrine control. Such control is mediated by positive

and negative feedback circuits, as described below in

more detail.

Rate of delivery: An example of this effect is blood flow

to a target organ or group of target cells - high blood flow

delivers more hormone than low blood flow.

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Rate of degradation and elimination: Hormones,

like all biomolecules, have characteristic rates of

decay, and are metabolized and excreted from the

body through several routes.

Shutting off secretion of a hormone that has a very

short half-life causes circulating hormone

concentration to plummet, but if a hormone'sbiological half-life is long, effective concentrations

persist for some time after secretion ceases.

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Feedback Control of Hormone Production

Feedback loops are used

extensively to regulate

secretion of hormones in thehypothalamic-pituitary axis.

An important example of a

negative feedback loop is seen

in control of thyroid hormonesecretion

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Inputs to endocrine cells

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Neuroendocrine

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Neural control Neural input to hypothalamus stimulates synthesis

and secretion of releasing factors which stimulatepituitary hormone production and release

Chronotropic control Endogenous neuronal rhythmicity

Diurnal rhythms, circadian rhythms (growthhormone and cortisol), Sleep-wake cycle; seasonalrhythm

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Episodic secretion of hormones Response-stimulus coupling enables the endocrine

system to remain responsive to physiological demands

Secretory episodes occur with different periodicity

Pulses can be as frequent as every 5-10 minutes

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Episodic secretion of hormones The most prominent episodes of release occur with

a frequency of about one hourreferred to ascirchoral

An episode of release longer than an hour, but lessthan 24 hours, the rhythm is referred to asultradian

If the periodicity is approximately 24 hours, the

rhythm is referred to ascircadian

usually referred to as diurnalbecause the increase insecretory activity happens at a defined period of the day.

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Circadian (chronotropic) control

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Circadian Clock

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Physiological importance of

pulsatile hormone release Demonstrated by GnRH infusion

If given once hourly, gonadotropin secretion and

gonadal function are maintained normallyA slower frequency wont maintain gonad function

Faster, or continuous infusion inhibitsgonadotropin secretion and blocks gonadal steroid

production

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Clinical correlate Long-acting GnRH analogs (such as leuproline) have been

applied to the treatment of precocious puberty, tomanipulate reproductive cycles (used in IVF), for thetreatment of endometriosis, PCOS, uterine leiomyoma etc

Feedback control Negative feedback is most common: for example, LH from

pituitary stimulates the testis to produce testosterone which inturn feeds back and inhibits LH secretion

Positive feedback is less common: examples include LHstimulation of estrogen which stimulates LH surge at ovulation

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Negative feedback effects of cortisol

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Substrate-hormone control Glucose and insulin: as glucose increases it stimulates

the pancreas to secrete insulin

db k l f l b

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Feedback control of insulin by

glucose concentrations