Endocrine System

• Endocrinology - Study of hormones, their functions, their mechanisms of action, and their disorders of function.

• Hormone (Greek word meaning "to arouse to activity," "to excite," or "to set into motion") - Chemical substance secreted into the blood by an endocrine gland(s) and carried by the blood to target cells that respond to the hormone by changing their metabolism.

• Endocrine glands are ductless glands that have a rich blood supply.

• Target organ - Organ specifically affected by the action of a hormone. The target organ must have specific receptor proteins for hormones.

• Activation of protein hormones

• Often derived from a larger, less active "precursor" molecule (preprohormone) that is progressively cleaved into a prohormone and then a hormone. Occurs in endocrine organ producing the preprohormone or in the target organ to produce the active hormone.

• Inactivation of hormones occurs in the liver primarily, but the kidneys can also inactivate a hormone in order to make it more soluble for excretion in the urine.

• Ways to regulate hormones

• Alter rate of synthesis or secretion of hormone

• Alter receptor number (up or down regulation)

• Alter rate of destruction or excretion of hormone

• Many hormones are secreted on a rhythmic basis with release patterns of varying lengths.  For example, hormones with release patterns every 24 hours have a rhythm that is circadian.

• Most hormones are associated with some endocrine abnormality.

• Negative feedback - A response mechanism in which a change in the internal environment triggers a response that serves to counteract that change.  Most hormones are regulated in this manner.

Feedback Loops (long loop and short loop) 

Gland A Hormone 1 Gland B Hormone 2 Gland C Hormone  3

 

• Hormone Interactions

• Synergistic - 2 or more hormones work together to produce a particular result that is greater than each individual hormone alone.

• Examples:

• E₂, cortisol, PRL, and OT on mammary gland milk protein development and secretion.

• Epinephrine and norepinephrine on heart rate and/or force of contraction.

• Permissive - Presence of 1 hormone in adequate amounts enhances the responsiveness of a target organ to a second hormone.

• Example:

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

• PTH and  Vitamin D₃ on intestinal absorption of calcium

• Antagonistic - Actions of 1 hormone inhibit the effects of another.

• Examples:

• Insulin and glucagon on adipose tissue.

• Estrogen inhibits PRL during pregnancy.

Pituitary Gland (Hypophysis)

• Adenohypophysis (Anterior pituitary gland - glandular)

• Produces and secretes its own hormones (collectively called trophic hormones which act upon other endocrine glands).

• Controlled by the hypothalamus via releasing or release-inhibiting hormones.

• Hypothalamic hormones reach anterior pituitary via the hypothalamo-hypophyseal portal system.

• Capillary bed Portal Venule Capillary bed Vein

• Neurohypophysis (Posterior pituitary gland - neural)

• Secretes hormones that are produced by the hypothalamus and stored in the posterior pituitary.

• Hormones secreted by the anterior pituitary:                           (Note: The plus sign (+) means stimulates in these notes.)

• Growth hormone (GH): + protein synthesis and growth, + fat breakdown, and increases blood glucose levels

• Disorders: Dwarfism, gigantism, acromegaly

 (see Clinical box on pg. 321 for details)

• Growth-promoting effects of GH occur via insulin-like growth factors (IGF's) = somatomedins.  See Fig. 19.17 on pg. 663.

• Thyroid-stimulating hormone (TSH): + thyroid gland to secrete the hormones T₄ and T₃

• Adrenocorticotropic hormone (ACTH): + adrenal cortex to secrete glucocorticoids

• Follicle-stimulating hormone (FSH): + sperm production and + growth of ovarian follicles

• Luteinizing hormone (LH): + ovulation, estrogen and progesterone secretion, corpus luteum formation, and testosterone secretion

• Together, LH and FSH are called gonadotropins.

• Prolactin (PRL): + milk production in females.  Function in males is less clear.  See pg. 720.

• Hormones secreted by the posterior pituitary.

