Mechanisms of Hormonal Regulation

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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 Ac t ion

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 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% T

4 and 10% T

3

◦ Bound to mostly thyroxine - binding globulin -

◦ Regulation negative feedback

 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↓ PO

4

= - 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

(+)

Stres s

Hypoxia

(+)

Hypoglycemia

Hyperthermia

Exercise

Cortisol insufficiency

(+)

Hypothalamus

Corticotropin-releasing factor

(CRF)

Anterior pituitary

Adrenocorticotropic hormone

(ACTH)

Diurnal rhythms

( - )

( - )

Somatostatin

Hypothalamic lesions

Adrenal cortex

Glucocorticoids

(especially cortisol)

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 H

2

O 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

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