endocrine system

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S.SHIVA (BTEC HND IN BIO MEDICAL SCIENTIST) The Endocrine System

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Page 1: Endocrine System

S.SHIVA (BTEC HND IN BIO MEDICAL SCIENTIST)

The Endocrine System

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What is Hormone? A regulatory substance and chemical messenger

released by one cell to regulate another cell. Delivered through endocrine, neuroendocrine, neurocrine, paracrine, autocrine system to act on the target cells.

Some hormones affect on many tissues:

Eg: Growth hormone, Thyroid hormone & Insulin.

Some affect on specific tissues (Target tissues):

Eg: Thyroid stimulating hormone (TSH)

Adrenocorticotropic hormone (ACTH)

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Condt.. Endocrine: Endocrine hormones travel via blood

stream to target cells.

Neurocrine: Neurocrine hormones released via synapses and travel via blood stream.

Paracrine: Paracrine hormones acts on adjacent cells.

Autocrine: Autocrine hormones acts on the cell that secreted them.

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Distance of Travelled Hormone

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Principles of Hormone Need to maintain Homeostatic level.

Regulation of growth and development.

Control and maintenance of reproduction including fertilization and fetal growth and nourishment and development of the newborn.

Regulation of the metabolism.

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Endocrine System

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General principle of Endocrinology

The glands of internal secretion. End = Into

Crin = Secrete

The body’s great 2nd controlling system which is controlled metabolic activity of cells by hormones.

A ductless gland composed of epithelial cells, that secreted hormones directly into extracellular fluid.

From the ECF the hormones diffuse into the bloodstream.

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Cond.. Central Endocrine glands

1. Pineal gland

2. Hypothalamus

3. Pituitary gland

Peripheral Endocrine glands

4. Thyroid

5. Parathyroid

6. Thymus

7. Adrenal glands

8. Pancreas

9. Gonads (Ovaries & Testes)

Other tissues and organs that produced hormones – adipose cells, cells of the small intestine, stomach, kidneys, and heart.

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Chemistry of hormones can be..

Proteins and Polypeptides: Hormones from anterior and posterior pituitary, Pancreas, parathyroid gland. Usually released into blood stream via exocytosis.

Steroid hormones: Hormones from adrenal cortex, ovaries and testes. These are usually synthesized from cholesterol.

Amine hormones: Thyroid and adrenal medullary hormones. They are derived from tyrosine.

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Condt..

Hydrophilic and Lipophobic Peptide – work via a second messenger

Adenylate cyclase

ATP 2,3 cAMP

Catecholamines – via 2nd messengers.

Hydrophobic Thyroxine Steroid

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A structural classification of hormones

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Synthesis of hormones (Protein)

1. In the nucleus, the gene for hormone transcribed into mRNA.

2. The mRNA transferred to cytoplasm and translated on ribosome of ER to the first protein(peptide chain) product a preprohormone.

3. The chain is directed into the ER lumen by a signal sequence of amino acids.

4. The enzyme of ER cleaved the signal sequence, to create an inactive prohormone.

5. The prohormone passes from the RE through the golgi apparatus.

6. And prohormone bud off the Golgi.

7. Secretory vesicles containing enzyme which is cleaved the prohormone into one or more active peptides.

8. The secretory vesicle releases its contents by exocytosis into extra cellular space.

9. The hormone moves into the circulation for transport to its target.

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Steroid Hormones•Are not packaged, but synthesized and immediately released.

•All are derived from cholesterol. These are located in mitochondria and smooth ER.

•Steroids are lipid soluble and thus are permeable to membranes so are not stored in cell.

•Steroids hormones are not water soluble so have to be carried in the blood complexed to specific globulins.

•Corticosteroid binding globulin carries cortisol.

•Sex steroid binding globulin carries testosterone and estradiol.

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Types of steroids Glucocorticoids: cortisol is the major

representative in most mammals.

Mineralocorticoids: aldesterone being most prominent.

Androgens: such as testosterone.

Estrogen: including estradiol, and estrone.

Progestogens: ( also known a progestins) such as progesterone.

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Amine hormones

•Two types of hormones derived from the amino acid tyrosine.

Thyroid hormones and Catecholamines

•Thyroid hormones are basically a “double” tyrosine with the critical incorporation of 3 or 4 iodine atoms.

•Thyroid hormone is produced by the thyroid gland and is lipid soluble.

