Chapter 11 Endocrine Glands. Copyright © The McGraw-Hill Companies, Inc. Permission required for...

Chapter 11

Endocrine Glands

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Hormones

Regulatory molecules secreted into the blood or lymph by endocrine glands.

Lack ducts.

Carry hormone to target tissue where it produces its effects.


Chemical Classification of Hormones

Amines Polypeptides Glycoproteins Steroids


Amines

Hormones derived from tyrosine and tryptophan.

Include hormones secreted by adrenal medulla, thyroid, and pineal glands.


Polypeptides

Chains of amino acids (< 100 amino acids in length). ADH Insulin


Glycoproteins

Long polypeptides (>100) bound to one or more carbohydrate (CHO) groups. FSH LH


Steroids Lipids derived

from cholesterol. Are lipophilic

hormones. Testosterone Estradiol Cortisol Progesterone


Thyroid Hormones

Tyrosine derivatives bound together.

Contain 4 iodine atoms (T4).

Contain 3 iodine atoms (T3).

Small, non-polar molecules.

Soluble in plasma membranes.


Hormone Precursors

Prohormone: Precursor is a longer chained

chemical that is cut and spliced to make the hormone.

Preprohormone: Prohormone derived from larger

precursor molecule. Prehormone:

Molecules secreted by endocrine glands that are inactive until changed to hormones by target cells.


Synergism: Two hormones work together to produce

a result. Additive:

Each hormone separately produces response, together at same concentrations stimulate even greater effect.

Epinephrine and norepinephrine.

Complementary: Each hormone stimulates different step in the

process. FSH and testosterone.

Hormonal Interactions



Permissive effects: Hormone enhances the

responsiveness of a target organ to second hormone.

Increases the activity of a second hormone.

Prior exposure of uterus to estrogen induces formation of receptors for progesterone.



Antagonistic effects: Action of one hormone antagonizes

the effects of another. Insulin and glucagon.


Effects of Hormone Concentration

Concentration of hormones in blood reflects the rate of secretion.

Half-life: Time required for the plasma

concentration is reduced to ½ reference level.

Physiological range of concentration produces normal tissue response.



Varying hormone concentration within normal, physiological range can affect the responsiveness of target cells.

Priming effects (upregulation) Increase number of receptors formed

on target cells. Greater response by the target cell.



Desensitization (downregulation): Decrease in number of receptors on

target cells. Produces less of a target cell

response. Insulin in adipose cells.

Pulsatile secretion may prevent downregulation. GnRH and LH.


Mechanisms of Hormone Action

Hormones of same chemical class have similar mechanisms of action. Location of cellular receptor proteins.

Target cell must have specific receptors for that hormone (specificity).

Hormones bind to receptors with high bond strength (affinity).

Low capacity of receptors (saturation).

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.Hormones That Bind to Nuclear Receptor Proteins

Lipophilic steroid and thyroid hormones bound to plasma carrier proteins.

Hormones dissociate from carrier proteins to pass through lipid component of the target cell membrane.

Receptors for the lipophilic hormones are known as nuclear hormone receptors.


Nuclear Hormone Receptors

Function within cell to activate genetic transcription.

mRNA directs synthesis of specific enzyme proteins that change metabolism.

Receptor must be activated by binding to hormone before binding to specific region of DNA called HRE (hormone responsive element). Located adjacent to gene that will be

transcribed.


Mechanisms of Steroid Hormone Action

Steroid receptors located in cytoplasm.

Bind to steroid hormone.

Translocates to nucleus.

DNA-binding domain binds to specific HRE of the DNA.

Dimerization occurs. Stimulates

transcription.


Mechanism of Thyroid Hormone Action

Receptor proteins located in nucleus.

T3 binds to ligand-binding domain.

DNA-binding domain can then bind to the half-site of the HRE.

Other half-site is vitamin A derivative 9-cis-retinoic acid.

Two partners can bind to the DNA to activate HRE.