• Antidiuretic hormone (ADH) = Vasopressin = Arginine vasopressin (AVP):

+ kidneys to retain water which concentrates the urine and decreases its volume; + an increase in blood pressure.

• Disorder: Diabetes insipidus - Due to: 1) a deficiency of ADH or 2) a failure to respond to any ADH produced.

• Oxytocin (OT):  + uterine contractions and + mammary gland alveoli and duct contractions leading to milk let-down (milk ejection).

• Function of OT in males is less clear.

• Control of OT:  + of sensory neurons in nipples, stimulation of cervix by infant in birth canal, conditioning

• Can be used to induce labor in pregnant women.

• Intermediate lobe

• Poorly defined to absent in adult humans; present in fetus and other animals.

• Secretes melanocyte stimulating hormone (MSH) - Causes skin darkening in lower vertebrates. May cause skin darkening in humans if abnormally produced in sufficient quantities.

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• Hypothalamic control of anterior pituitary occurs via releasing and release-inhibiting hormones (See Table 11.7 on Pg. 323)

• GHRH, somatostatin (GHIH), TRH, CRH, GnRH, PIH (dopamine), and PRH - See text for the names of each hormone.

• Axis - Relationship between hypothalamus, pituitary, and target organ.

                     Examples: Hypothalamic-pituitary-gonadal (HPG) axis; hypothalamic-pituitary-thyroidal (HPT) axis

• Adrenal Gland

• Cortex - Secretes corticosteroids or corticoids.

• Zona glomerulosa (ZG) - Secretes mineralocorticoids (i.e., aldosterone) which regulate Na⁺ reabsorption and K⁺ excretion.

• Zona fasiculata (ZF) - Secretes glucocorticoids (i.e., cortisol) which  increases blood glucose, amino acids, and fatty acids, has anti-inflammatory and immunosuppressive effects, and provides adaptation to stress.

• Zona reticularis (ZR) - Secretes primarily sex steroids (weak androgens).

• Medulla (innervated by preganglionic sympathetic neurons).

• Secretes epinephrine and norepinephrine (4:1), particularly when the body is under stress. Prepares body for fight-or-flight response by mobilizing energy reserves (increases blood glucose and fatty acids).

Disorders: Cushing's syndrome and Addison's disease (see Clinical box on pg. 327)

• Thyroid Gland: Contains follicles that produce thyroid hormones.

Secretes thyroxine (T₄) and triiodothyronine (T₃). T₃ is more active than T₄.  + basal metabolic rate (BMR), + heat production, + thyroid gland growth, and is required for normal CNS development.

• Hypothyroidism - Deficiency of T₄.

• Cretinism - Hypothyroidism during prenatal and early postnatal development.

• Hyperthyroidism (Graves’ Disease) - Autoimmune condition that results in increased secretion of T₄.

• Goiter - Enlargement of the thyroid gland.  Different mechanisms can cause goiter.

• Secretes calcitonin (a hypocalcemic hormone)

• Produced by parafollicular cells.

• Decreases blood Ca²⁺ by: 1) promoting deposition in bone and 2) increasing renal excretion.

• Parathyroid Gland

• Located on back surface of thyroid gland.

• Secretes parathyroid hormone (PTH) = parathormone (a hypercalcemic hormone)

• Increases blood Ca²⁺ and decreases blood phosphate by: 1) + retention by kidneys, 2) + absorption by small intestine via vitamin D₃, and 3) + bone breakdown.

• Endocrine Pancreas

• Cells are found within the islets of Langerhans.

• Beta cells - Secrete insulin - Decreases blood glucose by + glucose uptake into cells, + fat synthesis, and + protein synthesis.

• Diabetes mellitus - Results from insulin deficiency (Type I) or decreased tissue sensitivity to the effects of insulin (Type II).  Symptoms: Increased blood sugar, increased urinary glucose excretion, increased urinary excretion, increased thirst, increased eating, increased ketones excreted in urine.

• Alpha cells - Secrete glucagon - Increases blood glucose in response to hypoglycemia (e.g, during fasting).  Opposite effects to those of insulin.

