The endocrine system -- a brief overview.

I.  Introduction

-  the endocrine system is an integration system that influences the metabolic activities of cells.

-  acts via hormones, chemical messengers produced by endocrine glands -- pineal, hypothalamus, pituitary, thyroid, parathyroid, adrenals, pancreas, gonads.

-  endocrine system (ES) vs. nervous system (NS):

-  ES slow acting, long-term effects, metabolic regulation, water and electrolyte balance, nutrient balance, regulation of cell metabolism, energy balance.

II.  Hormones

- chemical substances secreted by cells into ECFs that regulate metabolic function of other cells.

A.  Chemistry

1.  amino aid based hormones:  amino acid derivatives, single modified amino acids, peptides, proteins, glycoproteins.

2.  steroid based hormones - cholesterol derivatives.

3.  eicosanoids -- derivatives of 20-carbon polyunsaturated fatty acid, arachidonic acid

• arachidonic acid is fatty acid found in membrane of all cells
• include prostaglandins, prostacyclins, thromboxanes, leukotrienes
• extremely active biologically
  • smooth muscle contraction (prostaglandins), relaxation (prostacyclins)
  • clot formation:
    • stimulate platelet aggregation (thromboxane)
    • inhibit platelet aggregation (prostacyclin)
  • mediator of allergic and inflammatory response:
    • leukotrienes:
      • bronchoconstriction
      • arteriolar vasodilation
      • increased vascular permeability
      • chemotaxic:  attract WBC

B.  Mechanisms of hormone action

- hormones produce effects on target cells by:

- changes in membrane permeability due to opening/closing of channels.

- activation/deactivation of regulatory molecules -- covalent modification.

- synthesis of regulatory molecules -- involves changes in gene expression.

-  these effects result in physiological changes:

- induction of secretory activity.

- stimulation of mitosis.

- contraction/relaxation

1.  Action of peptide/protein hormones

• hormones non-lipid soluble
• bind a membrane receptor molecule
• activation of G-protein
  • opens channel
  • activates enzyme
    • second messenager produced (cAMP, Ca⁺⁺)
    • second messenger initiates an intracellular cascade of events that bring about changes in cell function

2.  Action of steroid hormones

-  hormones are lipid soluble, pass through the cell membrane.

-  bind a cytosolic/nuclear receptor -- forms HR complex.

-  HR complex binds a chromatin site, changes shape of chromatin, exposes binding sites for transcription factors  -- transcription of a specific gene stimulated, new proteins synthesized.

C.  Hormone target cell specificity:  hormones produce effects in target cells that have receptors for hormone

-  target cell activation depends on:

• level of hormone present
• number of receptors for hormone
  • upregulation/downregulation of receptors
• affinity of receptor for hormone

D. Duration of hormone activity

-  depends on:

• rate of release vs. rate of degradation/excretion (measured by half life)
  • peptides have short half life, steroids have longer half life.
• degree of plama protein binding -- in case of lipid hormones

-  effects can last seconds to hours/days depending on hormone and mechanism of action.

E.  Control of hormone release

-  regulation in majority of cases via negative feedback.

-  cells stimulated to release hormones by three types of stimuli:

-  humoral stimuli

-  neural stimuli

-  hormonal stimuli.

III.  Major endocrine organs

A.  The pituitary gland

1.  Functional anatomy of pituitary-hypothalamic interactions.

1. pituitary (anterior/posterior) closely associated with hypothalamus via a stalk, infundibulum.
2. two two interconnected capillary beds, one in infundibulum a second bed associated with anterior/posterior pituitary.
3. anterior pituitary -- glandular epithelium; manufactures, releases a number of hormones; AP hormones released in response to presence of releasing hormones produced by neurons in the hypothalamus and released into the capillary bed of the infundibulum.
4. posterior pituitary -- neural tissue, neuron endings; stores and releases neurohormones that are synthesized in the cell bodies of its neurons in the hypothalamus; when neurons are activated, hormones released at posterior pituitary.

2.  Adenohypophyseal hormones (AP)

- secretion under influence of hypothalamic releasing hormones.

