Chapter 17

The Endocrine SystemFunctions

◦ Differentiation of reproductive and CNS in fetus

◦ Stimulation of growth and development

◦ Coordination of the male and female reproductive system

◦ Maintenance of internal environment

◦ Adaptation to emergency demands of the body

HormonesGeneral characteristics

◦ Specific rates and rhythms of secretion Diurnal, pulsatile and cyclic and patterns

depend upon circulating substances

◦ Operate within feedback systems (+/-)

◦ Affect only target cells with appropriate receptors

◦ The liver inactivates hormones, rendering the hormones more water soluble for renal excretion

Regulation of Hormone Release

• Hormones are released:– In response to an alteration in the cellular

environment– To maintain a regulated level of certain

substances or other hormones

• Mechanism – release– Chemical factors (blood sugar , Ca++ levels)– Endocrine factors (FSH → ovary → E)–Neural control (CRF → pituitary → ACTH)

Feedback

Hormone Transport (Table 17-1) Hormones are released into the

circulatory system by endocrine glands

◦Water-soluble hormones circulate in free unbound forms Short-acting responses Bind to surface receptors

◦Lipid-soluble hormones are

primarily circulating bound to a carrier (Table 17-2) Rapid and long-lasting response Bind to cytoplasm or nucleoplasm receptor

Cellular Mechanisms of Hormone Action

Target cell – recognize, bind and initiate

Up – regulation

Down – regulation

Hormone effects◦Direct – stimulation

◦Permissive – facilitates maximum response/function

Cellular Mechanisms of Hormone Action

Hormone receptors◦ Located in the plasma membrane or in the

intracellular compartment of the target cell

Water-soluble hormones (peptides)◦ High molecular weight

◦Cannot diffuse across the plasma membrane

Cellular Mechanisms of Hormone Action

Lipid-soluble hormones

◦ Easily diffuse across the plasma membrane and bind to cytoplasm or nuclear receptors

Cellular Mechanisms of Hormone Action

Water-soluble hormones◦First messenger

Signal transduction

◦Second messenger molecule (Table 17-3) Calcium Cyclic adenosine monophosphate (cAMP) Cyclic guanosine monophosphate (cGMP) Tyrosine kinase system

Cellular Mechanisms of Hormone Action

Lipid-soluble hormones◦Steroid hormones

Androgens, estrogens, progestins, glucocorticoids, mineralocorticoids, thyroid hormones, vitamin D, retinoid

◦ Diffuse across the plasma membrane Bind to cytoplasmic or nuclear receptors Activate DNA transcriptn and translation

Steroid Hormone Mechanism

Structure and Function of the Endocrine Glands

• Hypothalamus• Pituitary gland

–Anterior pituitary (adenohypophysis)

A) Chromophobes – non-secretory cellsB) Chromophils - secretory cells

7 cell types → specific hormones

Structure and Function of the Endocrine Glands

Pituitary gland◦Posterior pituitary (neurohypophysis) Synthesized with binding proteins in the neurons of the supraoptic and paraventricular nuclei of the hypothalamus → stored

Anti-diuretic hormone (ADH) Oxytocin

Control of Posterior Pituitary Hormones

Release (both)◦Stimulation of cholinergic receptors by Ach, angiotensin II, and B-endorphins

Inhibition◦B-adrenergic receptors

Posterior Pituitary• Anti-diuretic hormone– Controls plasma osmolality –↑ permeability of distal renal tubules and

collecting ducts– Pharmacological levels ADH (vasopressin) →

vasoconstriction and ↑ BP–Regulation • Osmoreceptors of the hypothalamus

• Baroreceptors: L atrium, carotid and aortic arches (intravascular volume) also: stress, trauma, pain, exercise, nausea, nicotine, heat, morphine → ↑ secretion, ↓ HTN, alcohol and ↑ plasma volume