• Pineal gland

• Secretes melatonin.

• Produced at night and inhibited by light.

• Inhibits reproductive function in many species by inhibiting HPG axis.

• Stimulated by activity of the SCN.

• Affects biological rhythmicity.

• Pattern of secretion is altered by shift work and travel across several time zones.

• Gastrointestinal System

• Stomach and small intestine secrete hormones that act on the GI tract itself and on the pancreas and gallbladder.  (We will study these hormones if we get to the GI system later in the semester.) 

• Kidney

• Secretes erythropoietin: + RBC production in response to decreased blood oxygen levels. This can occur during anemia or when remaining at a higher altitude for a prolonged period, for example.

• Heart (atria)

• Secretes atrial natriuretic peptide (ANP) which + Na⁺ and water excretion by the kidneys.

• Skin

• Produces Vitamin D₃ which, after further conversion by the liver and kidneys, directly stimulates Ca²⁺ retention by the small intestine.

• Adipose tissue

• Secretes leptin which monitors fat stores and reduces appetite and food intake.

• Testes

• Secrete testosterone (an androgen) from the Leydig cells.  + reproductive development (primary sex characteristics), secondary sex characteristics, sex drive (libido).

• Ovaries

• Secrete estrogen and progesterone from follicles.

• + reproductive development (primary sex characteristics), secondary sex characteristics, sex drive, prepares uterus for pregnancy and maintains uterus during pregnancy, prepares mammary gland for milk production.

• Placenta (site of communication between mother and fetus)

• Secretes: 

  Estrogen and Progesterone

  Human Chorionic Gonadotropin (hCG): Helps to maintain corpus luteum and to prevent menstruation.

  Human Placental Lactogen (hPL): + growth and development of the mammary gland for postpartum lactation.

  Relaxin: Softens cervix and connective tissue (pubic symphysis) between pelvic bones.  The ovary also produces relaxin.  It  may not be significantly involved in human childbirth.

   

Mechanisms of Hormone Action

• Location of hormone's receptor proteins in the target cells depends on the chemical classification of the hormone.

• Steroids and T₄ - Receptor proteins w/in the cytoplasm or nucleus (nuclear hormone receptors) of target cells.

• Proteins - Receptors in the target cell membrane.

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• Steroid Hormones (H)

• H. transported in blood bound to carrier protein.

• H. dissociates from carrier and diffuses through cell membrane into interior of cell.

• H. binds to a cytoplasmic or nuclear receptor (R) protein.

• H-R complex translocates (if not already in nucleus) to nucleus and binds to its hormone response element (HRE) on the DNA.

• Gene activation      mRNA synthesis      protein synthesis      hormone response

• Thyroid Hormones

• T₄ transported in blood bound to a carrier protein = thyroxine binding globulin (TBG).

• T₄ dissociates from carrier and diffuses through cell membrane into interior of cell.

• T₄ is enzymatically converted to T₃ by deiodinase.

• T₃ binds to a nuclear receptor (R) protein.

• T₃-R complex binds to its hormone response element on the DNA.

• Gene activation      mRNA synthesis      protein synthesis      hormone response

• Peptides (cannot pass through the lipid barrier of the cell membrane. Other molecules mediate the actions of the hormones).

• H. binds to receptors (R) on the outer surface of target cell membranes (H = "first messenger").

• H-R complex activates G protein which stimulates activation of adenylate cyclase (AC).

• AC catalyzes the conversion of ATP to cyclic adenosine monophosphate (cAMP; a 2^nd messenger).

• cAMP activates inactive protein kinases (PK) by removing the inhibitory subunit.

• Activated PK's transfer phosphate groups to other enzymes, thereby activating or inactivating them.

• Altered enzyme activity mediates the target cell's response to the hormone.

• cAMP is deactivated by phosphodiesterase (PDE).

• There are numerous examples of other 2nd messengers. cAMP is not the only one.

 

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