A 22-year old male bodybuilder has come to the hospital because he believes his testicles are less than half their original size. He is worried that they will continue to shrink and affect his fertility and sex drive. Patient admits to injecting himself with anabolic steroids over the last few months. He would like to know what caused the shrinkage and what other side effects he could experience.

Upstream causes

Anabolic steroid use

Elevated levels of testosterone cause the brain to send signals that tell testicles to stop producing testosterone.

Background information

General functions of the Endocrine System

secrets hormones directly into the bloodstream

Regulates development, growth and metabolism

Maintains homeostasis of blood composition and volume

Controls digestive process

Controls reproductive activities

The two types of hormones

Water-soluble Hormones

Lipid-Soluble Hormones

Steroids

formed from cholesterol

Proteins

Biogenic amines (except thyroid hormone)

made of amino-acid chains

derived from amino-acid that is modified

Interaction with target cells

diffuse across plasma membrane

bind to intracellular receptors located in cytosol or nucleus

forms hormone-receptor complex

hormone-receptor complex formed with target cell binds to DNA sequence in regions of chromatin call hormone-response elements

transcription of mRNA occurs

translation occurs

change results in either an alteration of cell structure

or a shift in target cells' metabolic activities

Interaction with target cells

unable to cross plasma membrane

hormone binds to plasma membrane receptor

series of biochemical events occur across membrane called signal transduction pathway

the hormone becomes the first messenger

binding to the receptor becomes the second messenger

the second messenger modifies some cellular activity

The Major Endocrine glands

Pituitary gland

Pineal gland

melatonin

regulates sleep-wake cycle

Thyroid gland

T3- Triiodothyronine and T4- Tetraiodothyronine

increases metabolic rate

calcitonin

decreases blood calcium levels

Parathyroid gland

parathyroid hormone

increases blood calcium levels

Adrenal gland

Adrenal cortex

Aldosterone

Feedback loop concept

Negative feedback loop

a stimulus causes an action in the body that is the opposite of the stimulus

Positive feedback loop

a stimulus is reinforced to continue in the same direction

Up and down-regulation

Up-regulation

The process in which a target cell increases the amount of receptors

prevents understimulation

helps to maintain a normal cellular response

Down-regulation

The process in which a target cell decreases the amount of receptors it has

prevents over-stimulation

helps to maintain a normal cellular response

Downstream effects

With continued use of anabolic steroids

Kidney problems or failure

Liver damage or tumors

Enlarged heart

High blood pressure

Changes in blood cholesterol

Increased risk of heart attack or stroke

can lead to build up of plaque in the blood vessels

increased risk of heart attack

increased risk of stroke

increased risk of peripheral artery disease

can lead to the kidneys not working at all

body fills with extra water and waste

can cause seizures or coma

liver becomes inflamed

fibrosis occurs

diminished blood flow

cirrhosis occurs

complete liver failure

liver cancer

heart has to work harder to pump blood

can lead to heart attack

heart muscles become weak

can lead to heart disease and stroke

Sex drive can be effected

increased sex drive

decreased sex drive

erection problems

may cause fertility problems

decreased or stopped sperm production

With discontinued use of anabolic steroids

May experience withdrawal symptoms

mood swings

restlessness

loss of appetite

craving for steroids

feelings of anxiety or apathy

Sperm production normalizes after a year

Testicles begin to regenerate lost tissue

liver damage usually reverses

limited or no production of testosterone causes testicular shrinkage

Reasons for patient to abuse steroids

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Other potential effects

hair loss

development of breast

organ damage

infertility

wanted to gain more muscle mass

other body builders use steroids

pressure to meet personal goals

Patient experienced plateau with current muscle gain

regulates blood Na+ and K+ levels

Cortisol

stress response

Androgen

maturation of reproductive system

Adrenal medulla

Epinephrine and norepinephrine

fight or flight response

Pituitary gland (anterior)

Follicle-stimulating hormone

controls development of both ooctye and ovarian follicle within ovaries

Pituitary gland (posterior)

Antidiuretic Hormone

decreases urine output

Oxytocin

contraction of smooth muscle in the uterus

Luteinizing hormone

induces ovulation

Andrenocorticotropic hormone

stimulates adrenal cortex to release cortisol

Thyroid-stimulating hormone

stimulates thyroid gland to release thyroid hormone

Prolactin

regulates mammary gland growth

Growth hormone

induces growth

Feedback loop at work and its effects

continued use of steroids causes a negative feedback loop

this tells the brain to stop producing testosterone because of high levels

elevated levels of testosterone also cause down regulation of the receptors

Specific hormonal pathway from hypothalamus to testes

Hypothalamus releases Gonadotropin-releasing hormone (GnRH)

GnRH stimulates anterior pituitary

FSH(follicle-stimulating hormone) and LH (luteinizing hormone) are released

these hormones act on gonads to stimulate development of sperm and cause the testes to release testosterone