Glicocorticóide em gatos

Páginas: 29 (7168 palavras) Publicado: 3 de dezembro de 2012
DOI: 10.1111/j.1365-3164.2008.00717.x

Glucocorticoids in the cat
Blackwell Publishing Ltd

Andrew D. Lowe*, Karen L. Campbell† and
Thomas Graves†
*Fox Valley Animal Referral Center, Appleton, WI, USA
†Department of Veterinary Clinical Medicine, University of Illinois,
Urbana-Champaign, IL, USA
Correspondence: Andrew D. Lowe, Fox Valley Animal Referral Center,
Appleton, WI, USA.E-mail: drlowea@gmail.com
Sources of funding
Self-funded.
Conflict of interest
None.

Abstract
Glucocorticoids are one of the two main classes of
hormones, along with mineralocorticoids, which are
secreted from the adrenal cortex. Since the discovery
of the anti-inflammatory properties of the natural
glucocorticoid hydrocortisone, a large number of
artificial glucocorticoids have beensynthesized to
attempt to increase efficacy and decrease side effects.
These drugs are now considered one of the most
commonly prescribed agents in veterinary practice.
The effect of these drugs has been shown to vary
significantly between species. Cats appear to tolerate
glucocorticoids well, resulting in these drugs being
recommended for a wide variety of conditions; however,
there are few studieson the effects of glucocorticoids
in cats. In this paper we review some of the available
literature on glucocorticoid use in the cat.

Mechanism of action
GCs exert their effects through both genomic and nongenomic mechanisms. Genomic events involve binding of
a GC to an intracellular GC receptor (GR), located primarily
in the cytoplasm (Fig. 1). GRs are composed of three main
proteindomains – an amino-terminal domain with transcriptional activating properties, a central DNA-binding
domain containing two zinc fingers, and a carboxy-terminal
ligand-binding domain.1 On binding a GC ligand, the GR
disassociates from a series of chaperone proteins including
heat shock protein 90 (Hsp90), Hsp70, Hsp40, co-chaperone
p23 and immunophilins FKBP52 and Cyp40. Disassociation
from theseproteins was thought to expose nuclear
localization domains on the GR which, upon binding to
proteins known as importins, prompted the migration of
the ligand-bound GR into the nucleus.1 Recent work has
suggested that the binding of importins with GRs is
independent of GC binding, but that hormone binding
might affect downstream pathways.2 The protein 14-3-3
has been proposed as acytoplasmic tether for the GR in the
absence of GC, and release from 14-3-3 may be important in
GR migration.1
Regardless of whether it is required, transport of the GR
through the nuclear membrane is facilitated by ligand binding.

Accepted 29 May 2008

Introduction
Glucocorticoids (GCs) are among the most commonly
prescribed drugs in veterinary medicine. GCs exert a
broad range of activities,and have consequences on every
organ system. Cats are often considered less susceptible
to GC-induced side effects than other species. When
clinical signs do occur, however, they can be severe, and
can include marked cutaneous atrophy, skin fragility, congestive heart failure (CHF) and increased susceptibility to
diabetes mellitus (DM). Pharmacological studies evaluating
effects of GCs incats are lacking. Most of the currently
recommended GC dosing regimens for cats are extrapolated from human or canine studies and modified based on
clinical experience. Here we present a review of published
studies on GC use in the cat, as well as a basic review of
general GC pharmacology.
340

Figure 1. Mechanism of action of glucocorticoids. (1) Glucocorticoids
(GCs) enter the cell and bindto glucocorticoid receptors (GRs), which
are found primarily in the cytoplasm bound to chaperone proteins. (2)
Binding of a GC causes release of chaperone proteins and migration
of the GC–GR complex into the nucleus. (3) GC–GR complexes are
able to dimerize and bind to glucocorticoid response elements (GREs)
in the DNA. Binding to a positive GRE (pGRE) promotes transcription
while binding...
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