Catecholamine hormones

•Catecholamines both are both neurohormones and neurotransmitters.

•These include epinephrine and norepinephrine both are produced by adrenal medulla and both are water soluble.

•Secreted like peptide hormones.

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Condt..

Two other amino acids are used for synthesis of hormones:

Tryptophan is precursor to serotonin and the pineal hormone melatonin.

Glutamic acid is converted to histamine.

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Hormones and their receptors

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Hormone Transport In Blood•Most water soluble hormones circulates in plasma in free, unattached form.

•Most lipid soluble hormones bind to transport proteins to be carried in blood.

•Protein and peptide hormones, such as insulin, will be destroyed by digestive enzymes and must be given by injection.

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Mechanism of Hormone action Hormones bind and activate their specific receptors in two different ways.

Steroid hormones and thyroid affect cell function by binding and activating an intracellular receptor( usually in nucleus).

Water soluble hormones alter cell function by activating plasma membrane receptors.

After a water soluble hormones is released from an endocrine gland, it circulates in the blood, reaches a target cell, and brings a specific message to that cell.

The plasma membrane is 1st messenger.

A 2nd messenger needed to relay the message inside the cell where hormone-stimulated take place. 2n messenger is cyclic AMP (cAMP)

G-proteins are a common feature of the most second messenger system.

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Condt.. Cyclic AMP does not

directly produce a particular physiological response, but instead activates one or more enzymes known as protein kinases.

The responsiveness of target cell to a hormone depends on the hormone’s concentration and the number of receptors.

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Steroid (Water insoluble) Hormone Transport Most water- soluble hormones circulate in plasma in a free, unattached form.

Most lipid- soluble hormones bind to transport protein to be carried in blood.

The transport proteins improve the transportability of lipid soluble hormones by making them temporarily water soluble, retard the passage of the hormone through the kidney filter and slowing the rate of hormone loss in urine. And provide reserve of hormone already present in hormone.

Protein and peptide hormones, such as insulin, will be destroyed by digestive enzymes and must be given by injection.

Lipid soluble hormones bind and activate receptors within cell.

The activated receptors then alter gene expression to form of the new protein.

The new proteins alter the cells activity and affect in the physiological responses of those hormones.

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Protein (water soluble) Hormone Transport Water soluble hormones binds on the plasma receptor to alter the cell function.

The cell membrane receptor is 1st messenger.

2nd messenger is released when hormone stimulates response takes place inside of cell.

Typical action of water soluble hormones are using cyclic AMP as the 2nd messenger.

Firstly the hormone bind to the membrane receptor.

The activated receptor activate s the membrane G-protein which turns on adenylate cyclase.

Adenylate cyclase converts ATP into cyclic AMP which activate protein kinase.

Priotein kinases phosphorilated enzyme which catalyze reaction produce the physiological response.

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Condt..

The cholera toxin modifies G-proteins in intestine epithelial cells so they become locked in an activated

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Regulation Of Hormone Hormone secretion is

controlled by homeostatic feedback.

Negative feed back mechanisms that reverse the direction of a change in physiological system.

Positive feedback – (Uncommon)

Mechanisms that amplify physiological changes.

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Prostaglandins Prostaglandins (PGs) are powerful substances found in a

wide variety of body tissues.

It is a local regulator(Paracrine Signals) of hormone.

PGs are often produced in a tissue and diffuse only a short distance to act on cells in that tissue.

Several classes of PGs include prostaglandinA, prostaglandin E and prostaglandin F

Pgs influence many body functions, including respiration, blood pressure, gastrointestinal secretions, and reproduction.

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Control of Endocrine System

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Central Endocrine System Hypothalamus : receives information from the nervous system

and initiates responses through the endocrine system.

Pituitary: Attached to the hypothalamus. Composed of posterior pituitary and anterior pituitary.

Pineal Gland: Pineal gland is located just posterior to the 3rd ventricle in the brain.

Secrete Melatonin – regulates circadian rhythms. May induce sleep May initiate puberty May inhibit ovulation/ spermatogenesis May slow aging May enhance immunity

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Pituitary Gland

Anterior pituitary gland; name of hormones:

TSH – Thyroid stimulating hormonesACTH – Adrenocorticotropic hormoneFSH – Follicle stimulating hormoneLH – Luteinizing hormoneGH – Growth hormoneProlactin

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Functions of Hormones TSH – stimulate growth of thyroid gland, also

stimulate it’s hormone secretion.

