Genomic signaling
Genomic mechanisms, regardless of which type, elicit responses with a slow onset and a slow dissipation. This is attributed to the duration of mRNA transcription and translation. Glucocorticoids have the ability to regulate roughly 100 to 1000 genes with specificity to cell-type.Three major mechanisms have described how the MP-GR complex alter gene expression by either binding to DNA or transcription modulators. One mechanism of genomic signaling occurs when the MP-GR complex directly binds to DNA sequences called glucocorticoid response elements (GREs). GREs are located in regulatory regions of target genes and mediate their transactivation or transrepression. For example, the activation of lipocortin 1 (ANAX1) negatively interferes with the production of prostaglandins and leukotrienes, known pro-inflammatory signals. Likewise, negative GREs (nGREs) are responsible for repressing genes involved in immune cell activation. Post transcriptional  modifications
Post translational modifications (PTMs) also contribute to methylprednisolone signaling and can produce genomic and non-genomic effects. The GR has contains several sites for phosphorylation, sumoylation, ubiquitination, and acetylation that primarily occurs after intracellular methylprednisolone binding to the GR. PTMs modulate many functions including nuclear translocation, strength and duration of receptor signaling and cofactor interaction. A specific example is the deacetylation by histone deacetylase 2 (HDACe) was necessary for transrepression of  NF-κB. Non-genomic signaling
The mechanisms of non-genomic signaling are distinct from genomic signaling, yet mediate similar pathways and provide therapeutic relevance.
Trabecular bone loss in the lumbar spine precedes cortical bone loss in the femoral neck. Exhaustive list
Allergic: allergic or hypersensitivity reactions, anaphylactoid reaction, anaphylaxis, and urticaria.Cardiovascular: hypertension, congestive heart failure in susceptible patients, premature atherosclerotic disease, arrhythmias, and possible hyperlipidemia.Dermatologic: impaired wound healing, petechiae and ecchymoses, thinning of the skin, facial erythema, and increased sweating.Endocrine: Cushingoid features, growth suppression in children, secondary adrenocortical and pituitary unresponsiveness, menstrual irregularities, decreased carbohydrate intolerance, and latent diabetes mellitus. In patients with diabetes, increased requirements of insulin or oral hypoglycemic agents.Fluid and electrolyte disturbances: sodium retention, fluid retention, potassium loss, hypokalemic alkalosis, or congestive heart failure in susceptible patients.Gastrointestinal: peptic ulcer, pancreatitis, abdominal distention, and ulcerative esophagitis.Metabolic: protein catabolism which causes negative nitrogen balance.Musculoskeletal: muscle weakness, loss of muscle mass, steroid myopathy, osteoporosis, tendon rupture (especially Achilles), vertebral compression fractures, aseptic necrosis of femoral and humeral heads, and pathologic fracture of long bones.Neurological: increased intracranial pressure with papilledema, convulsions, vertigo, and headache.Ophthalmic: posterior sub-capsular cataracts, increased intraocular pressure, glaucoma, and exophthalmos. Withdrawal
Feedback of the exogenous glucocorticoids at the hypothalamic–pituitary–adrenal (HPA) axis inhibits the secretion of the corticotropin-releasing hormone (CRH) and the adrenocorticotropic hormone (ATCH) at the hypothalamus and pituitary glands, respectively. Prolonged suppression leads to inadequate responses to physical and emotional stresses, such as illness and trauma. Suppression of ATCH may result in adrenal hypoplasia or secondary adrenal gland atrophy within 6 weeks of methylprednisolone therapy, leaving a patient at risk for developing life-threatening adrenal insufficiency crisis.