Oxytocin◦ Uterine contractions and milk ejection with

lactation

◦ Role in sperm motility in men

◦ ADH effect-weak

Thyroid Gland“controls the rate of metabolic

processes”• Bilobed either side of trachea – joined by

isthmus• Follicles – follicle cells surrounding colloid• Parafollicular cells (C cells)– Secrete calcitonin (↓ serum Ca++ by # bone –

resorption)• Regulation– Thyrotropin – releasing hormone and thyroid

stimulating hormone

Thyroid Gland Thyroid hormones

◦ Iodine – required for synthesis◦90% T4 and 10% T3

◦Bound to thyroxine - binding globulin - mostly

◦Regulation - negative feedback TRH - ↑ cold exposure, stress and ↓ T4

◦Effects ↑ metabolism of protein, fat and glucose →

rapid ↑ heat production and body temperature Normal linear growth requires TH CNS and ANS require TH

Parathyroid Glands Parathyroid hormone

◦ ↑ Ca++ and↓ PO4= - bone, kidneys

◦ Antagonist of calcitonin

Endocrine Pancreas The pancreas is both an endocrine and an

exocrine gland Islets of Langerhans

◦ Secretion of glucagon and insulin◦ Cells

Alpha – glucagon Beta – insulin Delta – somatostatin and gastrin F cells – pancreatic polypeptide

Endocrine PancreasInsulin

◦ Synthesized from proinsulin◦ Secretion is promoted by ↑ blood glucose◦ Facilitates the rate of glucose uptake into

the cells◦ Anabolic hormone

Synthesis of proteins, lipids and nucleic acids

Endocrine PancreasGlucagon

◦ Secretion is promoted by decreased blood glucose levels

◦ Stimulates glycogenolysis, gluconeogenesis and lipolysis

Somatostatin (delta cells)◦ Regulation alpha and beta cell secretions

Adrenal Glands Adrenal cortex

◦ 80% of an adrenal gland’s total weight

◦ Zona glomerulosa – aldosterone 15%◦ Zona fasciculata – glucocorticoids 78%◦ Zona reticularis – androgens and estrogens

(others) ◦ 7%

Adrenal medulla◦ Innervation by SNS

Adrenal Cortex“all hormones derived from cholesterol”

Stimulated by adrenocorticotropic hormone (ACTH)

Glucocorticoid hormones◦ Direct effect on carbohydrate metabolism◦ Anti-inflammatory and growth suppression

effects◦ Influences awareness and sleep habits◦ Inhibits bone matrix-protein matrix

◦Cortisol – most potent naturally occurring

Hypothalamus

Anterior pituitary

Adrenal cortex

Corticotropin-releasing factor (CRF)

Adrenocorticotropic hormone (ACTH)

Glucocorticoids(especially cortisol)

HypoxiaHypoglycemiaHyperthermiaExerciseCortisol insufficiency

Stress

Diurnal rhythms

( - )

SomatostatinHypothalamic lesions

( - )

(+)

(+)

(+)

Adrenal Cortex Mineralocorticoid hormones – Aldosterone

◦ ↑ Na+ uptake in epithelial cells – distal nephrons

◦ ↑ Na retention with loss of K+ and H+

◦ Regulation by the renin-angiotensin system

Na+ and H2O depletion ↑ K+ excreteion ↓ blood volume

Adrenal Cortex Adrenal estrogens and androgens

◦Estrogen secretion is minimal (vs. ovary)

◦Androgens – weak Converted by peripheral tissues to stronger

androgens such as testosterone

Adrenal Medulla Chromaffin cells (pheochromocytes)

◦ Secrete catecholamines – epinephrine and norepinephrine

◦“Fight or Flight Response” SNS, hypoglycemia, hypoxia, hypercapnia,

acidosis, hemorrhage, glucagon, nicotine, pilocarpine, histamine and angiotensin II

◦ Epinephrine is 10x more potent than NE◦ Promote hyperglycemia