ACTH: stimulates growth of the adrenal cortex and stimulate it to secrete glucocorticoids (mainly cortisol)

FSH – initiates growth of ovarian follicles each month in ovary and stimulates one or more follicles to develop to the stage of maturity and ovulation.

FSH also helps to secretion of estrogen by developing follicles and stimulate sperm production in male.

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Condt.. LH – acts with FSH to stimulate estrogen secretion and follicle

growth to maturity. Stimulate the progesterone secretion by corpus luteum. And stimulate the testosterone in the male.

GH – Stimulates growth by accelerating anabolism; also accelerates fat catabolism and slows glucose catabolism; by slowing glucose catabolism, tends to increase blood glucose to higher than normal level (hyperglycemia)

Hyper secretion during childhood results in gigantism and during adult hood results in acromegaly.

Hypo secretion during child hood results in pituitary dwarfism.

o Prolactin – stimulates breast development during pregnancy and secretion of milk after the delivery of baby.

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Posterior Pituitary gland Name of hormones:

- ADH – Antidiuretic hormone : Hypo secretion causes diabetes insipidus, characterized by excessive volume of urine.

- OT – Oxytocin

Funtion Of Hormone ADH – accelerate water reabsorption from urine in the

kidney tubules into the blood, thereby deceasing urine secretion.

Oxytocin – stimulate the pregnant uterus to contract; may initiate labor; causes glandular cells of breast to release milk into ducts.

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Control of Pituitary : Negative feedback

Target organ hormone level inhibits release of tropic hormones.

Positive feedback : Stretching of uterus

OT release, causes more stretching of uterus, until delivery.

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Pituitary Disorders Hypersecretion of growth hormone

○ Acromegaly- Middle – aged adult- Abnormal growth of the hands/feet- Bone changes alter facial features including the apacing of

teeth- Arthritis- Thick, coarse, oily skin, skin tags, enlarge lips, nose and

tongue- Deepening of the voice due to enlarged sinuses and vocal

cords; snoring due to upper airway obstruction- Excessive sweating and skin odor- Enlargement of body organs, including the liver, spleen,

kidneys and heart- Thickening of the bones and soft tissues- Problem in childhood or adolescence - gigantism

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Hypothalamus Regulates the activity of the nervous and endocrine systems.

Highest level of endocrine control Secretes regulatory hormones that control the anterior pituitary gland. Release hormones at the posterior pituitary gland. Exerts direct neural control over the endocrine cells of the adrenal medullae.

Actual production of ADH and oxytocin occurs in the hypothalamus.

After production in the hypothalamus, hormones pass along axons into the pituitary gland.

The secretion and release of posterior pituitary hormones is controlled by nervous stimulation.

The hypothalamus controls many body functions released to homeostasis (temperature, appetite, and thirst)

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Hypothalamic Hormones

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Thyroid Gland Names of Hormones:

Thyroid Hormone – Thyroxin (T4)

Triiodothyronine (T3) Calcitonin (CT)

Function of Hormone Thyroid Hormones : Accelerate catabolism (increase the body’s metabolic rate) Calcitonin – decreases the blood calcium concentration by inhibiting breakdown of bone,

which would release calcium into blood.

Hyperthyroidism ( hyper secretion of thyroid hormones) increases metabolic rate. ○ Characterized by restlessness and exophthalmoses ( protruding eyes)○ Graves disease is an inherited form of hyperthyroidism.

Hypothyroidism (hypo secretion of thyroid hormones)○ May result from different condition○ Simple goiter – painless enlargement of thyroid causes by dietary deficiency of iodine ○ Hypo secretion during early development may result in cretinism (retardation) and during

adulthood in myxedema ( characterized by edema and sluggishness)

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Thyroid Gland Disorders Congenital hypothyroidism

○ Abnormal bone development, thickened facial features, low temperature, brain damage, lethargy

Myxedema (adult hypothyroidism)○ Low metabolic rate, sluggishness, sleepiness,

weight gain, constipation, dry skin and hair, cold sensitivity, high blood pressure and tissue swelling

Endemic goiter (enlarge thyroid gland)○ Iodine deficiency, no TH, no – feed back, high TSH

Toxic goiter ( graves disease)○ Antibodies mimic TSH, high TH, exophthalmos

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Parathyroid Gland

Name of HormonePTH - Parathyroid hormone

Function of Hormone Increase blood calcium concentration by

increasing the break down of bone with the release of calcium into the blood.