- four of adenohypophyseal hormones are tropic hormones -- regulate secretory activity of other endocrine glands (ACTH, FSH, LH, TSH).

- other two hormones exert their influence on non-endocrine targets -  GH, prolactin.

a.  growth hormone (GH)

-protein.

- stimulates virtually all cells of body to increase in size and divide, but main targets are bones (stimulation of epiphyseal plate growth) and skeletal muscle (stimulate increase in muscle mass).

- stimulates increased amino acid uptake from blood; mobilizes fats; spares glucose.

b.  thyroid-stimulating hormone (TSH)

-  glycoprotein.

-  stimulates normal development and secretory activity of the thyroid.

c.  adrenocorticotropic hormone (ACTH)

-  peptide.

-  stimulates the adrenal cortex to release glucocorticoids and androgens (corticosteroids).

d.  gonadotropins (FSH, LH)

-  glycoproteins.

-  FSH stimulates gamete production, LH stimulates productions of gonadal hormones.

e.  prolactin

-  protein.

-  stimulates milk production by breast secretory tissue.

3.  Neurohypophyseal hormones (PP)

a.  antidiuretic hormone (ADH)

-  peptide

-  firing of hypothalamic neurons that store ADH at their terminal endings stimulated by increased osmolarity of blood.

-  regulation of water balance, plasma volume.

b.  oxytocin

- peptide

-  stimulated by impulses from hypothalamic neurons in response to cervical/uterine stretching and suckling of infant at breast.

-  childbirth,; suckling reflex.

B.  Thyroid gland

-  largest endocrine gland, inferior to larynx.

1.  internal anatomy

- thyroid composed of follicles

- follicular cells secrete large glycoprotein, thyroglobulin to follicular space, and pump iodide into follicular space; thus follicular space contains thick proteinaceous material, colloid, the major component of which is thyroglobulin.

-  thyroglobulin contains many tyrosines -- iodination and coupling of tyrosine residues involved in formation of thyroid hormones.

2.  synthesis of thyroid hormones 

a.  synthesis/secretion of thyroglobulin to follicle

b.  iodide trapping, oxidation to iodine -- to lumen of follicle.

c.  iodination of tyrosines of thyroglobulin (MIT, DIT)

d.  coupling of iodinated tyrosines (T3/T4)

e.  colloid endocytosis -- iodinated thyroglobulin taken into cell.

d.  cleavage of thyroglobulin by lysosomal enzymes -- T3 and T4 released (modified amino acids).

3.  TSH stimulates all above steps; an enzyme critical for iodide trapping, iodination, and coupling is thyroid peroxidase.

4.  T3 and T4 are transported bound to plasma proteins, only a small amount of hormone is free in plasma; this protects hormones from degradation and provides body with a pool of ready to use thyroid hormone.

5.  Target tissues convert T4 to T3 -- hormone finally acting on tissues is T3.

6.  T3 acts via nuclear receptor model of steroid hormones.

7.  Effects of thyroid hormone

a.  promotes normal oxygen consumption and BMR -- by stimulating enzymes concerned with glucose oxidation.

b.  due to effects above it increases body heat production - calorigenic effect

-  modulates normal tissue growth and development.

C.  Parathyroid glands and parafollicular cells of thyroid

-  parathyroid glands synthesize and release parathyroid hormone; parafollicular cells of thyroid synthesize and release calcitonin.

-  calcium metabolism.

D.  Adrenal glands

1.  Adrenal cortex -- outer layer of adrenal gland, produces corticosteroids

a.  zona glomerulosa (outer cortex)

- mineralocorticoids -- aldosterone; role in electrolyte balance.

b.  zona fasciculata (middle cortex)

-  glucocorticoids -- cortisone, cortisol, hydrocortisone;  essential effects on carbohydrate metabolism, maintenance of blood volume, stress response, depress immune system.

c.  zona reticularis (inner cortex)

- androgens -- androstenedione, estrogens; onset of puberty, appearance of axillary and pubic hair.

2.  Adrenal medulla -- a sympathetic "ganglion"; epinephrine, norepinephrine.

E.  Pancreas - insulin and glucagon

F.  Gonads -- sex hormones, estrogen, progesterone, testosterone.