1. UNIVERSIDAD CENTRAL DE VENEZUELA
FACULTAD DE MEDICINA
ESCUELA DE MEDICINA “LUIS RAZETTI”
CÁTEDRA DE FISIOLOGIA
Emilia Díaz
1 de marzo 2012
2. Glucocorticoides.
Anatomía de las glándulas suprarrenales.
Estructura, síntesis, y secreción del cortisol.
Ritmo circadiano.
El eje hipotálamo-hipófisis-adrenal: CRH, ACTH.
Transporte del cortisol en la circulación.
Productos de degradación del cortisol.
Mecanismo de acción: receptores nucleares, transducción de la
señal. Efectos genómicos y no genómicos
Efectos fisiológicos del cortisol. Efectos permisivos. Interacción con
otras hormonas.
CONTENIDO PROGRAMÁTICO
18. • 41 aa
• Vida media larga:26 min
• Potencian su secreción:ADH y angiotensina II
• Inhiben su secreción: oxitocina y ACTH
• Neuronas CRH:núcleo paraventricular con extensión
a la eminencia media
• También es producida por la placenta
• Sus niveles aumentan al final del embarazo y en el
parto
27. All steroid hormone receptors,
except for the estrogen receptor
(ER), bind to the double-stranded
DNA sequence AGAACA
Structural basis of nuclear receptor (NR)
DNA-binding specificity.
31. Efectos genomicos de los glucocorticoides incluyendo la transactivation y la
transrepresion
Stahn C and Buttgereit F (2008)
34. Regulation of tissue GR activity by distinct signaling pathways
Ann N Y Acad Sci. 2009 October ; 1179: 153–166. doi:10.1111/j.1749-6632.2009.04988.x.
37. Efectos el metabolismo del cortisol sobre el metabolismo de
los carbohidratos y proteinas en el hìgado
39. Arthritis specialists (left to right) Dr. C. H. Slocumb,
Dr. Edward C. Kendall, Dr. Philip S. Hench, and Dr. H. F.
Polley examining a patient at the Mayo Clinic.
“In 1950, Philip S. Hench
and his co-workers
Edward Kendall and
Tadeus Reichstein
received the Nobel Prize
for medicine for their
landmark discovery of
glucocorticoids and the
beneficial effects in
rheumatoid arthritis ”.
http://www.the-rheumatologist.org/details/article/984173/Chronotherapy_with_Glucorticoids_in_Rheumatoid_Arthritis.ht
40. CELL TYPE FACTOR COMMENTS
Macrophages and
monocytes
Arachidonic acid and its metabolites
(prostaglandins and leukotrienes)
Mediated by glucocorticoid inhibition of
cyclooxygenase-2 and phospholipase A2.
Cytokines, including: interleukin (IL)-1, IL-
6, and tumor necrosis factor-α (TNF-α)
Production and release are blocked. The cytokines
exert multiple effects on inflammation (e.g.,
activation of T cells, stimulation of fibroblast
proliferation).
Acute phase reactants These include the third component of complement.
Endothelial cells Endothelial leukocyte adhesion molecule-1
(ELAM-1) and intracellular adhesion
molecule-1 (ICAM-1)
ELAM-1 and ICAM-1 are intracellular adhesion
molecules that are critical for leukocyte localization.
Acute phase reactants Same as above, for macrophages and monocytes.
Cytokines (e.g., IL-1) Same as above, for macrophages and monocytes.
Arachidonic acid derivatives Same as above, for macrophages and monocytes.
Basophils Histamine, leukotriene C4 IgE-dependent release inhibited by glucocorticoids.
Fibroblasts Arachidonic acid metabolites Same as above for macrophages and monocytes.
Glucocorticoids also suppress growth factor-induced
DNA synthesis and fibroblast proliferation.
Lymphocytes Cytokines (IL-1, IL-2, IL-3, IL-6, TNF-α, GM-
CSF, interferon-γ)
Same as above for macrophages and monocytes.
Goodman & Gilman's The Pharmacologic Basis of Therapeutics - 11th Ed. (2006
Effects of Glucocorticoids on Components of Inflammatory/Immune Responses
42. 1. Inhibición de fibroblastos, colágeno y tejido
Conectivo
2. Inhibición de formación ósea
3. Estimulación de resorción ósea (aumenta excreción
de hidroxiprolina)
4. Potencia acción de PTH y Vitamina D3 en el hueso
5. Reduce absorción intestinal de calcio
6. Aumenta excreción urinaria de calcio
45. 1. Inhibición farmacológica de TRH, TSH y T4
2. Inhibición farmacológica de LH y rpta de LH a
GnRH
3. Incrementa tono intraocular (dosis
farmacológica)
49. Table 59-1. Normal Daily Production Rates
and Circulating Levels of the Predominant
Corticosteroids
CORTISOLALDOSTERONE
Rate of secretion under optimal conditions
10 mg/day 0.125 mg/day
Concentration in peripheral plasma:
8 A.M. 16 ug/100 ml 0.01 ug/100 ml
4 P.M. 4 ug/100 ml 0.01 ug/100 ml
53. The episodic, pulsatile pattern of ACTH secretion and its concordance with cortisol secretion in
a healthy human subject during the early morning.
(Reproduced, with permission, from Gallagher TF et al: ACTH and cortisol secretory patterns in
man. J Clin Endocrinol Metab 1973;36:1058.)
61. Figure 1 One gene encodes different receptor variants
Stahn C and Buttgereit F (2008) Genomic and nongenomic effects of glucocorticoids
Nat Clin Pract Rheumatol doi:10.1038/ncprheum0898
64. NEFAs: non-esterified (or free) fatty acids are a major source of fuel for
oxidative metabolism
Musculo cardíaco y esquelético
período postabsortivo
TAG:
triacylglycerides