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Parathyroid Disorders

Hypoparathyroid○ Surgical excision during thyroid surgery○ Fatal tetany 3-4 days

Hyperparathyroid○ Tumor in gland○ Causes soft, fragile and deformed bones○ High blood calcium○ Renal calculi

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Adrenal Gland Names of Hormones (Corticoids)

○ Glucocorticoids (GCs) – Chiefly cortisol ○ Mineralocorticoids (MCs) – Chiefly aldosterone○ Sex hormones – small amount of male

hormones (androgens) secreted by adrenal cortex of both sex.

Three cell layers (ZONES)○ Outer layer – secreted mineralocorticoids○ Middle layer – secretes glucocorticoids○ Inner layer – secretes sex hormones

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Functions of Hormones Mineralo corticoids :

Increase blood sodium and decrease body potassium concentration by accelerating kidney tubule.

Reabsorption of sodium and excretion of potassium.

Function of glucocorticoids : Help maintain normal blood glucose concentration by increasing

gluconeogenesis.

Gluconeogenesis – the formation of new glucose from amino acids produced by breakdown of proteins, mainly those in muscle tissue cells; also the conversion to glucose of fatty acids produced by the breakdown of fats stored in adipose tissue cells.

Play an essential part in maintaining normal blood pressure – make it possible for epinephrine and norepinephrine to maintain a normal degree of vasoconstriction, a condition necessary for maintaining normal blood presure.

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Adrenal Gland Act with epinephrine and norepinephrine to produce an

anti inflammatory effect, to bring about normal recovery from inflammations of various kinds.

Produced anti-immunity, anti allergy effect ; bring about a decrease in the number of lymphocytes and plasma cells and therefore a decrease in the amount of antibodies formed.

Secretion of glucocorticoid quickly increase when the body is thrown into a condition of stress; high blood concentration of glucocorticoids, in turn, brings about many other stress responses.

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Adrenal Gland

Adrenal medulla○ Names of hormones – epinephrine (Epi) , or

adrenaline, and norepinephrine (NR)

○ Functions of Hormones Helps the body resist stress by intensifying and

prolonging the effect of sympathetic stimulation.

Increased epinephrine secretion is the 1st endocrine response to stress.

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Adrenal Gland Adrenal abnormalities

○ Hypersecretion of glucocorticoids causes Cushing syndrome – moon face, hump on back, elevated blood sugar levels, frequent infection.

○ Hypersecretion of adrenal androgens may result from a virilizing tumor and cause masculinization of affected women.

○ Hyposecretion of cortical hormones may result in Addison disease ; muscle weakness, reduced blood sugar, nausea, loss of appetite, and weight loss.

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Adrenal disorders

Cushing Syndrome

Addison Disease Masculinization

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Pancreatic Islets

Names of Hormone○ Glucagon – secreted by alpha cells○ Insulin – secreted by beta cells

Function of Hormones○ Glucagon increases the blood glucose level by

accelerating liver glycogenolysis (conversion of glycogen to glucose)

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Functions of Hormone Insulin decreases the blood glucose by

accelerating the movement of glucose out of the blood into cells, which increases glucose metabolism by cells.

Diabetes mellitus- Type 1 results from hyposecretion of insulin

- Type 2 result from target cell insensitivity to insulin

- Glucose cannot enter cells and thus blood glucose levels rise, producing glycosuria (glucose in the urine)

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Female Sex Glands The ovaries contain two structures that secrete hormones :

- The ovarian follicles- And The corpus luteum

Granulosa cells ; produces estradiol, first half of cycle

Corpus luteum ; follicle after ovulation, produce estradiol and progesterone

Effects of estrogen Development and maturation of breasts and external genitals

Development of adult female body contours

Initiation of menstrual cycle

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Male Sex Gland

The interstitial cells of testes secrete the male hormone testosterone.

Effect of testosterone (Masculinizing hormone)

- Maturation of external genitals- Beard growth- Voice change at puberty- Development of musculature and body contours

typical of the male

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Thymus

Name of Hormone – Thymosin

Function of Hormone – plays an important role in the development and function of the body’s immune system.

