The Endocrine Glands: Secretion/action Of Hormones

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Endocrine Glands

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Are ductless and secrete hormones into bloodstream
Hormones travel to target cells that contain receptor proteins for it
Neurohormones are secreted into blood by specialized neurons
Hormones affect metabolism of targets

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Primary Endocrine Organs (7)

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Hypothalamus and pituitary gland
Pineal gland
Thyroid gland and parathyroid glands
Thymus
Adrenal glands
Pancreas
Gonads

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Chemical Classification of Hormones (4)

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Amine hormones are derived from tyrosine or tryptophan. Include Norepinephrine, Epinephrine, thyroxine, melatonin.

Polypeptide and protein hormones are chains of amino acids. These include ADH, GH, insulin, oxytocin, glucagon, ACTH, PTH.

Glycoproteins include LH, FSH, TSH.

Steroids are lipids derived from cholesterol. These include testosterone, estrogen, progesterone, alsoterone and cortisol.

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What does it mean when 2 hormones are synergistic?

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2 hormones are synergistic if work together to produce a larger effect together than individual effects added together.

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What does it mean when a hormone has a permissive effect?

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A hormone has permissive effect if it enhances responsiveness of a target organ to 2nd hormone.

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T/F, Normal tissue responses are produced only when hormones are in physiological range

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True

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3 things that target cells show for a hormone

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specificity, high affinity, and low capacity

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Describe genomic action

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Lipophilic hormones have receptors in target's cytoplasm and/or nucleus because can diffuse thru plasma membrane
Their target is the nucleus where they affect transcription
Called genomic action and takes at least 30 mins

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Describe nongenomic action

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Receptors for hydrophilic hormones are on surface of target cell
These act through 2nd messengers; effects are quick
Some steroids also act on cell surface receptors

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How Do Lipid Hormones Bind to Nuclear Receptor Proteins?

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Lipid hormones travel in blood attached to carrier proteins.
They dissociate from carriers to pass thru plasma membrane of target cell.
Receptors are called nuclear hormone receptors

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Nuclear Hormone Receptors

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Serve as transcription factors when bound to hormone ligands
Activate transcription
Constitute a "superfamily" composed of steroid family and thyroid hormone family (which includes vitamin D and retinoic acid)

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Mechanisms of Steroid Hormones

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Hormone Response Element consists of 2 half-sites. 2 ligand-bound receptors have to bind to each HRE (dimerization)
This stimulates transcription of target gene.

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Mechanism of Thyroid Hormone Action

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Thyroid secretes 90% T4 (thyroxine) and 10% T3
99.96% of T4 in blood is bound to carrier protein (thyroid binding globulin - TBG)
Only free thyroxine and T3 can enter cells
Protein bound thyroxine serves as a reservoir
T4 converted to T3 inside target cell
T3 binds to receptor protein located in nucleus
The receptor for T3:
T3 and receptor bind to 1 half-site
Other half-site binds retinoic acid
Two partners form heterodimer that activates HRE
Stimulates transcription of target gene

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Hormones That Use 2nd Messengers

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Water soluble hormones use cell surface receptors because cannot pass through plasma membrane
Actions are mediated by 2nd messengers
Hormone is extracellular signal; 2nd messenger carries signal from receptor to inside of cell

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Adenylate Cyclase-cAMP Mechanism

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cAMP mediates effects of many polypeptide and glycoprotein hormones
Hormone binds to receptor causing dissociation of a G-protein subunit
G-protein subunit binds to and activates adenylate cyclase
Which converts ATP into cAMP
cAMP attaches to inhibitory subunit of protein kinase
Inhibitory subunit dissociates, activating protein kinase
Which phosphorylates enzymes that produce hormone’s effects
cAMP inactivated by phosphodiesterase

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Tyrosine Kinase 2nd Messenger System

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Is used by insulin and many growth factors to cause cellular effects
Surface receptor is tyrosine kinase
Consists of 2 units that form active dimer when insulin binds
Activated tyrosine kinase phosphorylates signaling molecules that induce hormone/growth factor effects

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Insulin Action

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Insulin stimulates glucose uptake by means of GLUT 4 carrier proteins
2nd messengers cause vesicles containing GLUT4 transporters to be inserted into plasma membrane

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where is the pituitary gland located?

