Download Mechanisms of Hormonal Regulation

Chapter 17
The Endocrine System
 Functions
◦ 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
Hormones
 General
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
(peptides)
hormones
◦ 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 cells
B) 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 Bendorphins

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
mostly
◦ Regulation - negative feedback
globulin -
 TRH - ↑ cold exposure, stress and ↓ T 4
◦ 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 Pancreas
 Insulin
◦
◦
◦
◦
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 Pancreas
 Glucagon
◦ 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
(+)
Diurnal
rhythms
(-)
Hypothalamus
Corticotropin-releasing factor
(CRF)
Stres
s
(+)
(+)
Hypoxia
Hypoglycemia
Hyperthermia
Exercise
Cortisol
insufficiency
(-)
Anterior pituitary
Adrenocorticotropic hormone
(ACTH)
Adrenal cortex
Glucocorticoids
(especially cortisol)
Somatostatin
Hypothalamic
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