Hormones That Use 2nd Messengers

Cannot pass through plasma membrane. Catecholamines, polypeptides, and

glycoproteins bind to receptor proteins on the target cell membrane.

Actions are mediated by 2nd messengers (signal-transduction mechanisms). Extracellular hormones are transduced

into intracellular second messengers.


Hormones That Use 2nd Messengers

3 classes of 2nd messenger systems: Adenylate cyclase. Phospholipase C. Tyrosine kinase.


Hormone binds to receptor protein. Dissociation of a subunit of G-

protein. G-protein binds and activates

adenylate cyclase. ATP cAMP + PPi cAMP attaches to inhibitory subunit

of protein kinase.

Adenylate Cyclase-cAMP


Activates protein kinase. Phosphorylates enzymes within the cell

to produce hormone’s effects. Modulates activity of enzymes present

in the cell. Alters metabolism of the cell. cAMP inactivated by phosphodiesterase.

Hydrolyzes cAMP to inactive fragments.

Adenylate Cyclase-cAMP


Binding of epinephrine to alpha-adrenergic receptor activates a G-protein, (phospholipase C).

Phospholipase C splits phospholipid into IP3 and DAG.

Both derivatives serve as second messengers.

Phospholipase-C-Ca++


IP3 diffuses through cytoplasm to ER. Binding of IP3 to receptor protein in ER

causes Ca++ channels to open. Ca++ diffuses into the cytoplasm. Ca++ binds to calmodulin. Calmodulin activates specific protein

kinase enzymes. Alters the metabolism of the cell,

producing the hormone’s effects.

Phospholipase-C-Ca++


Receptor protein on cell membrane is tyrosine kinase.

Insulin receptor consists of 2 units that dimerize when they bind with insulin.

Insulin binds to ligand–binding site, activating enzymatic site.

Autophosphorylation occurs, increasing tyrosine kinase.

Activates signaling molecules, altering the metabolism of the cell.

Tyrosine Kinase


Anterior and posterior pituitary glands.


Also called the neurohypophysis. Formed by downgrowth of the

brain during fetal development. Is in contact with the infundibulum. Nerve fibers extend through the

infundibulum.

Posterior Pituitary


Hypothalamic Control of Posterior Pituitary

Hypothalamus produces:

ADH: supraoptic nuclei. Oxytocin: paraventricular

nuclei. Hormones transported

along the hypothalamo-hypophyseal tract.

Stored in posterior pituitary.

Release controlled by neuroendocrine reflexes.


Master gland (also called adenohypophysis).

Derived from a pouch of epithelial tissue that migrates upward from the mouth.

Consists of 2 parts: Pars distalis: anterior pituitary. Pars tuberalis: thin extension in

contact with the infundibulum.

Anterior Pituitary


Trophic effects: Health of the target glands,

depends upon stimulation by anterior pituitary for growth.

High plasma hormone concentration causes target organ to hypertrophy.

Low plasma hormone concentration causes target organ to atrophy.

Anterior Pituitary


Hormonal control rather than neural. Hypothalamus synthesizes releasing

hormones and inhibiting hormones. Hormones are transported to axon

endings of median eminence. Delivers blood and hormones to anterior

pituitary via portal system.

Hypothalamic Control of the Anterior Pituitary


Hypothalamic Control of the Anterior Pituitary

Hormones secreted into the hypothalamo-hypophyseal portal system regulate the secretions of the anterior pituitary.


Anterior pituitary and hypothalamic secretions are controlled by the target organs they regulate.

Negative feedback inhibition by target gland hormones.

Feedback Control of the Anterior Pituitary


Feedback Control of the Anterior Pituitary

Negative feedback at 2 levels: The target gland hormone can act on

the hypothalamus and inhibit releasing hormones.

The target gland hormone can act on the anterior pituitary and inhibit response to the releasing hormone.