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beneath hypothalamus at base of forebrain

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Distinguish between the functions of the anterior and posterior portions of the pituitary gland.

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Anterior produces own hormones
Controlled by hypothalamus
Posterior stores and releases hormones made in hypothalamus (vasopressin and oxytocin)

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trophic hormones - general definition

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hormones secreted from the anterior pituitary that maintain size of targets

High blood levels cause target to hypertrophy

Low levels cause atrophy

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name the six trophic hormones secreted by the anterior pitutary

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Growth hormone (GH) promotes growth, protein synthesis, and movement of amino acids into cells
Thyroid stimulating hormone (TSH) stimulates thyroid to produce and secrete T4 and T3
Adrenocorticotrophic hormone (ACTH) stimulates adrenal cortex to secrete cortisol, aldosterone
Follicle stimulating hormone (FSH) stimulates growth of ovarian follicles and sperm production
Luteinizing hormone (LH) causes ovulation and secretion of testosterone in testes
Prolactin (PRL) stimulates milk production by mammary glands

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Growth hormone (GH)

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promotes growth, protein synthesis, and movement of amino acids into cells

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Thyroid stimulating hormone (TSH)

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stimulates thyroid to produce and secrete T4 and T3

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Adrenocorticotrophic hormone (ACTH)

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stimulates adrenal cortex to secrete cortisol, aldosterone

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Follicle stimulating hormone (FSH)

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stimulates growth of ovarian follicles and sperm production

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Luteinizing hormone (LH)

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causes ovulation and secretion of testosterone in testes

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Prolactin (PRL)

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stimulates milk production by mammary glands

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what controls Release of Anterior Pituitary hormones (2)

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hypothalamic releasing and inhibiting factors

by feedback from levels of target gland hormones

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Releasing and inhibiting hormones from hypothalamus

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Releasing and inhibiting hormones from hypothalamus are released from axon endings into capillary bed
Carried by hypothalamo-hypophyseal portal system directly to another capillary bed in A. Pit.
Diffuse into A. Pit. and regulate secretion of its hormones

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Feedback Control of Anterior Pituitary

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The hypothalamic-pituitary-gonad axis (control system)
Involves short feedback loop in which retrograde flow of blood and hormones from A. Pit. to hypothalamus inhibits secretion of releasing hormone
Involves negative feedback of target gland hormones
And during menstrual cycle, estrogen stimulates “LH surge” by positive feedback

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Higher Brain Function and Anterior Pituitary Secretion

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Hypothalamus receives input from higher brain centers that can affect A. Pit. secretion
e.g. emotional states and psychological stress can affect circadian rhythms, menstrual cycle, and adrenal hormones

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2 hormones produced in hypothalamus; Stored and released Posterior Pituitary

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Antidiuretic hormone (ADH/vasopressin) which promotes H2O conservation by kidneys
Oxytocin which stimulates contractions of uterus during parturition
And contractions of mammary gland alveoli for milk-ejection reflex

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Hypothalamic Control of Posterior Pituitary

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Supraoptic nuclei of hypothalamus produce ADH
Paraventricular nuclei produce oxytocin
Both transported along hypothalamo-hypophyseal tract to posterior pituitary
Release controlled in hypothalamus by neuroendocrine reflexes

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Adrenal Glands

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Sit on top of kidneys
Each consists of outer cortex and inner medulla
which arise differently during development

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Differentiate between the medulla and cortex of the adrenal glands

