About steroids, steroid receptors, examples of steroid drugs

2.  Steroids/Steroid hormones are Lipophilic compounds
 They have low molecular weight
 Enters cell membrane through simple diffusion
 Parent compound- Cholesterol
 Contains Cyclopentophenathrene ring

3.  Steroids act on both the peripheral targets tissues and the central nervous system
 They are grouped into five different types based on the receptors to which they
bind
Glucocorticoids
Mineralocorticoids
Sex corticoids- Estrogen, Progesterone and Testosterone
• The adrenal corticoids like glucocorticoids and mineralocorticoids modulates
carbohydrate metabolism and acts as immunosuppressive and anti-inflammatory
components
• Sex corticoids or Gonadal steroids influence sexual differentiation and secondary
sexual characteristics of male and female

4.  Steroid receptors are proteins that have specific binding sites for steroids to bind
 They are found in both cytosol and in nucleus of the target cells
 These receptors belong to Nuclear Receptor Family
 Ligand activated proteins that regulates selected genes
 Response Element- DNA sequences to which this hormone-receptor complex is
bound

5.  Receptor contains 5 distinct regions
Two end terminals – N terminal & C terminal
Hinge region
Two domains- DNA binding domain and ligand binding domain

6. Steroid hormone enters
cell and binds to
receptor
Translocation of
activated receptor-ligand
complex into cell
Binds to another specific
receptor on the
chromatin
Steroid Receptor forms
dimer
Acts on DNA
Augmentation/Inhibition
of Transcription

8.  Two models describe how the Steroid Receptor-Ligand complex interacts with
DNA
1st Model:
In this model, when the receptor complex binds to DNA, the nucleosome wraps it
tightly. Acetylation of tail lysines of this nucleosomes makes the transcription factor
accessible. But nucleosome architecture is maintained
2nd model
In this model, a transient/unstable pore is created in the nucleosome to stabilize the
conformation of chromatin
 Regulation
The action of steroid hormones is regulated by the presence of two components-
Coactivators and Corepressors. They are important for transcription to occur

9.  It is a adrenocorticoid hormone
synthesized in the adrenal cortex
 They function by stimulating or inhibiting
some protein synthesis
 The adrenal cortex is composed of three
layers
outer zone (zona glomerulosa) produces
aldosterone (mineralocorticoid)
middle zone (zona fasciculata) produces
cortisol (glucocorticoid)
inner zone (zona reticularis) produces
androgens

10.  The glucocorticoids affect the metabolism of carbohydrates, proteins, fats, electrolytes,
water and calcium
 In pharmacological doses, glucocorticoids antagonise the action of vitamin D on the
gut and reduce absorption of calcium
 The cardiovascular changes which occur in adrenal insufficiency are partly due to
glucocorticoid deficiency
 Permissive concentration of cortisol is necessary for the normal functioning of the
skeletal muscle
 Glucocorticoid is used to treat Addison’s disease
 Glucocorticoids prevent or suppress the symptoms and signs of inflammation such as
local heat, redness, swelling and tenderness. They are potent anti-inflammatory agent

11. Glucocorticoids in large therapeutic doses(40-60 mg of prednisolone per day)-
 Inhibit the function of macrophages and reduce their ability to respond to antigens
 Inhibit the activation of cytotoxic T lymphocytes and their proliferation
 Cause lysis of the T lymphocytes
 Suppress cell-mediated hypersensitivity reaction
 Prevent Graft Rejection

12.  Cortisone
 Hydrocortisone
 Prednisolone
 Methylprednisolone
 Dexamethasone
 Betamethasone
 Triamcinolone

13.  Related to individual susceptibility , dosage and duration of therapy. Prolonged therapy
have adverse health effects
 Gastrointestinal tract: Acute erosive gastritis with hemorrhage may occur during
intensive therapy , and peptic ulceration may be troublesome during prolonged therapy
 Metabolic effects- Ketoacidosis, Hyperglycemic and Hyperosmolar Coma, hyperlipidemia
and hypophosphatemia
 Cushingoidism- Obesity with moon face and buffalo hump
 Suppression of inflammation and immune responses
 Retardation of linear growth occurs in children who receive high doses
 Cardiovascular and renal system: Hypertension, salt and water retention and rarely
hypokalemic alkalosis can occur
 CNS: Insomnia, Beningn Intracranial hypertension and aggravation of epilepsy
 Eyes: Glaucoma and Cataract

14.  A 55-year-old female patient presented to the emergency unit with a history of severe
breathlessness, productive cough with scanty white sputum and early morning wheeze since
two days.
 Asthmatic since 30 years. Past history revealed that eight years back she was prescribed
tablet betamethasone, 10 mg once a day for 10 days. She recovered and continued self
medication whenever required for 10 years
 Patient is diabetic from 7 years, works in a flour mill
 Diagnosis and lab investigation found that the patient have multiple steroid-induced
adverse effects like:
steroid induced-diabetes mellitus
Osteoporosis
 HPA axis suppression( Hypothalamo-pituitary-Adrenal) and
 cataract
Reference- Satyanarayanasetty, D., Pawar, K., Nadig, P., & Haran, A. (2015). Multiple
Adverse Effects of Systemic Corticosteroids: A Case Report. Journal of clinical and diagnostic
research : JCDR, 9(5), FD01–FD2. doi:10.7860/JCDR/2015/12110.5939