Adrenal Glands

Paired organs that cap the kidneys. Each gland consists of an outer cortex

and inner medulla. Adrenal medulla:

Derived from embryonic neural crest ectoderm (sympathetic ganglia).

Synthesizes and secretes: Catecholamines (mainly epinephrine but some

norepinephrine).


Adrenal Glands

Adrenal cortex: Does not receive neural innervation. Must be stimulated hormonally. Consists of 3 zones:

Zona glomerulosa: Aldosterone: regulate Na+ and K+ balance.

Zona fasciculata: Cortisol: regulate glucose metabolism.

Zona reticularis: Androstenedione and DHEA: supplement sex

steroids.


Adrenal Medulla

Innervated by sympathetic nerve fibers. Increase respiratory rate. Increase heart rate, cardiac output;

and vasoconstrict blood vessels, thus increasing venous return.

Stimulate glycogenolysis. Stimulate lipolysis.


General Adaptation Syndrome (GAS)

Stress stimulates pituitary-adrenal axis

Alarm phase: Adrenal glands activated.

Stage of resistance: Stage of readjustment.

Stage of exhaustion: Sickness and/or death if readjustment

does not occur.


Thyroid Hormones

Thyroid gland located just below the larynx.

Thyroid is the largest of the pure endocrine glands.

Follicular cells secrete thyroxine. Parafollicular cells secrete

calcitonin.


Production of Thyroid Hormones

I- (iodide) actively transported into the follicle and secreted into the colloid.

Oxidized to (Io) iodine. Iodine attached to tyrosine.

Attachment of 1 iodine produces monoiodotyrosine (MIT).

Attachment of 2 iodines produces diiodotyrosine (DIT).

MIT and DIT or 2 DIT molecules coupled.


Production of Thyroid Hormones

T3 and T4 produced. TSH stimulates pinocytosis into the

follicular cell. Enzymes hydrolyze to T3 and T4 from

thyroglobulin. Attached to thyroid-binding protein

and released into blood.


T3 Effects

Stimulates cellular respiration by: Production of uncoupling proteins. Stimulate active transport Na+/ K+

pumps. Lower cellular [ATP].

Increases metabolic heat. Increases metabolic rate.

Stimulates increased consumption of glucose, fatty acids and other molecules.


Parathyroid Hormone Parathyroid glands embedded in

the lateral lobes of the thyroid gland.

Only hormone secreted by the parathyroid glands.

Single most important hormone in the control of plasma Ca++ concentration.

Stimulated by decreased plasma Ca++ concentration.


Pancreas

Endocrine portion consists of islets of Langerhans.

Alpha cells secrete glucagon. Stimulus is decrease in plasma glucose

concentrations. Stimulates lipolysis.

Beta cells secrete insulin. Stimulus is increase in plasma glucose

concentrations. Promotes entry of glucose into cells.


Penal Gland

Melatonin: Production stimulated by the

suparchiasmatic nucleus (SCN) in hypothalamus.

SCN is primary center for circadian rhythms.

May inhibit GnRH.


Thymus

Site of production of T cells (thymus-dependent cells), which are lymphocytes.


Gonads and Placenta

Gonads (testes and ovaries): Secrete sex hormones.

Testosterone. Estradiol. Progesterone.

Placenta: Secretes large amounts of estrogen

and progesterone.


Autocrine and Paracrine Regulation

Autocrine: Produced and act within the

same tissue of an organ. Paracrine:

Are produced within one tissue and regulate a different tissue of the same organ.


Prostaglandins

Most diverse group of autocrine regulators.

Produced in almost every organ. Wide variety of functions.

Immune system: Promote inflammatory process.

Reproductive system: Play role in ovulation.

Digestive system: Inhibit gastric secretion.


Prostaglandins

Respiratory system: May bronchoconstrict or bronchodilate.

Circulatory system: Vasoconstrictors or vasodilators.

Urinary system: Vasodilation.

Chapter 11 Endocrine Glands. Copyright © The McGraw-Hill Companies, Inc. Permission required for...

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