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Medulla synthesizes and secretes 80% Epinephrine and 20% Norepinephrine
Controlled by sympathetic division of ANS
Cortex is controlled by ACTH and secretes:
Cortisol which inhibits glucose utilization and stimulates gluconeogenesis
Aldosterone which stimulate kidneys to reabsorb Na+ and secrete K+
And some supplementary sex steroids

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Hormonal effects of Epinephrine last 10X longer than Norepinephrine
Innervated by preganglionic Sympathetic fibers
Activated during "fight or flight" response
Causes:
Increased respiratory rate
Increased HR and cardiac output
General vasoconstriction which increases venous return
Glycogenolysis and lipolysis

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Adrenal Medulla

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Stress and the Adrenal Gland

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Stress induces a non-specific response called general adaptation syndrome (GAS)
Causes ACTH and cortisol release

Chronic stress can induce high levels of cortisol that cause a number of negative effects:
atrophy of hippocampus (involved in memory)
reduced sensitivity of tissues to insulin (insulin resistance)
inhibition of vagus nerve activity
suppression of growth hormone, thyroid hormone, and gonadotropins

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Is located just below the larynx
Secretes T4 and T3 which set BMR and are needed for growth, development
A scan of the thyroid 24 hrs. after intake of radioactive iodine (b)

Consists of microscopic thyroid follicles
Outer layer is follicle cells that synthesize T4
Interior filled with colloid, a protein-rich fluid

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Thyroid Gland

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Production of Thyroid Hormones

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Iodide (I-) in blood is actively transported into follicles and secreted into colloid
Where it is oxidized to iodine (I2) and attached to tyrosines of thyroglobulin
A large storage molecule for T4 and T3
TSH stimulates hydrolysis of T4 and T3s from thyroglobulin and then secretion

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Diseases of the Thyroid - Goiter

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In absence of sufficient dietary iodide, T4 and T3 cannot be made and levels are low
Low T4 and T3 don’t provide negative feedback and TSH levels go up
Because TSH is a trophic hormone, thyroid gland grows
Resulting in a goiter

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Diseases of the Thyroid - Hypothyroidism

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People with inadequate T4 and T3 levels are hypothyroid
Have low BMR, weight gain, lethargy, cold intolerance
And myxedema = puffy face, hands, feet
During fetal development hypothyroidism can cause severe mental retardation

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Parathyroid Glands

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Are 4 glands embedded in lateral lobes of post. side of thyroid gland
Secrete Parathyroid hormone (PTH)
Most important hormone for control of blood Ca2+ levels

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Parathyroid Hormone

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Release stimulated by decreased blood Ca2+
Acts on bones, kidney, and intestines to increase blood Ca2+ levels

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Islets of Langerhans

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scattered clusters of endocrine cells in pancreas
Contain alpha and beta cells

Alpha cells secrete glucagon in response to low blood glucose
Stimulates glycogenolysis and lipolysis
Increases blood glucose

Beta cells secrete insulin in response to low blood glucose
Promotes entry of glucose into cells
And conversion of glucose into glycogen and fat
Decreases blood glucose

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Is located in basal forebrain near thalamus
Secretes melatonin in response to activity of suprachiasmatic nucleus (SCN) of hypothalamus

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Pineal Gland

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SCN is primary timing center for circadian rhythms
Reset by daily light/dark changes
Melatonin is involved in aligning physiology with sleep/wake cycle and seasons
Secreted at night and is inhibited by light
Implicated in jet-lag

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Pineal Gland

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GI organs which produce hormones

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Stomach
Small intestine
Act on GI tract itself, gallbladder, and pancreas
Act in convert with ANS to coordinate regions of GI tract and pancreatic juice and bile

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Sex and Reproductive Hormones

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Gonads (testes and ovaries) secrete steroid hormones testosterone, estrogen, and progesterone
Placenta secretes estrogen, progesterone, hCG, and somatomammotropin

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Autocrine and Paracrine Regulation

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Autocrine regulators are produced and act within same tissue of an organ
All autocrines control gene expression in target cells
Paracrine regulators are produced within one tissue and act on different tissue in same organ.