STEROIDS & STEROID

ABUSE
BIO1206 L6
 COMMONWEALTH OF AUSTRALIA

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 REFERENCES:
Bullock and Manias (2014) Fundamentals of Pharmacology, 7th edition. Pearson
Australia Group
Hall (2011) Guyton & Hall Textbook of Medical Physiology, 12th edition. Elsevier, USA
Marieb & Hoehn (2016) Human Anatomy & Physiology, 10th edition. Pearson
Education Ltd
Rang, Ritter, Flower and Henderson (2016), Rang and Dales Pharmacology, 8th edn,
Elsevier Health Sciences (USQ online
https://www.clinicalkey.com.au/#!/browse/book/3-s2.0-C20120031079)
Silverthorn DU (2010) Human Physiology: An Integrated Approach, 5th edition.
Benjamin Cummings, San Francisco
Widmaier, Raff & Strang (2016) Vanders Human Physiology the Mechanisms of
Body Function, 14th edition. McGraw-Hill, NY
 TYPES & ROLES OF STEROID
HORMONES
Glucocorticoids (cortisol)
Gluconeogenesis, lipolysis, protein breakdown
Mineralocorticoids (aldosterone)
Blood volume and pressure maintenance
Androgens (testosterone)
Reproductive functionality, anabolic activity
Oestrogens (oestradiol, oestrone)
Reproductive functionality
Progestogens/progestins (progesterone)
Reproductive functionality
http://res.cloudinary.com/lw
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STEROID HORMONES
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esterol_fig1.jpg

Silverthorn (2013) fig 23.1

 REGULATION OF STEROIDS
Physiological
Synthesised and released when needed
Rate limited by enzymes for conversions
Sometimes secreted by one cell and converted to active in target cell
Negative feedback
Binding proteins/soluble receptors
Affinity for target cell receptor
Legal
Prescription from medical practitioner, dentist or veterinarian
 LICIT USES
Glucocorticoids
Anti-inflammatory,
Oestrogenic agents/modifiers
Breast cancer (tamoxifen)
Reproductive
Anabolic agents/ modifiers
Muscle growth, anabolic
Reproductive
 GLUCOCORTICOIDS AS ANTI-
INFLAMMATORIES
Metabolic and Immune actions:
Increase blood glucose, increase protein
catabolism, increase lipolysis
Potent immunosuppressants (inflammation,
immune disorders, organ transplants, lung
maturation for premature infants)
PLA2 inhibition due to increased synthesis of
Annexin-1 (intracellular mediator)
Inhibit activity of Phospholipase A2 (PLA2) and
Cyclo-oxygenase (COX), preventing synthesis
of key inflammatory and immune modulators
(eg eicosanoids, leukotrienes)

Bullock and Manias 2014 fig 41.1

 GLUCOCORTICOIDS AS ANTI-
INFLAMMATORIES
Potent immunosuppressants (inflammation, immune
disorders, organ transplants, lung maturation for
premature infants)
Decrease size of lymph nodes and spleen
Inhibit helper T cells, decrease neutrophil and
macrophage responsiveness
Stabilise mast cell membrane
Inhibit protein synthesis (decrease Ab and cytokine
production)
Decrease fibroblast activity, slowing healing process
Corticosteroids (Cortisol) increases tissue responsiveness to
catecholamines (increase SNS effects and may increase
tone of precapillary sphincters and endothelial cells)

Bullock and Manias 2014 fig 62.1

 OESTROGEN AND OESTROGEN
MODULATORS
Oestrogen normally found in the body (main source ovarian tissue)
Anabolic effects, stimulates renal Na+ reabsorption, inhibiting diuresis
Enhances HDL-C and decreases LDL-C
Promotes gynoid fat deposition
Stimulates long bone lengthening, feminisation of skeleton (eg bony pelvis)
Stimulates growth and maturation (internal and external genitalia, breasts)
Promotes proliferative phase of uterine cycle
Some cancers are oestrogen-dependant

Anti-oestrogenics can sometimes increase oestrogen! Really!

Anti-oestrogens block the oestrogen receptor and therefore decrease negative feedback
effect on oestrogen on FSH/LH,
Increased FSH/LH increases follicular development and increases oestrogen secretion in
ovaries
Selective oestrogen receptor modulators (SERMs) oestrogen-like effects in some tissues but anti-
oestrogen effects in others (eg Tamoxifen)
 ANABOLIC-ANDROGENIC STEROIDS
(AAS) AND MODULATORS
Anabolic agents promote growth and healing
Endogenous androgens (eg testosterone) have:
Anabolic effects on muscles, bone, skin
Androgenic effects on male secondary sex characteristics development (growth
development of male genitalia, spermatogenesis, body hair growth), brain function
and libido
Produced normally in males and females
men: T main secreted androgen (Leydig cells), early adulthood ~500-700 (up to 1100) ng/dL
and age 70+ ~ 90-890 ng/dL
women: T main androgen (CL & adrenal cortex), early adulthood peak ~ 30-50ng/dL
Can be used as treatment for hypogonadism, hypopituitarism, muscle wasting
Modulators in treatment of prostatic hypertrophy (eg 5-reductase inhibitors block
conversion of T to 5DHT which can decrease hypertrophy)
Antiandrogens can be used in prostate cancer treatment in men and in women for
treatment of hirsutism, amenorrhea, etc
 TESTOSTERONE DEFICIENCY
(HYPOGONADISM) IN MALES
3rd trimester (testicular disease or LH deficiency) microphallus and
undescended testes (cryptorchidism)
Before end of puberty
incomplete puberty (decrease in male secondary sex characteristics)
if GH secretion normal long bones continue to grow longer arms and legs
relative to trunk (eunuchoid)
Enlargement of glandular breast tissue (gynaecomastia)
After puberty complete and if severe reduction in T
libido and energy (weeks)
Hct and Hb (months)
bone mineral density and muscle mass (years)
 TREATMENT: MALE
HYPOGONADISM
Ingestion of T not effective as rapidly metabolised by liver
T delivered as:
Esters: dissolved in oil, IM fortnightly
Alkylated androgens: retards hepatic metabolism so per os 17-alkylated
androgens are androgenic (less than T and hepatotoxic)
Transdermal: (stable) T within normal range
 REVISION

Silverthorn 5th ed. Figure 26.13 Silverthorn 5th ed. Figure 26.10
 NON-THERAPEUTIC AAS USE
Anabolic-androgenic steroids (AAS)
Include testosterone and synthetic derivatives
Chronic use associated with:
many disorders (cardiovascular, endocrine, metabolic, neurologic, renal,
musculoskeletal) manifested as dyslipidaemia, cardiomyopathy, major mood
disorders, aggression, violence, cognitive dysfunction and dependence on AAS
early mortality
testicular atrophy, testicular fibrosis, azoospermia
Non-therapeutic uses include:
increasing muscle mass above that could be achieved without AAS
Improving performance
Improving strength and appearance
WHAT DO YOU NEED TO KNOW?