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Endocrine Function of Other Organs Heart –

○ ANP (atrial natriuretic peptide) released with an increasing BP

○ Decrease Na+ and H2O loss by kidneys cause low blood volume and low BP

Skin – Helps produce vitamin D3

Liver – ○ 15% of erythropoietin secrete (stimulates bone marrow)○ Angiotensinogen ( a prohormone) – precursor of

angiotensin II causes increase BP○ Converts D3 to calcidiol

○ Hepcidin – promotes intestinal absorption of iron

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Endocrine Function of Other Organs Kidneys –

○ Erythropoietin – stimulate production of RBC’s○ Converts angiotensinogen to angiotensin I○ Converts calcidiol to calcitriol ( activate from vitamin D)

Stomach and small intestine – Coordinate digestive motility and secretion

Placenta – ○ Secretes estrogen, progesterone and others○ Regulate pregnancy, stimulate development of fetus

and mammary gland.

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Action of ADH : Water retention

ADH has two actions, one on the kidney and the other on vascular smooth muscle. These actions are mediated by different receptors, different intra cellular mechanism, and different second messengers

ADH increase in water permeability○ The major action of ADH is to increase the water permeability of cells in the

kidney distal tubule and collection duct.

○ The receptor for ADH on kidney cells is V2 receptor, which is coupled to adenyl cyclase via G protein

○ The 2nd messenger is cAMP, which via phosphorylation steps, directs the insertion of water channels, aquaporin 2, into the kidney cell membrane

○ The increased water permeability of the cells allows more water to be reabsorbed by the collecting ducts ( water moves from urine to blood) and makes the urine more concentrated

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ADH and Contraction of vascular smooth muscle

The 2nd action of ADH is to cause contraction of vascular smooth muscle

The receptor for ADH on vascular smooth muscle is a V1 receptor, which is coupled to phospholipase C via a G protein

The 2nd messenger for this action is an IP2/Ca cascade which produces contraction of vascular smooth muscle, contraction of arterioles, and increased total peripheral resistance

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Pathways involved in control of ADH

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ADH Disorders

Hyposecretion due to damaged of hypothalamic nucleus or neurohypophysis – diabetes insipidus – excessive urine production (polyuria) and thirst

Hypersecretion – SIADH ( Syndrome of inappropriate ADH secretion)

○ Water retention, cerebral edema, headache, weight gain, hypo- osmolarity

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Questions The ____ gland located in front of neck and secretes a hormone that

aids in the regulation of the body’s metabolic rate.

The _____ gland the smallest of the endocrine glands, secrete a hormone which regulates the concentration of calcium and phosphorus in the blood.

The ______ secretes glucocorticoids which help the body meet condition of stress.

A small cone shaped gland, the ______ gland is located inside the cranial cavity, secretes the hormone melatonin which seems to inhibit reprodutive activities.

The alpha cells of the ______ secrete glucagon, a hormone produced when the body’s blood sugar gets too low.

________ cells secrete insulin which causes a decrease in blood sugar by increasing the body’s ability to take up and use sugar.

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Questions The hormone somatostatin is produced by the ______

A principle effect of the _______ gland is to regulate the body’s metabolic rate.

______ is the hormone which releases milk formed by the glandular cells of the nursing female.

The adrenocorticotropic hormone (ACTH) has the primary action of _________________________________

The _________ hormone is secreted by the anterior lobe of the pituitary gland and stimulate the normal growth cycle of the ovarian follicle in females

____________ hormone is secreted by the posterior lobe of the pituitary gland. This hormone makes the collecting duct of the kidney permeable to water and allows concentration of water.

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Questions The hormone which promotes the maturation of the ovarian follicle as well as

the secretion of progesterone is the _____ hormone.

The hormone which works with estrogen to regulate menstruation is _______

The hormone responsible for the secondary sex characteristic of voice pitch, broad pelvis, and hair pattern in women is _____

The hormone responsible for secondary sex characteristic for men is ______

The gland responsible for animal coming into heat is the ___________ gland.

The mineralocorticoid help maintain _______ balance and ______ balance.

The catecholamine hormones epinephrine and norepinephrine are commonly known as the _________ hormones because they give body extra energy in stressful situation.

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Answers Thyroid Parathyroid Adrenal cortex Pineal Pancreas Beta cells Delta cells Thyroid Oxytocin Promoting and maintaining

normal growth and development of the adrenal cortex

•Follicle stimulating•Antidiuretic•Lutenizing•Progesterone•Estrogen•Testosterone•Pineal•Electrolyte fluid•Fight or flight

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